3,744 results match your criteria General Pharmacology[Journal]


Endothelium-dependent vasorelaxant and antiproliferative effects of apigenin.

Gen Pharmacol 2000 Dec;35(6):341-7

Department of Pharmacology, The School of Basic Medical Science, Peking University, Beijing 100083, China.

This study was designed to determine whether the relaxant effect of apigenin was endothelium dependent and to examine the possible antiproliferative effect of apigenin. Apigenin relaxed the phenylephrine-precontracted endothelium-intact aortic rings with IC(50) value of 3.7+/-0. Read More

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December 2000
5 Reads

Reversal of hypercapnia induces endothelin-dependent constriction of basilar artery in rabbits with acute metabolic alkalosis.

Gen Pharmacol 2000 Dec;35(6):333-40

Research Service, Veterans Affairs Medical Center, Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, PO Box 670575, Cincinnati, OH 45267-0575, USA.

We recently concluded that constriction of basilar artery due to respiration-induced hypocapnia in rabbits with acute metabolic alkalosis and accompanying compensatory hypercapnia was independent of NO and K(ATP) channels. Based on reports that endothelin-1-mediated hypocapnic constriction of the rabbit basilar artery in vitro, we further investigated whether the respiration-induced hypocapnic constriction was endothelin-1 mediated. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. Read More

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December 2000
4 Reads

Reversal of hypercapnia induces KATP channel and NO-independent constriction of basilar artery in rabbits with acute metabolic alkalosis.

Gen Pharmacol 2000 Dec;35(6):325-32

Research Service, Veterans Affairs Medical Center, Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, PO Box 670575, Cincinnati, OH 45267-0575, USA.

The mechanism of hypocapnic constriction of the cerebral vasculature under conditions of altered acid-base balance has not been investigated. As K(ATP) channels and NO have been implicated in hypocapnic constriction, this study investigated their roles in the constriction due to lowered pCO(2) in hypercapnic rabbits with acute metabolic alkalosis. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. Read More

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December 2000
6 Reads

Contractile responses in spontaneously diabetic mice. II. Effect of cholestyramine on enhanced contractile response of aorta to norepinephrine in C57BL/KsJ (db/db) mice.

Authors:
N Kanie K Kamata

Gen Pharmacol 2000 Dec;35(6):319-23

Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.

To examine the possible role of low-density lipoprotein (LDL) cholesterol in the enhanced norepinephrine (NE)-induced contractile response seen in spontaneously diabetic mice (db/db mice), we examined the effect of chronic administration of cholestyramine on the NE-induced contraction. Although chronic cholestyramine (300 mg/kg, po for 1 month) significantly lowered total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and triglyceride, the plasma glucose and insulin levels were unaffected. The enhanced NE response in diabetic mice was not affected by the chronic administration of cholestyramine. Read More

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December 2000
3 Reads

Contractile responses in spontaneously diabetic mice. I. Involvement of superoxide anion in enhanced contractile response of aorta to norepinephrine in C57BL/KsJ(db/db) mice.

Authors:
N Kanie K Kamata

Gen Pharmacol 2000 Dec;35(6):311-8

Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.

This study investigated the influence of superoxide anion on the norepinephrine (NE)-induced contractile response in spontaneously diabetic mice. In aortic rings with intact endothelium, NE elicited only a slight increase in tension in nondiabetic mice (db/+M), but a much greater dose-dependent contraction in spontaneously diabetic mice (db/db mice). The NE-induced contractile response was significantly reduced by pretreatment with SOD (180 U/ml) in diabetic mice, but not in control mice. Read More

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December 2000
6 Reads

Investigation of basal endothelial function in the obese Zucker rat in vitro.

Gen Pharmacol 2000 Dec;35(6):303-9

School of Pharmacy and Biomedical Sciences, St. Michael's Building, University of Portsmouth, White Swan Road, Portsmouth PO1 2DT, UK.

(a) We studied basal endothelial function in the insulin-resistant, obese Zucker rat, including the influence of superoxide anion on the regulation of contractile reactivity by nitric oxide (NO), following treatment in vivo with the antioxidant tiron or the pro-oxidant combination hydroquinone+buthionine sulfoximine. (b) The leftward shift in the contractile potency of phenylephrine due to NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) was greater in the isolated aorta of the obese Zucker rat relative to its insulin-sensitive littermate, the lean Zucker rat. (c) Pretreatment with tiron depressed vasoconstriction to phenylephrine and comparably enhanced the L-NAME-mediated leftward shift in contractile reactivity in the obese and lean Zucker rats in hydroquinone+buthionine sulfoximine-sensitive manner. Read More

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December 2000
6 Reads

Responses of isolated perfused uterine vascular beds of nonpregnant and pregnant rats to endogenous and exogenous nitric oxide.

