Publications by authors named "John M Johnson"

38 Publications

Skin vasoconstriction as a heat conservation thermoeffector.

Handb Clin Neurol 2018 ;156:175-192

Department of Physiology, University of Texas Health Center at San Antonio, San Antonio, TX, United States; Department of Medicine, University of Texas Health Center at San Antonio, San Antonio, TX, United States.

Cold exposure stimulates heat production and conservation to protect internal temperature. Heat conservation is brought about via reductions in skin blood flow. The focus, here, is an exploration of the mechanisms, particularly in humans, leading to that cutaneous vasoconstriction. Local skin cooling has several effects: (1) reduction of tonic nitric oxide formation by inhibiting nitric oxide synthase and element(s) downstream of the enzyme, which removes tonic vasodilator effects, yielding a relative vasoconstriction; (2) translocation of intracellular alpha-2c adrenoceptors to the vascular smooth-muscle cell membrane, enhancing adrenergic vasoconstriction; (3) increased norepinephrine release from vasoconstrictor nerves; and (4) cold-induced vasodilation, seen more clearly in anastomoses-rich glabrous skin. Cold-induced vasodilation occurs in nonglabrous skin when nitric oxide synthase or sympathetic function is blocked. Reflex responses to general body cooling complement these local effects. Sympathetic excitation leads to the increased release of norepinephrine and its cotransmitter neuropeptide Y, each of which contributes significantly to the vasoconstriction. The contributions of these two transmitters vary with aging, disease and, in women, reproductive hormone status. Interaction between local and reflex mechanisms is in part through effects on baseline and in part through removal of the inhibitory effects of nitric oxide on adrenergic vasoconstriction.
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http://dx.doi.org/10.1016/B978-0-444-63912-7.00011-4DOI Listing
March 2019

Responses to hyperthermia. Optimizing heat dissipation by convection and evaporation: Neural control of skin blood flow and sweating in humans.

Auton Neurosci 2016 04 21;196:25-36. Epub 2016 Jan 21.

Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78229-3901, United States.

Under normothermic, resting conditions, humans dissipate heat from the body at a rate approximately equal to heat production. Small discrepancies between heat production and heat elimination would, over time, lead to significant changes in heat storage and body temperature. When heat production or environmental temperature is high the challenge of maintaining heat balance is much greater. This matching of heat elimination with heat production is a function of the skin circulation facilitating heat transport to the body surface and sweating, enabling evaporative heat loss. These processes are manifestations of the autonomic control of cutaneous vasomotor and sudomotor functions and form the basis of this review. We focus on these systems in the responses to hyperthermia. In particular, the cutaneous vascular responses to heat stress and the current understanding of the neurovascular mechanisms involved. The available research regarding cutaneous active vasodilation and vasoconstriction is highlighted, with emphasis on active vasodilation as a major responder to heat stress. Involvement of the vasoconstrictor and active vasodilator controls of the skin circulation in the context of heat stress and nonthermoregulatory reflexes (blood pressure, exercise) are also considered. Autonomic involvement in the cutaneous vascular responses to direct heating and cooling of the skin are also discussed. We examine the autonomic control of sweating, including cholinergic and noncholinergic mechanisms, the local control of sweating, thermoregulatory and nonthermoregulatory reflex control and the possible relationship between sudomotor and cutaneous vasodilator function. Finally, we comment on the clinical relevance of these control schemes in conditions of autonomic dysfunction.
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http://dx.doi.org/10.1016/j.autneu.2016.01.002DOI Listing
April 2016

Effect of skin temperature on cutaneous vasodilator response to the β-adrenergic agonist isoproterenol.

J Appl Physiol (1985) 2015 Apr 19;118(7):898-903. Epub 2015 Feb 19.

Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas; and.

The vascular response to local skin cooling is dependent in part on a cold-induced translocation of α2C-receptors and an increased α-adrenoreceptor function. To discover whether β-adrenergic function might contribute, we examined whether β-receptor sensitivity to the β-agonist isoproterenol was affected by local skin temperature. In seven healthy volunteers, skin blood flow was measured from the forearm by laser-Doppler flowmetry and blood pressure was measured by finger photoplethysmography. Data were expressed as cutaneous vascular conductance (CVC; laser-Doppler flux/mean arterial blood pressure). Pharmacological agents were administered via intradermal microdialysis. We prepared four skin sites: one site was maintained at a thermoneutral temperature of 34°C (32 ± 10%CVCmax) one site was heated to 39°C (38 ± 11%CVCmax); and two sites were cooled, one to 29°C (22 ± 7%CVCmax) and the other 24°C (16 ± 4%CVCmax). After 20 min at these temperatures to allow stabilization of skin blood flow, isoproterenol was perfused in concentrations of 10, 30, 100, and 300 μM. Each concentration was perfused for 15 min. Relative to the CVC responses to isoproterenol at the thermoneutral skin temperature (34°C) (+21 ± 10%max), low skin temperatures reduced (at 29°C) (+17 ± 6%max) or abolished (at 24°C) (+1 ± 5%max) the vasodilator response, and warm (39°C) skin temperatures enhanced the vasodilator response (+40 ± 9%max) to isoproterenol. These data indicate that β-adrenergic function was influenced by local skin temperature. This finding raises the possibility that a part of the vasoconstrictor response to direct skin cooling could include reduced background β-receptor mediated vasodilation.
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http://dx.doi.org/10.1152/japplphysiol.01071.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385879PMC
April 2015

Cutaneous vasodilator and vasoconstrictor mechanisms in temperature regulation.

Compr Physiol 2014 Jan;4(1):33-89

Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.

