Systemic Endothelin Receptor Blockade Decreases Peripheral Vascular Resistance and Blood Pressure in Humans

• DOI: 10.1161/01.cir.93.10.1860
• Publication Date: 2012-06-12T00:34:42Z
• Authors: William G. Haynes; Charles J. Ferro; Kevin P. J. O’Kane; David Somerville; Charmaine C. Lomax; David J. Webb
• Keywords: Brachial artery; Endothelin receptor antagonist

Background Although local inhibition of the generation or actions endothelin-1 has been shown to cause forearm vasodilatation, systemic effects endothelin receptor blockade in healthy humans are unknown. We therefore investigated cardiovascular a potent peptide ET A/B antagonist, TAK-044, men. Methods and Results Two randomized, placebo-controlled, crossover studies were performed. In nine subjects, TAK-044 (10 1000 mg IV over 15-minute period) caused sustained dose-dependent peripheral vasodilatation hypotension. Four hours after infusion highest dose (1000 mg), there decreases mean arterial pressure 18 mm Hg total resistance 665 AU increases heart rate 8 bpm cardiac index 0.9 L·min −1 ·m −2 compared with placebo. rapid, increase plasma immunoreactive (from 3.3 35.7 pg/mL within 30 minutes mg). second study eight intravenous administration at doses 30, 250, 750 also all three abolished vasoconstriction brachial artery endothelin-1. Brachial vasodilatation. Conclusions The antagonist vascular and, lesser extent, blood pressure; circulating concentrations; blocks exogenous These results suggest that endogenous plays fundamental physiological role maintenance tone pressure. vasodilator properties antagonists may prove valuable therapeutically.