Gen Pharmacol 2000 Dec;35(6):297-301

Division of Reproductive Sciences, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX 77555-1062, USA.

The responses to endothelial vasodilators and exogenous nitric oxide (NO) were characterized in intact isolated uterine vascular beds of nonpregnant, midpregnant and late-pregnant rats perfused with Kreb's buffer (37 degrees C, 5% CO(2) in air, pH approximately 7.4) containing 2% dextran and indomethacin. Phenylephrine increased perfusion pressure in the vascular beds equally in all three groups. Read More

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December 2000
4 Reads

Bisphosphonates and atherosclerosis.

Authors:
R Ylitalo

Gen Pharmacol 2000 Dec;35(6):287-96

Department of Pharmacological Sciences, Medical School, University of Tampere, FIN-33014 Tampere, Finland.

Bisphosphonates are used for the treatment of bone resorption, hypercalcemia, osteoporosis and Paget's disease. Etidronate, pamidronate and clodronate also inhibit the development of experimental atherosclerosis without altering serum lipid profile. Bisphosphonates inhibit the arterial calcification, lipid accumulation and fibrosis. Read More

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December 2000
4 Reads

Effects of microenvironmental extracellular pH and extracellular matrix proteins on angiostatin's activity and on intracellular pH.

Authors:
M L Wahl D S Grant

Gen Pharmacol 2000 Nov;35(5):277-85

Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, 233 South, 10th Street, Room 226, Philadelphia, PA 19107, USA.

Antiangiogenic agents target migratory and proliferative endothelial cells (EC) in the process of forming new vessels, resulting in growth inhibition or cell death. Here we have shown that the antiangiogenic activity of angiostatin on EC is enhanced in culture when the microenvironmental extracellular pH (pH(e)) is reduced to levels similar to that of many tumors. In a migration/scratch assay and during tube formation, angiostatin in combination with reduced pH(e) synergistically resulted in an increased EC death--an effect not seen with either stimulus individually. Read More

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November 2000
4 Reads

The role of peroxisome proliferator-activated receptor gamma in bladder cancer in relation to angiogenesis and progression.

Gen Pharmacol 2000 Nov;35(5):269-75

Institute of Biomedical Sciences, University of Ancona, Montedago, I 60131 Ancona, Italy.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) immunohistochemical expression was analyzed in 75 human bladder tumor specimens, where the expression of some angiogenic factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PDECGF), and tumor progression markers, such as epidermal growth factor receptor (EGFr), p16, mutated p53, and normal pRB, were also analyzed. The results were then compared to the clinical and pathological characteristics of the disease. PPAR gamma was expressed more significantly in papillary tumors than in solid cancers, and its presence was associated with statistical significance to low incidence of tumor recurrence or progression. Read More

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November 2000
3 Reads

Locating the active site for angiogenesis and cell proliferation due to fibrin fragment E with a phage epitope display library.

Gen Pharmacol 2000 Nov;35(5):261-7

Department of Pathology, University of Aberdeen Medical School, Aberdeen Royal Infirmary, Aberdeen AB25 2ZD, UK.

The plasmin-mediated lysis of fibrin present in a wound, or in chronic inflammatory disease, results in the release of fibrin degradation products. One of the two major products is fibrin fragment E, which has been shown to stimulate cell proliferation in many cell types including endothelium, fibroblasts, and smooth muscle cells, and to be angiogenic in the chick chorioallantoic membrane (CAM) system. The activity of fibrin fragment E is dependent on N-terminus thrombin action. Read More

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November 2000
3 Reads

Thrombin regulates the expression of proangiogenic cytokines via proteolytic activation of protease-activated receptor-1.

Gen Pharmacol 2000 Nov;35(5):255-9

Institute of General Physiology, University of Siena, Via Aldo Moro, 53100 Siena, Italy.

In addition to its central role in blood coagulation and hemostasis, human alpha-thrombin is a growth factor for a variety of cell types, including monocytes and endothelial cells, involved in the control of angiogenesis. Different cytokines produced by mononuclear cells have been implicated in angiogenic processes associated with tissue repair and certain human malignancies. We have previously shown that thrombin enhances proliferative responses in T lymphocytes. Read More

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November 2000
3 Reads

Thrombin peptide, TP508, stimulates angiogenic responses in animal models of dermal wound healing, in chick chorioallantoic membranes, and in cultured human aortic and microvascular endothelial cells.

Gen Pharmacol 2000 Nov;35(5):249-54

Chrysalis BioTechnology, Inc., 2200 Market Street, Suite 600, Galveston, TX 77550, USA.

The alpha-thrombin peptide, TP508, accelerates the healing of full-thickness wounds in both normal and ischemic skin. In wounds treated with TP508, a pattern of increased vascularization is consistently observed both grossly and microscopically when compared to wounds treated with saline. One possible mechanism by which the peptide accelerates wound healing is by promoting revascularization of granulation tissue at the injured site. Read More

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November 2000
3 Reads

Effects of thrombin and of the phospholipase C inhibitor, D609, on the vascularity of the chick chorioallantoic membrane.