In this review, we focus on significant developments in our understanding of the mechanisms that control the cutaneous vasculature in humans, with emphasis on the literature of the last half-century. To provide a background for subsequent sections, we review methods of measurement and techniques of importance in elucidating control mechanisms for studying skin blood flow. In addition, the anatomy of the skin relevant to its thermoregulatory function is outlined. The mechanisms by which sympathetic nerves mediate cutaneous active vasodilation during whole body heating and cutaneous vasoconstriction during whole body cooling are reviewed, including discussions of mechanisms involving cotransmission, NO, and other effectors. Current concepts for the mechanisms that effect local cutaneous vascular responses to local skin warming and cooling are examined, including the roles of temperature sensitive afferent neurons as well as NO and other mediators. Factors that can modulate control mechanisms of the cutaneous vasculature, such as gender, aging, and clinical conditions, are discussed, as are nonthermoregulatory reflex modifiers of thermoregulatory cutaneous vascular responses.
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http://dx.doi.org/10.1002/cphy.c130015DOI Listing
January 2014

Nitric oxide and receptors for VIP and PACAP in cutaneous active vasodilation during heat stress in humans.

J Appl Physiol (1985) 2012 Nov 6;113(10):1512-8. Epub 2012 Sep 6.

Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs, South Texas Veterans Health Care System, Audie L. Murphy Memorial Veterans Hospital Division, San Antonio, TX 78229, USA.

VPAC2 receptors sensitive to vasoactive intestinal polypeptide (VIP) and pituitary adenylyl cyclase activating polypeptide (PACAP), PAC1 receptors sensitive to PACAP, and nitric oxide (NO) generation by NO synthase (NOS) are all implicated in cutaneous active vasodilation (AVD) through incompletely defined mechanisms. We hypothesized that VPAC2/PAC1 receptor activation and NO are synergistic and interdependent in AVD and tested our hypothesis by examining the effects of VPAC2/PAC1 receptor blockade with and without NOS inhibition during heat stress. The VPAC2/PAC1 antagonist, pituitary adenylate cyclase activating peptide 6-38 (PACAP6-38) and the NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME) were administered by intradermal microdialysis. PACAP6-38, l-NAME, a combination of PACAP6-38 and l-NAME, or Ringer's solution alone were perfused at four separate sites. Skin blood flow was monitored by laser-Doppler flowmetry at each site. Body temperature was controlled with water-perfused suits. Blood pressure was monitored by Finapres, and cutaneous vascular conductance (CVC) calculated (CVC = laser-Doppler flowmetry/mean arterial pressure). The protocol began with a 5- to 10-min baseline period without antagonist perfusion, followed by perfusion of PACAP6-38, l-NAME, or combined PACAP6-38 and l-NAME at the different sites in normothermia (45 min), followed by 3 min of whole body cooling. Whole body heating was then performed to induce heat stress and activate AVD. Finally, 58 mM sodium nitroprusside were perfused at all sites to effect maximal vasodilation for normalization of blood flow data. No significant differences in CVC (normalized to maximum) were found among Ringer's PACAP6-38, l-NAME, or combined antagonist sites during normothermia (P > 0.05 among sites) or cold stress (P > 0.05 among sites). CVC responses at all treated sites were attenuated during AVD (P < 0.05 vs. Ringer's). Attenuation was greater at l-NAME and combined PACAP6-38- and l-NAME-treated sites than at PACAP6-38 sites (P > 0.05). Because responses did not differ between l-NAME and combined treatment sites (P > 0.05), we conclude that VPAC2/PAC1 receptors require NO in series to effect AVD.
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http://dx.doi.org/10.1152/japplphysiol.00859.2012DOI Listing
November 2012

Urease-mediated room-temperature synthesis of nanocrystalline titanium dioxide.

J Am Chem Soc 2012 Aug 20;134(34):13974-7. Epub 2012 Aug 20.

Department of Chemical and Environmental Engineering, University of California, Riverside, California 92521, USA.

Enzymes are an important class of biological molecules whose specific functionalities can be exploited to perform tasks beyond the reach of conventional chemistry. Because they are operational under environmentally friendly, ambient conditions, the adaptation of these biomacromolecules can potentially be used to replace current energy-intensive and environmentally harsh synthesis methods for materials. Here we used a hydrolytic enzyme, urease, to modify the solution environment around a water-soluble and stable TiO(2) precursor to synthesize nanocrystalline titanium dioxide under environmentally benign conditions. This urease-mediated synthesis yields nearly monodisperse TiO(2) nanostructures with high surface area that can be utilized for numerous energy-based applications such as low-cost photovoltaics and photocatalysts.
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http://dx.doi.org/10.1021/ja306884eDOI Listing
August 2012

Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans.

J Appl Physiol (1985) 2011 May 3;110(5):1406-13. Epub 2011 Feb 3.

Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs, South Texas Veterans Health Care System, Audie L. Murphy Memorial Veterans Hospital Division, San Antonio, Texas, USA.

We hypothesized that nitric oxide activation of soluble guanylyl cyclase (sGC) participates in cutaneous vasodilation during whole body heat stress and local skin warming. We examined the effects of the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on reflex skin blood flow responses to whole body heat stress and on nonreflex responses to increased local skin temperature. Blood flow was monitored by laser-Doppler flowmetry, and blood pressure by Finapres to calculate cutaneous vascular conductance (CVC). Intradermal microdialysis was used to treat one site with 1 mM ODQ in 2% DMSO and Ringer, a second site with 2% DMSO in Ringer, and a third site received Ringer. In protocol 1, after a period of normothermia, whole body heat stress was induced. In protocol 2, local heating units warmed local skin temperature from 34 to 41°C to cause local vasodilation. In protocol 1, in normothermia, CVC did not differ among sites [ODQ, 15 ± 3% maximum CVC (CVC(max)); DMSO, 14 ± 3% CVC(max); Ringer, 17 ± 6% CVC(max); P > 0.05]. During heat stress, ODQ attenuated CVC increases (ODQ, 54 ± 4% CVC(max); DMSO, 64 ± 4% CVC(max); Ringer, 63 ± 4% CVC(max); P < 0.05, ODQ vs. DMSO or Ringer). In protocol 2, at 34°C local temperature, CVC did not differ among sites (ODQ, 17 ± 2% CVC(max); DMSO, 18 ± 4% CVC(max); Ringer, 18 ± 3% CVC(max); P > 0.05). ODQ attenuated CVC increases at 41°C local temperature (ODQ, 54 ± 5% CVC(max); DMSO, 86 ± 4% CVC(max); Ringer, 90 ± 2% CVC(max); P < 0.05 ODQ vs. DMSO or Ringer). sGC participates in neurogenic active vasodilation during heat stress and in the local response to direct skin warming.
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http://dx.doi.org/10.1152/japplphysiol.00702.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098662PMC
May 2011

A rapid microtiter plate assay for measuring the effect of compounds on Staphylococcus aureus membrane potential.

