The angiotensin II receptor antagonist valsartan inhibits endothelin 1-induced vasoconstriction in the skin microcirculation in humans in vivo: influence of the G-protein beta3 subunit (GNB3) C825T polymorphism

Clinical Pharmacology and Therapeutics
Anna MitchellRené R Wenzel

Abstract

We investigated the influence of angiotensin II receptor blockade on angiotensin II-induced, endothelin 1 (ET-1)-induced, and norepinephrine-induced vasoconstriction to further characterize interactions of the 3 major pressor systems. ET-1, angiotensin II, and norepinephrine act via G protein-coupled receptors with a possible involvement of the G-protein beta3 subunit (GNB3) C825T polymorphism. We studied the influence of this polymorphism on the responses to angiotensin II antagonism in the presence of ET-1, norepinephrine, and angiotensin II. Twenty-five healthy men (mean age, 28.6 +/- 4 years; n = 14 CC, n = 9 CT, and n = 2 TT) were included in a double-blind, randomized, placebo-controlled crossover study. We used a laser Doppler imager to evaluate skin perfusion changes after injection of ET-1, angiotensin II, and norepinephrine (10(-18), 10(-16), and 10(-14) mol) after oral intake of the angiotensin II receptor antagonist valsartan (80 mg) or placebo. Data were analyzed with ANOVA or t test and are expressed as arbitrary perfusion units (PU) (mean +/- SEM). Valsartan abolished angiotensin II-induced vasoconstriction and, more importantly, also ET-1-induced vasoconstriction in the skin microcirculation (ET-1 placebo versus...Continue Reading

Citations

Jan 17, 2009·Journal of Human Hypertension·C SunT Y Wong
May 31, 2011·Pharmacogenomics·Stefanie Klenke, Winfried Siffert
Mar 18, 2008·British Journal of Clinical Pharmacology·Henrik VaseErling B Pedersen
Mar 16, 2007·Clinical Pharmacology and Therapeutics·M SchürksD Rosskopf
Dec 17, 2008·Pharmacological Reviews·Dieter Rosskopf, Martin C Michel
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Dec 1, 2009·Heart Failure Clinics·Richard Sheppard
Jul 17, 2021·Journal of Cardiovascular Pharmacology·Mikael EkholmThomas Kahan

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