Gen Pharmacol 2000 Nov;35(5):241-7

Department of Anatomy, University of Mainz, D-55099 Mainz, Germany.

Microvascular corrosion casting was used to assess the effects of thrombin and D609, a phospholipase C inhibitor, on the vascularity of the chick embryo chorioallantoic membrane (CAM). Discs containing vehicle, thrombin or D609 were placed on the CAM of fertilized white Leghorn eggs on Day 9 of gestation and vascularity was assessed on Day 11. Thrombin caused significant increases in the numbers (43%), diameters (5%) and lengths (17%), of both pre- and postcapillaries (first-order vessels by centripetal ordering). Read More

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November 2000
4 Reads

Experimental models of growth factor-mediated angiogenesis and blood-retinal barrier breakdown.

Gen Pharmacol 2000 Nov;35(5):233-9

Wilmer Eye Institute, Johns Hopkins University School of Medicine, 825 Maumenee Building, 600 North Wolfe Street, 21287-9289, Baltimore, MD 21287-9289, USA.

Following chronic ischemia, vascular endothelial growth factor (VEGF) is induced primarily in the ganglion cell layer of the retina. This often results in neovascularization (NV) that originates from the vascular bed closest to the ganglion cell layer. To study the effects of VEGF, independent lines of transgenic mice that express VEGF in the lens and in the retina have been generated. Read More

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November 2000
2 Reads

The discovery of angiogenic factors: a historical review.

Gen Pharmacol 2000 Nov;35(5):227-31

Department of Human Anatomy and Histology, University of Bari Medical School, Piazza G. Cesare, 11, Policlinico, 70124 Bari, Italy.

Angiogenesis is a biological process by which new capillaries are formed and it occurs in many physiological and pathological conditions. It is controlled by the net balance between molecules that have positive and negative regulatory activity and this concept had led to the notion of the "angiogenic switch," depending on an increased production of one or more of the positive regulators of angiogenesis. Numerous inducers of angiogenesis have been identified and this review offers a historical account of the relevant literature concerning the discovery of the best-characterized angiogenic factors. Read More

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November 2000
3 Reads

Angiogenesis in health and disease.

Authors:
M E Maragoudakis

Gen Pharmacol 2000 Nov;35(5):225-6

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November 2000
2 Reads

Influences of nonselective, beta(1)-selective and vasodilatory beta(1)-selective beta-blockers on arterial pulse wave velocity in normotensive subjects.

Gen Pharmacol 2000 Oct;35(4):219-24

Department of Clinical Physiology, University of Tampere, FIN-33014, Tampere, Finland.

beta-Adrenoceptor blockers with disparate properties may have differential influences on arterial pulse wave velocity (PWV). Therefore, influences of single medium doses of bisoprolol, propranolol and celiprolol on PWV were compared in healthy subjects. Arterial PWV was obtained from the time delay between flow pulses measured from the root of the aorta and the popliteal artery. Read More

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October 2000
3 Reads

Quantification of pulmonary capillary endothelium-bound angiotensin converting enzyme inhibition in man.

Gen Pharmacol 2000 Oct;35(4):213-8

Vascular Biology Center, Medical College of Georgia, Augusta, 30912-2500, USA.

Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal ectoenzyme expressed abundantly on the pulmonary capillary endothelium and recognized as the site for the conversion of circulating angiotensin I to II. In the present study, we have applied recently developed methodologies for assaying pulmonary capillary endothelium-bound (PCEB) ACE activity in man, to estimate the interaction of an ACE inhibitor (enalaprilat) with PCEB ACE in human subjects. Trace amounts of the specific ACE substrate, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP; 40 Ci or 2 nmol), was injected as a bolus into the subclavian vein and immediately blood was withdrawn from a radial arterial catheter. Read More

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October 2000
4 Reads

Pentoxifylline potentiates nitric oxide production in interleukin-1beta-stimulated vascular smooth muscle cells through cyclic AMP-dependent protein kinase A pathway.

Gen Pharmacol 2000 Oct;35(4):205-11

Department of Microbiology and Immunology, School of Medicine, Wonkwang University, Iksan, 570-749, Chonbuk, South Korea.

In the present study, we observed that pentoxifylline (PTX) significantly augmented the nitric oxide (NO) production and the iNOS gene expression by interleukin-1beta (IL-1beta)-stimulated vascular smooth muscle cells (VSMCs). The enhancing effects of PTX on the IL-1beta-induced NO production was associated with an increased intracellular cyclic AMP (cAMP) levels, and the synergistic effects of PTX on the IL-1beta-induced NO production was blocked by cAMP-dependent protein kinase A (PKA) inhibitors. PKA inhibitors, KT5720 and H89, markedly decreased the augmented expression of iNOS gene whereas ODQ, a soluble guanylate cyclase inhibitor, did not affect the enhancing effect. Read More

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October 2000
5 Reads

Enhancement of hydralazine hypotension by low doses of isoniazid. Possible role of semicarbazide-sensitive amine oxidase inhibition.