J Microbiol Methods 2010 Nov 27;83(2):254-6. Epub 2010 Aug 27.

Antibacterial Discovery Performance Unit, Infectious Diseases Center of Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, Collegeville, PA 19426, United States.

We developed a homogenous microtiter based assay using the cationic dye 3, 3'-Diethyloxacarbocyanine iodide, DiOC2(3), to measure the effect of compounds on membrane potential in Staphylococcus aureus. In a screen of 372 compounds from a synthetic compound collection with anti-Escherichia coli activity due to unknown modes of action at least 17% demonstrated potent membrane activity, enabling rapid discrimination of nuisance compounds.
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http://dx.doi.org/10.1016/j.mimet.2010.08.012DOI Listing
November 2010

Local thermal control of the human cutaneous circulation.

J Appl Physiol (1985) 2010 Oct 3;109(4):1229-38. Epub 2010 Jun 3.

Dept. of Physiology, Univ. of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio TX 78231, USA.

The level of skin blood flow is subject to both reflex thermoregulatory control and influences from the direct effects of warming and cooling the skin. The effects of local changes in temperature are capable of maximally vasoconstricting or vasodilating the skin. They are brought about by a combination of mechanisms involving endothelial, adrenergic, and sensory systems. Local warming initiates a transient vasodilation through an axon reflex, succeeded by a plateau phase due largely to nitric oxide. Both phases are supported by sympathetic transmitters. The plateau phase is followed by the die-away phenomenon, a slow reversal of the vasodilation that is dependent on intact sympathetic vasoconstrictor nerves. The vasoconstriction with local skin cooling is brought about, in part, by a postsynaptic upregulation of α(2c)-adrenoceptors and, in part, by inhibition of the nitric oxide system at at least two points. There is also an early vasodilator response to local cooling, dependent on the rate of cooling. The mechanism for that transient vasodilation is not known, but it is inhibited by intact sympathetic vasoconstrictor nerve function and by intact sensory nerve function.
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http://dx.doi.org/10.1152/japplphysiol.00407.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963328PMC
October 2010

Thermoregulatory and thermal control in the human cutaneous circulation.

Front Biosci (Schol Ed) 2010 Jun 1;2:825-53. Epub 2010 Jun 1.

Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78229, USA.

The past 10-15 years has been a time of focus on the mechanisms of control in the human cutaneous circulation. Methodological developments have provided powerful means for resolving the important contributors to the reflex control of skin blood flow (thermoregulatory control) and also for the equally impressive effects of direct heating and cooling of the skin (thermal control). This review is devoted largely to that recent literature. We treat the sympathetic vasoconstrictor system and its transmitters and modulatory factors and the sympathetic active vasodilator system and its abundant mysteries, with focus on the putative transmitters and cotransmitters, the involvement of nitric oxide and the relationship to sweating and modulatory factors. We also deal with the current understanding of the mechanisms of vasoconstriction and vasodilation that accompany direct skin cooling and heating, noting that adrenergic function, afferent nerve function and the nitric oxide system are involved in the vascular responses to both thermal stimuli.
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http://dx.doi.org/10.2741/s105DOI Listing
June 2010

VIP/PACAP receptor mediation of cutaneous active vasodilation during heat stress in humans.

J Appl Physiol (1985) 2010 Jul 15;109(1):95-100. Epub 2010 Apr 15.

Division of Geriatrics and Gerontology, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA.

Vasoactive intestinal peptide (VIP) is implicated in cutaneous active vasodilation in humans. VIP and the closely related pituitary adenylate cyclase activating peptide (PACAP) act through several receptor types: VIP through VPAC1 and VPAC2 receptors and PACAP through VPAC1, VPAC2, and PAC1 receptors. We examined participation of VPAC2 and/or PAC1 receptors in cutaneous vasodilation during heat stress by testing the effects of their specific blockade with PACAP6-38. PACAP6-38 dissolved in Ringer's was administered by intradermal microdialysis at one forearm site while a control site received Ringer's solution. Skin blood flow was monitored by laser-Doppler flowmetry (LDF). Blood pressure was monitored noninvasively and cutaneous vascular conductance (CVC) calculated. A 5- to 10-min baseline period was followed by approximately 70 min of PACAP6-38 (100 microM) perfusion at one site in normothermia and a 3-min period of body cooling. Whole body heating was then performed to engage cutaneous active vasodilation and was maintained until CVC had plateaued at an elevated level at all sites for 5-10 min. Finally, 58 mM sodium nitroprusside was perfused through both microdialysis sites to effect maximal vasodilation. No CVC differences were found between control and PACAP6-38-treated sites during normothermia (19 +/- 3%max untreated vs. 20 +/- 3%max, PACAP6-38 treated; P > 0.05 between sites) or cold stress (11 +/- 2%max untreated vs. 10 +/- 2%max, PACAP6-38 treated, P > 0.05 between sites). PACAP6-38 attenuated the increase in CVC during whole body heating when compared with untreated sites (59 +/- 3%max untreated vs. 46 +/- 3%max, PACAP6-38 treated, P < 0.05). We conclude that VPAC2 and/or PAC1 receptor activation is involved in cutaneous active vasodilation in humans.
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http://dx.doi.org/10.1152/japplphysiol.01187.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904198PMC
July 2010

Adrenergic control of the human cutaneous circulation.

Appl Physiol Nutr Metab 2009 Oct;34(5):829-39

Department of Physiology, The University of Texas Health Science Center, San Antonio, TX 78229, USA.

