The acute administration of either amiloride or captopril does not prevent endothelial dysfunction induced by ischemia and reperfusion in the human forearm vasculature

• Published in: Canadian journal of physiology and pharmacology 2010-10, Vol.88 (10), p.996-1001
• Main Authors: Luca, Mary Clare, Liuni, Andrew, DiFabio, Jonathan, Gori, Tommaso, Parker, John D
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Adult; Amiloride; Amiloride - administration & dosage; Amiloride - pharmacology; angiotensin-converting enzyme inhibitor; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Biological and medical sciences; Blood Flow Velocity - drug effects; Blood Flow Velocity - physiology; Captopril; Captopril - administration & dosage; Captopril - pharmacology; Care and treatment; Complications and side effects; Cross-Over Studies; dilatation véhiculée par le débit; Dosage and administration; Dose-Response Relationship, Drug; Double-Blind Method; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; endothélium; flow-mediated dilation; Forearm - blood supply; Fundamental and applied biological sciences. Psychology; Humans; inhibiteur de l'enzyme de conversion de l'angiotensine; inhibiteur de l'échangeur sodium-hydrogène; Ischemia; ischémie; Male; Radial Artery - drug effects; Radial Artery - physiopathology; reperfusion; Reperfusion Injury - physiopathology; Sodium Channel Blockers - administration & dosage; Sodium Channel Blockers - pharmacology; sodium-hydrogen exchange inhibitor; Studies; Tissues; Vasodilation - drug effects; Vasodilation - physiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Young Adult
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/Y10-081

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.