Gen Pharmacol 2000 Oct;35(4):195-204

Department of Pharmacology, School of Medicine, Universidad Nacional Autonoma de Mexico, Apartado Postal 70-297, 04510, D.F., Mexico, Mexico.

The influence of pretreatment with 1 through 300 mg/kg ip of isoniazid (ISO) on blood pressure and heart rate responses to 0.1 mg/kg iv of hydralazine (HYD) was assessed in rats anesthetized with chloralose--urethane. HYD hypotension was significantly enhanced by ISO at doses between 3 and 300 mg/kg ip. Read More

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October 2000
2 Reads

Protective effect of allopurinol in the renal ischemia--reperfusion in uninephrectomized rats.

Gen Pharmacol 2000 Oct;35(4):189-93

Department of Urology, Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre (FFFCMPA), Rua Jaragua, 370/302, Bairro Bela Vista, RS 90450-140, Porto Alegre, Brazil.

The effect of allopurinol (an inhibitor of xanthine oxidase) on oxidative stress, renal dysfunction, and histologic alterations was evaluated during the renal ischemia--reperfusion in uninephrectomized rats. Renal malondialdehyde and serum creatinine levels significantly increased after renal ischemia--reperfusion. However, the pretreatment with allopurinol demonstrated a protector effect in these parameters. Read More

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October 2000
2 Reads

Antithrombotic and thrombolytic activities of Agkisacutacin, a snake venom proteinase, in experimental models.

Gen Pharmacol 2000 Oct;35(4):179-87

Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, 230022, Hefei, China.

The antithrombotic and thrombolytic activities of Agkisacutacin (Agk), a component isolated from Agkistrodon acutus, were determined in vitro and in vivo. The models employed included Chandler's model, arterio-venous shunt model and pulmonary embolus model. The effects of Agkisacutacin on coagulation, plasma fibrinogen and platelet aggregation induced by collagen, adenosine diphosphate (ADP) and thrombin were also investigated. Read More

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October 2000
3 Reads

Adenosine A(2A) and A(2B) receptors mediated nitric oxide production in coronary artery endothelial cells.

Gen Pharmacol 2000 Sep;35(3):171-7

Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.

The present study further examined the functional presence and the signal transduction mechanism(s) for adenosine A(2A) and A(2B) receptors through nitric oxide (NO) and the guanosine 3', 5'-cyclic monophosphate (cGMP) pathway in cultured porcine coronary artery endothelial cells (PCAEC). The application of adenosine receptor agonists, NECA, CGS-21680 and CAD between 10(-7) and 10(-4) M, enhanced the production of NO (measured as nitrite) in a dose-dependent manner. On the basis of EC(50) values, these agonists showed the following order of potency: NECA>CGS-21680>CAD. Read More

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September 2000
4 Reads

Role of heat shock protein 90 in bradykinin-stimulated endothelial nitric oxide release.

Gen Pharmacol 2000 Sep;35(3):165-70

Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912-2500, USA.

Previously we described ENAP-1, a 90-kDa protein that is tyrosine-phosphorylated in endothelial cells in response to bradykinin (BK) stimulation and is associated with endothelial nitric oxide synthase (eNOS). Subsequently, other investigators demonstrated that eNOS interacts with heat shock protein 90 (Hsp90) following stimulation of endothelial cells with vascular endothelial growth factor (VEGF), histamine, or fluid shear stress. Therefore, we tested the hypotheses that ENAP-1 and Hsp90 are the same protein and that BK activation of eNOS is dependent on Hsp90. Read More

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September 2000
2 Reads

Role of nitric oxide in maintenance of basal oral tissue blood flow in anesthetized cats.

Authors:
M C Koss Y Yu

Gen Pharmacol 2000 Sep;35(3):159-64

Department of Cell Biology, University of Oklahoma, College of Medicine, 940 Stanton L. Young Street, Biomed. Res. Sci. Building 724, Oklahoma City, OK 73190, USA.

Experiments were undertaken to determine if nitric oxide (NO) plays a role in regulation of basal blood flow in the oral cavity of pentobarbital anesthetized cats and, if so, to quantify this effect using dose-response relationships. Blood flow was continuously measured from the surface of the tongue and mandibular gingiva (laser-Doppler flowmetry) and from the lingual artery (ultrasonic flowmetry). Cardiovascular parameters also were recorded. Read More

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September 2000
2 Reads

Investigation of vascular endothelial growth factor effects on pulmonary endothelial monolayer permeability and neutrophil transmigration.