The cutaneous circulation is influenced by a variety of thermoregulatory (skin and internal temperature-driven) and nonthermoregulatory (e.g., baroreflex, exercise-associated reflexes) challenges. The responses to these stimuli are brought about through vasoconstrictor nerves, vasodilator nerves, and changes in the local temperature of the vessels themselves. In this review, we examine how thermoregulatory influences mediate changes in skin blood flow through the sympathetic nervous system. We discuss cutaneous vascular responses to both local and whole-body heating and cooling and the mechanisms underlying these responses, with the overarching conclusion that sympathetic function plays significant roles in reflex vasoconstriction and vasodilatation and in the responses to both local cooling and local heating of the skin.
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http://dx.doi.org/10.1139/H09-076DOI Listing
October 2009

Plasma hyperosmolality elevates the internal temperature threshold for active thermoregulatory vasodilation during heat stress in humans.

Am J Physiol Regul Integr Comp Physiol 2009 Dec 7;297(6):R1706-12. Epub 2009 Oct 7.

Department of Environmental Health, Nara Women's University, Kita-Uoya Nishi-Machi, Nara, Japan 630-8506.

Plasma hyperosmolality delays the response in skin blood flow to heat stress by elevating the internal temperature threshold for cutaneous vasodilation. This elevation could be because of a delayed onset of cutaneous active vasodilation and/or to persistent cutaneous active vasoconstriction. Seven healthy men were infused with either hypertonic (3% NaCl) or isotonic (0.9% NaCl) saline and passively heated by immersing their lower legs in 42 degrees C water for 60 min (room temperature, 28 degrees C; relative humidity, 40%). Skin blood flow was monitored via laser-Doppler flowmetry at sites pretreated with bretylium tosylate (BT) to block sympathetic vasoconstriction selectively and at adjacent control sites. Plasma osmolality was increased by approximately 13 mosmol/kgH(2)O following hypertonic saline infusion and was unchanged following isotonic saline infusion. The esophageal temperature (T(es)) threshold for cutaneous vasodilation at untreated sites was significantly elevated in the hyperosmotic state (37.73 +/- 0.11 degrees C) relative to the isosmotic state (36.63 +/- 0.12 degrees C, P < 0.001). A similar elevation of the T(es) threshold for cutaneous vasodilation was observed between osmotic conditions at the BT-treated sites (37.74 +/- 0.18 vs. 36.67 +/- 0.07 degrees C, P < 0.001) as well as sweating. These results suggest that the hyperosmotically induced elevation of the internal temperature threshold for cutaneous vasodilation is due primarily to an elevation in the internal temperature threshold for the onset of active vasodilation, and not to an enhancement of vasoconstrictor activity.
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http://dx.doi.org/10.1152/ajpregu.00242.2009DOI Listing
December 2009

Neuropeptide Y and neurovascular control in skeletal muscle and skin.

Am J Physiol Regul Integr Comp Physiol 2009 Sep 1;297(3):R546-55. Epub 2009 Jul 1.

School of Kinesiology, University of Western Ontario, London, Ontario.

Neuropeptide Y (NPY) is a ubiquitous peptide with multiple effects on energy metabolism, reproduction, neurogenesis, and emotion. In addition, NPY is an important sympathetic neurotransmitter involved in neurovascular regulation. Although early studies suggested that the vasoactive effects of NPY were limited to periods of high stress, there is growing evidence for the involvement of NPY on baseline vasomotor tone and sympathetically evoked vasoconstriction in vivo in both skeletal muscle and the cutaneous circulation. In Sprague-Dawley rat skeletal muscle, Y(1)-receptor activation appears to play an important role in the regulation of basal vascular conductance, and this effect is similar in magnitude to the alpha(1)-receptor contribution. Furthermore, under baseline conditions, agonist and receptor-based mechanisms for Y(1)-receptor-dependent control of vascular conductance in skeletal muscle are greater in male than female rats. In skin, there is Y(1)-receptor-mediated vasoconstriction during whole body, but not local, cooling. As with the NPY system in muscle, this neural effect in skin differs between males and females and in addition, declines with aging. Intriguingly, skin vasodilation to local heating also requires NPY and is currently thought to be acting via a nitric oxide pathway. These studies are establishing further interest in the role of NPY as an important vasoactive agent in muscle and skin, adding to the complexity of neurovascular regulation in these tissues. In this review, we focus on the role of NPY on baseline vasomotor tone in skeletal muscle and skin and how NPY modulates vasomotor tone in response to stress, with the aim of compiling what is currently known, while highlighting some of the more pertinent questions yet to be answered.
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http://dx.doi.org/10.1152/ajpregu.00157.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739783PMC
September 2009

The effect of microdialysis needle trauma on cutaneous vascular responses in humans.

J Appl Physiol (1985) 2009 Apr 5;106(4):1112-8. Epub 2009 Feb 5.

Department of Physiology The University of Texas Health Science Center San Antonio, Texas, USA.

Microdialysis enables in-depth mechanistic study of the cutaneous circulation in humans. However, whether the insertion or presence of the microdialysis fiber (MDF) affects the skin circulation or its responses is unknown. We tested whether the cutaneous vascular response to whole body heating (WBH) was affected by MDF or by pretreatment with ice (part 1) or local anesthesia (LA; part 2). Eleven subjects participated, 9 in part 1 and 8 in part 2 (5 participated in both). In both parts, four sites on the forearm were selected, providing untreated control, MDF only, ice or LA only, and combined MDF plus ice or LA. A tube-lined suit controlled whole body skin temperature, which was raised to approximately 38 degrees C for WBH. Skin sites were instrumented with laser-Doppler flow probes. Data were expressed as cutaneous vascular conductance (CVC). Baseline levels were not different among sites (P > 0.05). In part 1, the internal temperature for the onset of vasodilation was higher (P > 0.05) with MDF with or without ice pretreatment than at untreated control sites (control 36.6 +/- 0.1 degrees C, Ice 36.5 +/- 0.1, MDF 36.8 +/- 0.1 degrees C, and Ice+MDF 36.8 +/- 0.1 degrees C). Peak CVC during WBH was decreased (P < 0.05) by MDF (control 73 +/- 7 vs. MDF 59 +/- 6% of maximal CVC). Ice (73 +/- 6% of maximal CVC) or Ice+MDF (69 +/- 6% of maximal CVC) did not affect (P > 0.05) peak CVC compared with control. In part 2, the temperature threshold for the onset of vasodilation was increased by MDF with or without LA treatment and by LA alone (P < 0.05; control 36.6 +/- 0.1 degrees C, MDF 36.7 +/- 0.1 degrees C, LA 36.8 +/- 0.1 degrees C, and LA+MDF 36.8 +/- 0.1 degrees C). Peak CVC was decreased by MDF (control 69 +/- 6% of maximal CVC vs. MDF 58 +/- 8% of maximal CVC; P < 0.05). LA only (65 +/- 10% of maximal CVC) or MDF in the presence of LA (73 +/- 12% of maximal CVC) did not affect (P > 0.05) peak CVC compared with control. Thus LA or MDF increases the temperature threshold for the onset of vasodilation. MDF alone decreases the peak vasodilator response in CVC to WBH; however, this attenuation did not occur if ice or LA is used before MDF placement. Ice or LA alone do not affect the peak response in CVC to WBH. How those treatments prevent or reverse the effect of MDF placement is presently unclear.
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http://dx.doi.org/10.1152/japplphysiol.91508.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698648PMC
April 2009

