Enhanced GRK2 expression and desensitization of betaAR vasodilatation in hypertensive patients.

Authors:
Raffaele Izzo
Raffaele Izzo
Hypertension Research Center
Winston-Salem | United States
Ersilia Cipolletta
Ersilia Cipolletta
Department of Clinical Medicine
Italy
Michele Ciccarelli
Michele Ciccarelli
University of Salerno
Fisciano | Italy
Alfonso Campanile
Alfonso Campanile
Ospedale Maggiore Policlinico
Gaetano Santulli
Gaetano Santulli
Federico II University of Naples
Italy
Antonio Vasta
Antonio Vasta
Federico II University of Naples
Italy

Clin Transl Sci 2008 Dec;1(3):215-20

Dipartimento di Medicina Clinica Scienze Cardiovascolari ed Immunologiche, Federico II University of Naples, Italy.

Increased levels of G protein coupled receptor kinase GRK2 appear to participate in hypertension presumably through the desensitization of beta adrenergic receptors (betaARs) that mediate vasodilatation. There are contrasting data on the occurrence of betaAR desensitization in the vasculature, we therefore investigated betaAR vasodilatation and desensitization in normotensives and in hypertensive humans. In blood lymphocytes, we assessed betaAR signaling and GRK2 expression and found betaAR signaling alterations and, consistent with desensitization, ncreased GRK2 levels in hypertensives. We studied in vivo vasodilatation to the betaAR agonist isoproterenol (ISO) injected in the brachia artery in control conditions and during the concomitant infusion of heparin, a known in vitro nonspecific GRK inhibitor. ISO induced a dose-dependent vasorelaxation that was attenuated in hypertensives indicating a loss of betaAR signaling. Intra-arterial infusion of heparin nhibited lymphocyte GRK2 activity and prevented desensitization of betaAR vasodilatation in normotensives. In hypertensives, heparin restored vasodilatation to ISO, to levels observed in normotensives. Our results suggest that betaAR desensitization does indeed occur at the vascular levels in vivo, and that heparin by acting as a GRK inhibitor prevents this in normotensives and restores impaired betaAR vasodilation in hypertensives. We conclude that desensitization participates to impaired betaAR vasodilation in hypertension.

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http://dx.doi.org/10.1111/j.1752-8062.2008.00050.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350663PMC
December 2008
12 Reads
22 Citations
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