The acute administration of either amiloride or captopril does not prevent endothelial dysfunction induced by ischemia and reperfusion in the human forearm vasculature.
Author(s): Luca MC, Liuni A, DiFabio J, Gori T, Parker JD
Affiliation(s): Mount Sinai Hospital, Toronto, ON, Canada.
Publication date & source: 2010-10, Can J Physiol Pharmacol., 88(10):996-1001.
Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't
Animal studies have demonstrated the ability of both sodium-hydrogen exchange inhibitors and angiotensin-converting enzyme inhibitors to reduce infarct size and preserve postischemic ventricular function following ischemia and reperfusion (IR) injury. Whether these interventions can also prevent IR-induced impairment of endothelial function in humans has not been investigated. We performed 2 separate double-blind, placebo-controlled, crossover studies. In the first study, 10 healthy volunteers were randomized to receive oral amiloride (10 mg) or a placebo. In a separate study, another group of volunteers (n = 10) was randomized to receive oral captopril (50 mg) or a placebo. At the time of the peak hemodynamic effect of the drug (3 and 1.5 h after administration of amiloride and captopril, respectively), endothelium-dependent, flow-mediated dilatation of the radial artery was measured before and after IR. IR significantly blunted flow-mediated dilatation in all groups (placebo: pre-IR: 6.8% +/- 0.7%; post-IR: 2.9% +/- 0.9%; P < 0.01; amiloride: pre-IR: 5.9% +/- 0.6%; post-IR: 2.1% +/- 1.3%; P = 0.01; captopril: pre-IR: 6.0% +/- 0.5%; post-IR: 2.0% +/- 0.6%; P < 0.01). In humans, neither 10 mg of oral amiloride nor 50 mg of oral captopril was able to provide protection against IR-induced endothelial dysfunction in the peripheral vasculature.