The involvement of heating rate and vasoconstrictor nerves in the cutaneous vasodilator response to skin warming.

Am J Physiol Heart Circ Physiol 2009 Jan 14;296(1):H51-6. Epub 2008 Nov 14.

Department of Physiology, The University of Texas Health Science Center, San Antonio, Texas, USA.

Slow local skin heating (LH) causes vasodilator responses, some of which are dependent on sympathetic nerve function. It is not known, however, how the rate of LH affects either the sympathetic or the nonadrenergic components of the responses to LH and whether the adrenergic effects of LH depend on tonic sympathetic activity or whether LH stimulates transmitter release. In part 1, cutaneous vascular conductance (CVC) responses to slow and fast LH (+0.1 degrees and +2 degrees C/min) from 34 degrees to 40 degrees C were compared both at control sites and at sites pretreated with bretylium tosylate (BT; blocks transmitter release from adrenergic terminals). We confirmed, as previously found, the axon reflex (AR) response to slow LH to be blocked by BT (P < 0.05). Pretreatment with BT reduced the AR only with fast LH. BT inhibited the peak vasodilation achieved with both rates of LH (P < 0.05). Longer-term LH was associated with a slow fall in CVC, the classical "die away" phenomenon, at untreated sites (P < 0.05) but not at BT-pretreated sites. Thus the LH-stimulated AR is only partially dependent on intact sympathetic function, and the "die away" phenomenon is dependent on such function. In part 2, we tested whether the conditions in part 1 (whole body and local skin temperatures of 34 degrees C) completely suppressed sympathetic nerve activity. The infusion of BT by microdialysis did not change the CVC (P > 0.05), suggesting the absence of tonic activity in those conditions and therefore that the adrenergic components of the responses in part 1 are via the stimulation of the transmitter release by LH.
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http://dx.doi.org/10.1152/ajpheart.00919.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637777PMC
January 2009

The involvement of norepinephrine, neuropeptide Y, and nitric oxide in the cutaneous vasodilator response to local heating in humans.

J Appl Physiol (1985) 2008 Jul 15;105(1):233-40. Epub 2008 May 15.

Department of Physiology, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.

Presynaptic blockade of cutaneous vasoconstrictor nerves (VCN) abolishes the axon reflex (AR) during slow local heating (SLH) and reduces the vasodilator response. In a two-part study, forearm sites were instrumented with microdialysis fibers, local heaters, and laser-Doppler flow probes. Sites were locally heated from 33 to 40 degrees C over 70 min. In part 1, we tested whether this effect of VCN acted via nitric oxide synthase (NOS). In five subjects, treatments were as follows: 1) untreated; 2) bretylium, preventing neurotransmitter release; 3) N(G)-nitro-L-arginine methyl ester (L-NAME) to inhibit NOS; and 4) combined bretylium + L-NAME. At treated sites, the AR was absent, and there was an attenuation of the ultimate vasodilation (P < 0.05), which was not different among those sites (P > 0.05). In part 2, we tested whether norepinephrine and/or neuropeptide Y is involved in the cutaneous vasodilator response to SLH. In seven subjects, treatments were as follows: 1) untreated; 2) propranolol and yohimbine to antagonize alpha- and beta-receptors; 3) BIBP-3226 to antagonize Y(1) receptors; and 4) combined propranolol + yohimbine + BIBP-3226. Treatment with propranolol + yohimbine or BIBP-3226 significantly increased the temperature at which AR occurred (n = 4) or abolished it (n = 3). The combination treatment consistently eliminated it. Importantly, ultimate vasodilation with SLH at the treated sites was significantly (P < 0.05) less than at the control. These data suggest that norepinephrine and neuropeptide Y are important in the initiation of the AR and for achieving a complete vasodilator response. Since VCN and NOS blockade in combination do not have an inhibition greater than either alone, these data suggest that VCN promote heat-induced vasodilation via a nitric oxide-dependent mechanism.
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http://dx.doi.org/10.1152/japplphysiol.90412.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2494831PMC
July 2008

Exogenous melatonin administration modifies cutaneous vasoconstrictor response to whole body skin cooling in humans.

J Pineal Res 2008 Mar;44(2):141-8

Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.

Humans and other diurnal species experience a fall in internal temperature (T(int)) at night, accompanied by increased melatonin and altered thermoregulatory control of skin blood flow (SkBF). Also, exogenous melatonin induces a fall in T(int), an increase in distal skin temperatures and altered control of the cutaneous active vasodilator system, suggesting an effect of melatonin on the control of SkBF. To test whether exogenous melatonin also affects the more tonically active vasoconstrictor system in glabrous and nonglabrous skin during cooling, healthy males (n = 9) underwent afternoon sessions of whole body skin temperature (T(sk)) cooling (water-perfused suits) after oral melatonin (Mel; 3 mg) or placebo (Cont). Cutaneous vascular conductance (CVC) was calculated from SkBF (laser Doppler flowmetry) and non-invasive blood pressure. Baseline T(int) was lower in Mel than in Cont (P < 0.01). During progressive reduction of T(sk) from 35 degrees C to 32 degrees C, forearm CVC was first significantly reduced at T(sk) of 34.33 +/- 0.01 degrees C (P < 0.05) in Cont. In contrast, CVC in Mel was not significantly reduced until T(sk) reached 33.33 +/- 0.01 degrees C (P < 0.01). The decrease in forearm CVC in Mel was significantly less than in Cont at T(sk) of 32.66 +/- 0.01 degrees C and lower (P < 0.05). In Mel, palmar CVC was significantly higher than in Cont above T(sk) of 33.33 +/- 0.01 degrees C, but not below. Thus exogenous melatonin blunts reflex vasoconstriction in nonglabrous skin and shifts vasoconstrictor system control to lower T(int). It provokes vasodilation in glabrous skin but does not suppress the sensitivity to falling T(sk). These findings suggest that by affecting the vasoconstrictor system, melatonin has a causal role in the nocturnal changes in body temperature and its control.
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http://dx.doi.org/10.1111/j.1600-079X.2007.00501.xDOI Listing
March 2008

