Affiliation:
1. From the Cardiovascular Research Institute, Department of Medicine, Allegheny General Hospital, Pittsburgh, Pa.
Abstract
Background
—
ACE inhibitors have been used extensively in heart failure, where they induce systemic vasodilatation. ACE inhibitors have also been shown to reduce ischemic events after myocardial infarction, although their mechanisms of action on the coronary circulation are less well understood. The purpose of the present study was to determine the effects and the mechanism of action of the ACE inhibitor enalaprilat and the AT
1
antagonist losartan on regional myocardial perfusion and coronary flow and vasodilator reserve in conscious dogs with pacing-induced dilated cardiomyopathy (DCM).
Methods and Results
—
Twenty-seven conscious, chronically instrumented dogs were studied during advanced stages of dilated cardiomyopathy, which was induced by rapid pacing. Enalaprilat (1.25 mg IV) improved transmural distribution (endocardial/epicardial ratio) at rest (baseline, 0.91±0.11; enalaprilat, 1.02±0.07 mL/min per g;
P
<0.05) and during atrial pacing (baseline, 0.82±0.11; enalaprilat, 0.98±0.07;
P
<0.05). Enalaprilat also restored subendocardial coronary flow reserve (CFR) (baseline CFR, 1.89±0.11; enalaprilat CFR, 2.74±0.33;
P
<0.05) in DCM. These effects were abolished by pretreatment with the NO synthase inhibitor nitro-
l
-arginine. The effects were recapitulated by the bradykinin
2
receptor agonist cereport but not by the AT
1
antagonist losartan.
Conclusions
—
The ACE inhibitor enalaprilat improves transmural myocardial perfusion at rest and after chronotropic stress and restores impaired subendocardial coronary flow and vasodilator reserve in DCM. The effects of enalaprilat were bradykinin mediated and NO dependent and were not recapitulated by losartan. These data suggest beneficial effects of ACE inhibitors on the coronary circulation in DCM that are not shared by AT
1
receptor antagonists.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
57 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献