Gen Pharmacol 2000 Sep;35(3):149-57

Department of Pharmacology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.

This study sought to determine whether vascular endothelial growth factor (VEGF)-induced permeabilisation of pulmonary endothelium to macromolecules could be related to a permissive role for neutrophil-derived VEGF in neutrophil transmigration. Treatment of human pulmonary artery endothelial cell (HPAEC) monolayers with 1, 10 or 100 ng/ml VEGF for 15 min or 1, 10 ng/ml for 90 min significantly increased endothelial permeability to trypan blue-labelled albumin (TB-BSA). These increases were correlated with changes in the cellular distribution of F-actin, as visualised by rhodamine-phalloidin staining: increased stress fibre formation, cellular elongation and formation of intercellular gaps after 15 min; at 90 min, there was also evidence of microspike formation and extension of spindle processes from the cell surface. Read More

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September 2000
3 Reads

Intravenous BQ-123 and phosphoramidon reduce ventricular ectopic beats and myocardial infarct size in dogs submitted to coronary occlusion and reperfusion.

Gen Pharmacol 2000 Sep;35(3):143-7

Departamento de Fisiología, Facultad de Medicina, Universidad de Valencia, Av. Blasco Ibáñez, 17, 46010 Valencia, Spain.

The aim of this work was to investigate the influence of endothelin on myocardial ischemia and reperfusion in anaesthetized dogs. Animals were submitted to left thoracotomy and 120 min of left anterior descending coronary occlusion, followed by 180 min of reperfusion. Arterial blood pressure and electrocardiogram (ECG) were recorded in order to analyze heart rate (HR)-pressure product and production of ectopic beats. Read More

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September 2000
4 Reads

Effect of Korea red ginseng on the blood pressure in conscious hypertensive rats.

Gen Pharmacol 2000 Sep;35(3):135-41

Department of Physiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Taejon 301-131, South Korea. ac.kr

The change of blood pressure and heart rate after intravenous injection of Korea red ginseng (KRG) were studied in the conscious normotensive and one-kidney, one-clip Goldblatt hypertensive (1K, 1C-GBH) rats. Crude saponin (CS) of KRG (50, 100 mg/kg i.v. Read More

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September 2000
2 Reads

Contribution of endothelium-derived relaxing factors to P2Y-purinoceptor-induced vasodilation in the isolated rat kidney.

Gen Pharmacol 2000 Sep;35(3):129-33

Departamento de Fisiología, Facultad de Medicina, Unidad de Nefrología Experimental, Hospital Virgen de las Nieves, E-18012 Granada, Spain.

We examined the role of endothelium-derived relaxing factors nitric oxide (NO), endothelium-derived hyperpolarising factor (EDHF), and prostaglandins (PGs) to P(2Y1)- and P(2Y2)-purinoceptor-induced vasodilation in isolated rat kidney. To do it, we analysed the renal response to ATP, 2-methylthio ATP, and UTP in rat renal vasculature under normal conditions and after the administration of: N(w)-nitro-L-arginine (L-NAME), increased K(+) concentration, indomethacin, and L-NAME and increased K(+) together. Our results indicate that the vasodilator response to P(2Y1)- and P(2Y2)-purinoceptor activation in the isolated perfused kidney of rats is subserved by EDHF and NO. Read More

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September 2000
3 Reads

Functional heterogeneity of large and small resistance arteries isolated from biopsies of subcutaneous fat: implications for investigation of vascular pathophysiology.

Gen Pharmacol 2000 Sep;35(3):119-27

Department of Medical Sciences, Western General Hospital, Hugh Robson Building, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, Scotland, UK.

Few studies using human subcutaneous resistance arteries acknowledge the possibility of functional heterogeneity in these vessels. Large ( approximately 500 microm) and small (> or = 200 microm) resistance arteries (n=11) and veins (n=5) were identified using physical, structural and functional criteria in 14 biopsies of human gluteal fat. Endothelium-dependent relaxation was not evident in veins, while, unlike small resistance arteries (E(max) 95. Read More

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September 2000
3 Reads

Maturation attenuates the effects of cGMP on contraction, [Ca2+]i and Ca2+ sensitivity in ovine basilar arteries.

Gen Pharmacol 2000 Aug;35(2):107-18

Center for Perinatal Biology, Department of Physiology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.

The present study explores the hypothesis that age-related variations in cerebrovascular responses to vasodilators reflect corresponding age-dependent differences in the mechanisms coupling changes in cytosolic cGMP to vasorelaxation. The experiments focused on cGMP's ability to decrease either [Ca2+]i or myofilament Ca2+ sensitivity, because both effects can contribute to cGMP-induced vasodilation. Use of the cGMP analog 8-pCPT-cGMP minimized problems associated with limited cell permeation or cGMP hydrolysis. Read More

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August 2000
4 Reads

Cardiovascular effects of ketanserin on normotensive rats in vivo and in vitro.