The role of baseline in the cutaneous vasoconstrictor responses during combined local and whole body cooling in humans.

Am J Physiol Heart Circ Physiol 2007 Nov 28;293(5):H3187-92. Epub 2007 Sep 28.

Department of Physiology, The University of Texas Health Science Center, San Antonio, TX, USA.

Previous work showed that local cooling (LC) attenuates the vasoconstrictor response to whole body cooling (WBC). We tested the extent to which this attenuation was due to the decreased baseline skin blood flow following LC. In eight subjects, skin blood flow was assessed using laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was expressed as LDF divided by blood pressure. Subjects were dressed in water-perfused suits to control WBC. Four forearm sites were prepared with microdialysis fibers, local heating/cooling probe holders, and laser-Doppler probes. Three sites were locally cooled from 34 to 28 degrees C, reducing CVC to 45.9 +/- 3.9, 42 +/- 3.9, and 44.5 +/- 4.8% of baseline (P < 0.05 vs. baseline; P > 0.05 among sites). At two sites, CVC was restored to precooling baseline levels with sodium nitroprusside (SNP) or isoproterenol (Iso), increasing CVC to 106.4 +/- 12.4 and 98.9 +/- 10.1% of baseline, respectively (P > 0.05 vs. precooling). Whole body skin temperature, apart from the area of blood flow measurement, was reduced from 34 to 31 degrees C. Relative to the original baseline, CVC decreased (P < 0.05) by 44.9 +/- 2.8 (control), 11.3 +/- 2.4 (LC only), 29 +/- 3.7 (SNP), and 45.8 +/- 8.7% (Iso). The reductions at LC only and SNP sites were less than at control or Iso sites (P < 0.05); the responses at those latter sites were not different (P > 0.05), suggesting that the baseline change in CVC with LC is important in the attenuation of reflex vasoconstrictor responses to WBC.
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http://dx.doi.org/10.1152/ajpheart.00815.2007DOI Listing
November 2007

Influence of hyperoxia on skin vasomotor control in normothermic and heat-stressed humans.

J Appl Physiol (1985) 2007 Dec 20;103(6):2026-33. Epub 2007 Sep 20.

Department of Clinical Pathophysiology, School of Health Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.

Hyperoxia induces skin vasoconstriction in humans, but the mechanism is still unclear. In the present study we examined whether the vasoconstrictor response to hyperoxia is through activated adrenergic function (protocol 1) or through inhibitory effects on nitric oxide synthase (NOS) and/or cyclooxygenase (COX) (protocol 2). We also tested whether any such vasoconstrictor effect is altered by body heating. In protocol 1 (n = 11 male subjects), release of norepinephrine from adrenergic terminals in the forearm skin was blocked locally by iontophoresis of bretylium (BT). In protocol 2, the NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) and the nonselective COX antagonist ketorolac (Keto) were separately administered by intradermal microdialysis in 11 male subjects. In the two protocols, subjects breathed 21% (room air) or 100% O(2) in both normothermia and hyperthermia. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure measured by Finapres. In protocol 1, breathing 100% O(2) decreased (P < 0.05) CVC at the BT-treated and at untreated sites from the levels of CVC during 21% O(2) breathing both in normothermia and hyperthermia. In protocol 2, the administration of l-NAME inhibited (P < 0.05) the reduction of CVC during 100% O(2) breathing in both thermal conditions. The administration of Keto inhibited (P < 0.05) the reduction of CVC during 100% O(2) breathing in hyperthermia but not in normothermia. These results suggest that skin vasoconstriction with hyperoxia is partly due to the decreased activity of functional NOS in normothermia and hyperthermia. We found no significant role for adrenergic mechanisms in hyperoxic vasoconstriction. Decreased production of vasodilator prostaglandins may play a role in hyperoxia-induced cutaneous vasoconstriction in heat-stressed humans.
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http://dx.doi.org/10.1152/japplphysiol.00386.2007DOI Listing
December 2007

The cardiovascular challenge of exercising in the heat.

J Physiol 2008 Jan 13;586(1):45-53. Epub 2007 Sep 13.

Centre for Sports Medicine and Human Performance, Brunel University, Uxbridge, Middlesex, UK.

Exercise in the heat can pose a severe challenge to human cardiovascular control, and thus the provision of oxygen to exercising muscles and vital organs, because of enhanced thermoregulatory demand for skin blood flow coupled with dehydration and hyperthermia. Cardiovascular strain, typified by reductions in cardiac output, skin and locomotor muscle blood flow and systemic and muscle oxygen delivery accompanies marked dehydration and hyperthermia during prolonged and intense exercise characteristic of many summer Olympic events. This review focuses on how the cardiovascular system is regulated when exercising in the heat and how restrictions in locomotor skeletal muscle and/or skin perfusion might limit athletic performance in hot environments.
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http://dx.doi.org/10.1113/jphysiol.2007.142158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375553PMC
January 2008

Role of sensory nerves in the cutaneous vasoconstrictor response to local cooling in humans.

Am J Physiol Heart Circ Physiol 2007 Jul 27;293(1):H784-9. Epub 2007 Apr 27.

Department of Physiology-MSC 7756, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.

