The acute administration of either amiloride or captopril does not prevent endothelial dysfunction induced by ischemia and reperfusion in the human forearm vasculature.
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.
Luca
Mary Clare
MC
Mount Sinai Hospital, Toronto, ON, Canada.
Liuni
Andrew
A
DiFabio
Jonathan
J
Gori
Tommaso
T
Parker
John D
JD
D000328:Adult; D000584:Amiloride / Q000008:administration & dosage / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008297:Male; D017534:Radial Artery / Q000187:drug effects / Q000503:physiopathology; D015427:Reperfusion Injury / Q000503:physiopathology*; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D000806:Angiotensin-Converting Enzyme Inhibitors; D026941:Sodium Channel Blockers; D000584:Amiloride; D002216:Captopril