Gen Pharmacol 2000 Aug;35(2):95-105

Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782, Santiago de Compostela, Spain.

In this work, we report for first time that: (1) low doses of ketanserin (0.2 mg/kg) produce a transient hypotensive response in anaesthetized rats, which is basically due to the blockade of 5-hydroxytryptamine (2A) (5-HT)2A receptors, whereas high doses (1 mg/kg) of ketanserin cause a sustained hypotension also mediated by the blockage of alpha1-adrenergic receptors; (2) the in vitro vasorelaxant action of high concentrations of ketanserin (>10 microM) involves Ca2+ antagonism, which may also be responsible, at least in part, for the inhibition of high-K+-induced 45Ca2+ uptake, the inhibition of Ca2+-induced contractions in initially Ca2+-free high-K+ medium, and the negative chronotropic effects on isolated atria. This Ca2+ antagonistic activity does not seem to contribute to the in vivo cardiovascular effects of ketanserin at therapeutic doses. Read More

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August 2000
2 Reads

Interaction between thromboxane A2 and 5-hydroxytryptamine in the radial artery compared to the internal thoracic artery.

Gen Pharmacol 2000 Aug;35(2):89-93

Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College of Science Technology and Medicine, Heart Science Centre, Harefield Hospital, Middlesex UB9 6JH, Harefield, UK.

The aim of the present study was to investigate if the function of 5-hydroxytryptamine-1B/1D (5-HT1B/1D) receptors in human radial artery (RA) and internal thoracic artery (ITA) can be modified by thromboxane A2 (TXA2) released from the vessel wall in these two arteries that are commonly used in coronary artery bypass grafts. The 5-HT1B/1D agonist sumatriptan contracted the RA with a maximum response of 23.5+/-6. Read More

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August 2000
2 Reads

An association of anti-elastin IgA antibodies with development of retinopathy in diabetic children.

Gen Pharmacol 2000 Aug;35(2):83-7

Department of Biology and Pathological Physiology, University School of Medicine, 1 St. Kliment Ohridski Street, 5800, Pleven, Bulgaria.

An important factor in the development of vascular wall alterations is degradation of the elastic fiber major protein-elastin. Elastin peptides derived from this degradation are present in the circulating blood and they are a stimulus for increased production of anti-elastin antibodies (AEAb). The aim of the present study was to examine the possible association between serum elastin AEAb and the development of diabetic vascular complications. Read More

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August 2000
2 Reads

Effect of N-acetylcysteine on colitis induced by acetic acid in rats.

Gen Pharmacol 2000 Aug;35(2):77-81

Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dúbravská cesta 9, 842 16, Bratislava, Slovak Republic.

(1) To verify the proposed role of reactive oxygen species (ROS) in ulcerative colitis, the effect of an antioxidant N-acetylcysteine (NAC) was studied in acetic acid (AA)-induced colonic inflammation. (2) Depending on the dose used, NAC administered intracolonically was found to reduce the extent of colonic damage, along with a decrease in myeloperoxidase (MPO) activity, colonic wet weight and wet/dry weight ratio. (3) NAC attenuated the enhanced vascular permeability and prevented the depletion of colonic reduced glutathione (GSH) caused by AA administration. Read More

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August 2000
2 Reads

YM905, a novel M3 antagonist, inhibits Ca2+ signaling and c-fos gene expression mediated via muscarinic receptors in human T cells.

Authors:
T Fujii K Kawashima

Gen Pharmacol 2000 Aug;35(2):71-5

Department of Pharmacology, Kyoritsu College of Pharmacy, 1-5-30 Shibakoen, Minato-ku, 105-8512, Tokyo, Japan.

Our earlier observations suggest that M3 muscarinic acetylcholine (ACh) receptors (mAChRs) are involved in Ca2+ signaling and regulation of c-fos gene expression in T lymphocytes. Here, we describe the effects of YM905, a novel M3 antagonist, on evoked Ca2+ signaling and c-fos gene expression in CEM human leukemic T cells. YM905 significantly inhibited increases in intracellular free Ca2+ evoked by 10 microM oxotremorine-M, an M1/M3 agonist (IC50=100 nM), and also inhibited 10 microM oxotremorine-M-induced upregulation of c-fos gene expression at 1 microM. Read More

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August 2000
3 Reads

The effects of propofol on normal and hypercholesterolemic isolated rabbit heart.

Gen Pharmacol 2000 Aug;35(2):65-70

Department of Anesthesiology and Reanimation, School of Medicine, Dokuz Eylul University, Balcova 35340, Izmir, Turkey.