Local cooling (LC) causes a cutaneous vasoconstriction (VC). In this study, we tested whether there is a mechanism that links LC to VC nerve function via sensory nerves. Six subjects participated. Local skin and body temperatures were controlled with Peltier probe holders and water-perfused suits, respectively. Skin blood flow at four forearm sites was monitored by laser-Doppler flowmetry with the following treatments: untreated control, pretreatment with local anesthesia (LA) blocking sensory nerve function, pretreatment with bretylium tosylate (BT) blocking VC nerve function, and pretreatment with both LA and BT. Local skin temperature was slowly reduced from 34 to 29 degrees C at all four sites. Both sites treated with LA produced an increase in cutaneous vascular conductance (CVC) early in the LC process (64 +/- 55%, LA only; 42 +/- 14% LA plus BT; P < 0.05), which was absent at the control and BT-only sites (5 +/- 8 and 6 +/- 8%, respectively; P > 0.05). As cooling continued, there were significant reductions in CVC at all sites (P < 0.05). At control and LA-only sites, CVC decreased by 39 +/- 4 and 46 +/- 8% of the original baseline values, which were significantly (P < 0.05) more than the reductions in CVC at the sites treated with BT and BT plus LA (-26 +/- 8 and -22 +/- 6%). Because LA affected only the short-term response to LC, either alone or in the presence of BT, we conclude that sensory nerves are involved early in the VC response to LC, but not for either adrenergic or nonadrenergic VC with longer term LC.
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http://dx.doi.org/10.1152/ajpheart.00323.2007DOI Listing
July 2007

Mechanisms of vasoconstriction with direct skin cooling in humans.

Authors:
John M Johnson

Am J Physiol Heart Circ Physiol 2007 Apr 19;292(4):H1690-1. Epub 2007 Jan 19.

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http://dx.doi.org/10.1152/ajpheart.00048.2007DOI Listing
April 2007

How does skin blood flow get so high?

Authors:
John M Johnson

J Physiol 2006 Dec 9;577(Pt 3):768. Epub 2006 Nov 9.

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http://dx.doi.org/10.1113/jphysiol.2006.123406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1890369PMC
December 2006

The involvement of nitric oxide in the cutaneous vasoconstrictor response to local cooling in humans.

J Physiol 2006 Aug 25;574(Pt 3):849-57. Epub 2006 May 25.

Department of Physiology-MSC 7756, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.

Cutaneous vascular conductance (CVC) declines in response to local cooling (LC). Previous work indicates that at least part of the vasoconstrictor response to LC may be through an inhibitory effect on nitric oxide synthase (NOS) activity. In this study we further tested that notion. A total of eight (6 male, 2 female) subjects participated (Part 1 n = 7; Part 2 n = 5, 4 of whom participated in Part 1). Skin blood flow was monitored by laser-Doppler flowmetry. Control of local skin and body temperatures was achieved with Peltier cooler/heater probe holders and water perfused suits, respectively. Microdialysis fibres were inserted aseptically. Saline, L-NAME (20 mM; to inhibit NOS activity) and sodium nitroprusside (SNP 10 microM) were infused by microdialysis. Bretylium tosylate (BT), to block adrenergic function, was administered by iontophoresis. CVC was calculated from blood flow and blood pressure. Part 1 was designed to determine the relative roles of the NO and the adrenergic systems. The infusion of L-NAME elicited a 35 +/- 4% decrease in CVC at the L-NAME and BT + L-NAME sites (P < 0.05); subsequent slow LC (34-24 degrees C) for 35 min caused a significant (P < 0.05) decrease in CVC at control sites (68 +/- 4%) and at the BT treated sites (39 +/- 5%). LC caused a further 23 +/- 5% of initial baseline decrease in CVC at the L-NAME treated sites (P < 0.05). Importantly, CVC at the BT + L-NAME sites was unaffected by LC (P > 0.05). Part 2 was designed to test whether LC influences were specific to the NOS enzymes. Two sites were pretreated with both BT and L-NAME. After 50 min, SNP was added as an NO donor to restore baseline CVC at one site. The same LC process as in Part 1 was applied. There was a 24 +/- 10% decrease (P < 0.05) in CVC at sites with baseline CVC restored, while, as in Part 1, there was no change (P > 0.05) at sites treated with BT + L-NAME only. These data suggest that the vasoconstriction with slow LC is due to a combination of increased noradrenaline release and decreased activity of both NOS per se and of process(es) downstream of NOS.
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http://dx.doi.org/10.1113/jphysiol.2006.109884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1817728PMC
August 2006

Modification of cutaneous vasodilator response to heat stress by daytime exogenous melatonin administration.

Am J Physiol Regul Integr Comp Physiol 2006 Sep;291(3):R619-24

Department of Physiology, University of Texas Health Science Center, San Antonio, Texas, USA.

In humans, the nocturnal fall in internal temperature is associated with increased endogenous melatonin and with a shift in the thermoregulatory control of skin blood flow (SkBF), suggesting a role for melatonin in the control of SkBF. The purpose of this study was to test whether daytime exogenous melatonin would shift control of SkBF to lower internal temperatures during heat stress, as is seen at night. Healthy male subjects (n = 8) underwent body heating with melatonin administration (Mel) or without (control), in random order at least 1 wk apart. SkBF was monitored at sites pretreated with bretylium to block vasoconstrictor nerve function and at untreated sites. Cutaneous vascular conductance, calculated from SkBF and arterial pressure, sweating rate (SR), and heart rate (HR) were monitored. Skin temperature was elevated to 38 degrees C for 35-50 min. Baseline esophageal temperature (Tes) was lower in Mel than in control (P < 0.01). The Tes threshold for cutaneous vasodilation and the slope of cutaneous vascular conductance with respect to Tes were also lower in Mel at both untreated and bretylium-treated sites (P < 0.05). The Tes threshold for the onset of sweating and the Tes for a standard HR were reduced in Mel. The slope of the relationship of HR, but not SR, to Tes was lower in Mel (P < 0.05). These findings suggest that melatonin affects the thermoregulatory control of SkBF during hyperthermia via the cutaneous active vasodilator system. Because control of SR and HR are also modified, a central action of melatonin is suggested.
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http://dx.doi.org/10.1152/ajpregu.00117.2006DOI Listing
September 2006

Relative roles of local and reflex components in cutaneous vasoconstriction during skin cooling in humans.