The aim of the present study was to compare the effects of propofol on cardiac contractile force in normal and hypercholesterolemic isolated rabbit hearts. While one group was fed with standard chow pellets (150 g/day), the other group received cholesterol (1% w/w) in addition to the same amount of rabbit chow pellets during 1 month. Hearts from standard-fed rabbits were given intralipid solvent or 25, 50 and 100 microM propofol by infusion. Read More

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August 2000
2 Reads

Relationship between elastin-derived peptides and the development of microvascular complications: a longitudinal study in children with Type 1 (insulin-dependent) diabetes mellitus.

Gen Pharmacol 2000 Aug;35(2):59-64

Department of Biology and Immunology, University School of Medicine, St. Kliment Ohridski Street No. 1, 5800, Pleven, Bulgaria.

Levels of elastin-derived peptides (EDP) were determined by enzyme-linked immunosorbent assay (ELISA) in sera of 28 children with Type 1 (insulin-dependent) diabetes mellitus (mean age 11.6+/-2.8 years, diabetes duration 5. Read More

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August 2000
3 Reads

A unique xanthine derivative KMCP-98 with activation of adenosine receptor subtypes.

Gen Pharmacol 2000 Jul;35(1):47-57

Department of Pharmacology, College of Medicine, Kaohsiung Medical University, 100 Shin-Chuan 1st Road, Kaohsiung 807, Taiwan.

KMCP-98 is a newly synthesized adenosine receptor agonist by alkylation at the 7-position of the xanthines nucleus. We first investigated the pharmacological activities of KMCP-98 under in vivo and in vitro conditions. Acute intravenous injection of KMCP-98 (1. Read More

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July 2000
2 Reads

Effect of nitric oxide on calcium-induced calcium release in coronary arterial smooth muscle.

Gen Pharmacol 2000 Jul;35(1):37-45

Department of Pharmacology and Toxicology, Medical College of Wisconsin, 53226, Milwaukee, WI, USA

The present study was designed to determine whether nitric oxide (NO)-induced reduction of [Ca(2+)](i) is associated with Ca(2+)-induced Ca(2+) release (CICR) in coronary arterial smooth muscle cells (CASMCs). Caffeine was used as a CICR activator to induce Ca(2+) release in these cells. The effects of NO donor, sodium nitroprusside (SNP), on caffeine-induced Ca(2+) release were examined in freshly dissociated bovine CASMCs using single cell fluorescence microscopic spectrometry. Read More

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July 2000
2 Reads

Characterization of adenosine action in isolated rat renal artery. Possible role of adenosine A(2A) receptors.

Gen Pharmacol 2000 Jul;35(1):29-36

Department of Clinical Pharmacology, Pharmacology and Toxicology, Medical Faculty, University of Belgrade, P.O. Box 840, 11000 Belgrade, Yugoslavia.

Adenosine (0.1-300 microM) induced concentration- and endothelium-dependent relaxation of rat renal artery (RRA). N(G)-Nitro-L-arginine (L-NOARG, 10 microM) significantly reduced adenosine-elicited dilatation, but not the application of indomethacin (10 microM), ouabain (100 microM) or tetraethylammonium (TEA, 500 microM). Read More

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July 2000
2 Reads

Inhibitory effect of ethyl acetate fraction from Cudrania tricuspidata on the expression of nitric oxide synthase gene in RAW 264.7 macrophages stimulated with interferon-gamma and lipopolysaccharide.

Gen Pharmacol 2000 Jul;35(1):21-8

Department of Microbiology and Immunology, Wonkwang University School of Medicine, 344-2, Shinyong-dong, Iksan-shi, Chonbuk 570-749, South Korea.

It was found that the production of nitric oxide (NO) by RAW 264.7 macrophages stimulated with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) could be markedly inhibited by the ethyl-acetate-soluble fraction of 80% aqueous methanolic extract of stem barks of Cudrania tricuspidata (EACT). Inhibition of NO production was achieved by reducing inducible nitric oxide synthase (iNOS) expression at protein and mRNA levels and by inactivating nuclear factor-kappa B (NF-kappa B), but not by inhibiting iNOS activity. Read More

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July 2000
2 Reads

The antioxidant effect of free bilirubin on cumene-hydroperoxide treated human leukocytes.

Gen Pharmacol 2000 Jul;35(1):17-20

Department of Biochemistry, School of Medicine, Akdeniz University, 07070 Antalya, Turkey.

To examine the antioxidant effect of bilirubin (BR) on leukocyte, we treated leukocytes obtained from healthy subjects with an oxidant and various concentrations of BR. High concentrations of BR decreased thiobarbituric acid reactive substances (TBARS) and catalase activities, increased superoxide dismutase (SOD) activity, but had no effect on glutathione (GSH) concentration. Our results showed that under physiological conditions, BR has an antioxidant effect only in high concentrations. Read More

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July 2000
21 Reads

Reduced verapamil inhibition of endothelin-1-constricted rabbit basilar artery due to enhanced non L-type Ca(2+)-channel-dependent constriction.

Gen Pharmacol 2000 Jul;35(1):11-5

Surgical Service, Veterans Affairs Medical Center, Department of Neurosurgery, University of Cincinnati College of Medicine, PO Box 670515, Cincinnati, OH 45267-0515, USA.

This study tested whether (1) L-type Ca(2+) channel blockade and extracellular Ca(2+) removal prior to endothelin-1, as compared to during the endothelin-1 constriction, resulted in lesser inhibition, and (2) the reduced inhibition due to prior L-type Ca(2+) channel blockade resulted from enhanced non L-type Ca(2+)-channel-dependent constriction. Pretreatment of rabbit basilar artery in vitro with 1 microM verapamil, an L-type Ca(2+) channel blocker, inhibited 3, 10, 30, and 100 nM endothelin-1 constrictions to a lesser extent than verapamil addition during the plateau endothelin-1 constriction. Ni(2+) (0. Read More

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July 2000
3 Reads

17 beta-estradiol protects lymphocytes against dopamine and iron-induced apoptosis by a genomic-independent mechanism. Implication in Parkinson's disease.

Gen Pharmacol 2000 Jul;35(1):1-9

School of Medicine, University of Antioquia, Calle 62 #52-72, P.O. Box 1226, Medellin, Colombia.

Dopamine (DA) in combination with iron (Fe(2+)) has been demonstrated to induce apoptosis in neuronal-like PC12 cells by an oxidative stress mechanism. To get a better insight of cell death and protective mechanisms in DA/Fe(2+)-induced toxicity, we investigated the effects of DA/Fe(2+) and the antioxidant action of 17 beta-estradiol (E2) in peripheral blood lymphocytes (PBL). We found that DA/Fe(2+)-induces apoptosis in PBL via a hydrogen peroxide (H(2)O(2))-mediated oxidative mechanism, which in turn triggers a cascade of molecular events requiring RNA and de novo protein synthesis. Read More

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July 2000
3 Reads

Relaxation induced by histamine is not endothelium dependent in tail arteries of L-NAME-treated rats.

Gen Pharmacol 2000 Jun;34(6):435-41

Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/no., SP-14040-903, Ribeirão Preto, Brazil.

The present study was carried out to evaluate the relaxation induced by histamine in tail arteries of rats after chronic inhibition of nitric oxide (NO) synthesis with the inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) compared to tail arteries of control rats. The maximum relaxation induced by histamine was greater in control (88.09% +/-5. Read More

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June 2000
2 Reads

Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae.

Gen Pharmacol 2000 Jun;34(6):429-34

Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi, Tokyo 193-0392, Hachioji, Japan.

Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T(4)) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscarinic receptor-mediated vascular responses alter at an early stage of the disease. T(4) treatment was sufficient to induce a significant degree of thyroid weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T(4) levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidism. Read More

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June 2000
4 Reads

Spiradoline, a kappa opioid receptor agonist, produces tonic- and use-dependent block of sodium channels expressed in Xenopus oocytes.

Gen Pharmacol 2000 Jun;34(6):417-27

Department of Microbiology and Molecular Genetics, University of California, 92697-4025, Irvine, CA, USA.

Spiradoline, an arylacetamide kappa (kappa) opioid receptor agonist, produced a potent tonic block of rat neuronal (EC(50)= 34+/-5 microM) and heart (EC(50)= 183+/-13 microM) sodium channels and also blocked IFMQ3 mutant neuronal sodium channels (EC(50)= 130+/-34 microM) that lack fast inactivation when expressed in Xenopus oocytes. Spiradoline produced a hyperpolarizing shift in the voltage-dependence of sodium channel inactivation and exhibited a marked frequency-dependent component to blockade of sodium channels. The onset of open channel block of the IFMQ3 channel by spiradoline was best fit with a first-order blocking scheme, yielding an affinity constant of 116 +/- 33 microM. Read More

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June 2000
2 Reads

Postglomerular vasoconstriction to angiotensin II and norepinephrine depends on intracellular calcium release.

Gen Pharmacol 2000 Jun;34(6):409-15

Department of Physiology, Tulane University School of Medicine, SL39, 1430 Tulane Avenue, 70112, New Orleans, LA, USA.

The current study was performed to determine the effect of calcium store depletion with cyclopiazonic acid (CPA) on the pre- and postglomerular vasoconstrictor responses to angiotensin II (ANG II) and norepinephrine (NE). CPA treatment significantly attenuated the afferent arteriolar response to 10 nM ANG II by 51% and to 1000 nM NE by 19%. Efferent arteriolar responses to ANG II and NE were also greatly attenuated in the presence of CPA. Read More

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June 2000
3 Reads