J Appl Physiol (1985) 2006 Jun 16;100(6):2083-8. Epub 2006 Feb 16.

Department of Physiology-MSC 7756, The University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA.

The reduction in skin blood flow (SkBF) with cold exposure is partly due to the reflex vasoconstrictor response from whole body cooling (WBC) and partly to the direct effects of local cooling (LC). Although these have been examined independently, little is known regarding their roles when acting together, as occurs in environmental cooling. We tested the hypothesis that the vasoconstrictor response to combined LC and WBC would be additive, i.e., would equal the sum of their independent effects. We further hypothesized that LC would attenuate the reflex vasoconstrictor response to WBC. We studied 16 (7 women, 9 men) young (30.5+/-2 yr) healthy volunteers. LC and WBC were accomplished with metal Peltier cooler-heater probe holders and water-perfused suits, respectively. Forearm SkBF was monitored by laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as LDF/blood pressure. Subjects underwent 15 min of LC alone or 15 min of WBC with and without simultaneous LC, either at equal levels (34-31 degrees C) or as equipotent stimuli (34-28 degrees C LC; 34-31 degrees C WBC). The fall in CVC with combined WBC and LC was greater (P<0.05) than for either alone (57.0+/-5% combined vs. 39.2+/-6% WBC; 34.4+/-4% LC) with equipotent cooling, but it was only significantly greater than for LC alone with equal levels of cooling (51.3+/-8% combined vs. 29.5+/-4% LC). The sum of the independent effects of WBC and LC was greater than their combined effects (74.9+/-4 vs. 51.3+/-8% equal and 73.6+/-7 vs. 57.0+/-5% equipotent; P<0.05). The fall in CVC with WBC at LC sites was reduced compared with control sites (17.6+/-2 vs. 42.4+/-8%; P<0.05). Hence, LC contributes importantly to the reduction in SkBF with body cooling, but also suppresses the reflex response, resulting in a nonadditive effect of these two components.
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http://dx.doi.org/10.1152/japplphysiol.01265.2005DOI Listing
June 2006

Human medullary responses to cooling and rewarming the skin: a functional MRI study.

Proc Natl Acad Sci U S A 2006 Jan 9;103(3):809-13. Epub 2006 Jan 9.

Howard Florey Institute of Experimental Physiology and Medicine, Department of Anatomy, University of Melbourne, Melbourne, Victoria 3010, Australia.

A fall in skin temperature precipitates a repertoire of thermoregulatory responses that reduce the likelihood of a decrease in core temperature. Studies in animals suggest that medullary raphé neurons are essential for cold-defense, mediating both the cutaneous vasoconstrictor and thermogenic responses to ambient cooling; however, the involvement of raphé neurons in human thermoregulation has not been investigated. This study used functional MRI with an anatomically guided region of interest (ROI) approach to characterize changes in the blood oxygen level-dependent (BOLD) signal within the human medulla of nine normal subjects during non-noxious cooling and rewarming of the skin by a water-perfused body suit. An ROI covering 4.9 +/- 0.3 mm(2) in the ventral midline of the medulla immediately caudal to the pons (the rostral medullary raphé) showed an increase in BOLD signal of 3.9% (P < 0.01) during periods of skin cooling, compared with other times. Overall, that signal showed a strong inverse correlation (R = 0.48, P < 0.001) with skin temperature. A larger ROI covering the internal medullary cross section at the same level (area, 126 +/- 15 mm(2)) showed no significant change in mean BOLD signal with cooling (+0.2%, P > 0.05). These findings demonstrate that human rostral medullary raphé neurons are selectively activated in response to a thermoregulatory challenge and point to the location of thermoregulatory neurons homologous to those of the raphé pallidus nucleus in rodents.
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http://dx.doi.org/10.1073/pnas.0509862103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1334665PMC
January 2006

Rate dependency and role of nitric oxide in the vascular response to direct cooling in human skin.

J Appl Physiol (1985) 2006 Jan 22;100(1):42-50. Epub 2005 Sep 22.

Department of Physiology, The University of Texas Health Science Center at San Antonio, Texas, USA.

Local cooling of nonglabrous skin without functional sympathetic nerves causes an initial vasodilation followed by vasoconstriction. To further characterize these responses to local cooling, we examined the importance of the rate of local cooling and the effect of nitric oxide synthase (NOS) inhibition in intact skin and in skin with vasoconstrictor function inhibited. Release of norepinephrine was blocked locally (iontophoresis) with bretylium tosylate (BT). Skin blood flow was monitored from the forearm by laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to blood pressure. Local temperature was controlled over 6.3 cm2 around the sites of LDF measurement. Local cooling was applied at -0.33 or -4 degrees C/min. At -4 degrees C/min, CVC increased (P < 0.05) at BT sites in the early phase. At -0.33 degrees C/min, there was no early vasodilator response, but there was a delay in the onset of vasoconstriction relative to intact skin. The NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (intradermal microdialysis) decreased (P < 0.05) CVC by 28.3 +/- 3.8% at untreated sites and by 46.9 +/- 6.3% at BT-treated sites from the value before infusion. Rapid local cooling (-4 degrees C/min) to 24 degrees C decreased (P < 0.05) CVC at both untreated (saline) sites and L-NAME only sites from the precooling levels, but it transiently increased (P < 0.05) CVC at both BT + saline sites and BT + L-NAME sites in the early phase. After 35-45 min of local cooling, CVC decreased at BT + saline sites relative to the precooling levels (P < 0.05), but at BT + L-NAME sites CVC was not reduced below the precooling level (P = 0.29). These findings suggest that the rate of local cooling, but not functional NOS, is an important determinant of the early non-adrenergic vasodilator response to local cooling and that functional NOS, adrenergic nerves, as well as other mechanisms play roles in vasoconstriction during prolonged local cooling of skin.
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http://dx.doi.org/10.1152/japplphysiol.00139.2005DOI Listing
January 2006