Affiliation:
1. From the Cardiovascular Sciences Research Group, Departments of Pharmacology and Therapeutics (P.B.A., M.J.L.) and Cardiology (R.M.G.-M., A.M.S.), University of Wales College of Medicine, Cardiff, UK.
Abstract
Background
ACE inhibitors exert both acute and chronic beneficial effects on cardiac function (eg, remodeling, diastolic dysfunction) in experimental studies and in patients. They inhibit the formation of angiotensin II as well as the degradation of endogenous bradykinin. We recently reported that bradykinin induces selective left ventricular (LV) relaxant effects in isolated hearts via the release of nitric oxide. The present study examined the direct effects of interaction between the ACE inhibitor captopril and endogenous bradykinin on cardiac contractile function.
Methods and Results
Isolated ejecting guinea pig hearts were studied under conditions of constant loading and heart rate. LV pressure was monitored by a 2F micromanometer-tipped catheter. Captopril (1 μmol/L, n=9) caused a progressive acceleration of LV relaxation without significantly affecting early systolic parameters (eg, LV dP/dt
max
) or coronary flow. These effects were inhibited by the nitric oxide scavenger hemoglobin (1 μmol/L, n=5) or by the B
2
-kinin receptor antagonist HOE140 (10 nmol/L, n=5). In the presence of captopril, bradykinin (0.1 nmol/L, n=6) markedly accelerated LV relaxation (significantly more than captopril alone), whereas bradykinin alone (0.1 nmol/L, n=6) had no effect.
Conclusions
These data indicate that the ACE inhibitor captopril causes an acute and selective enhancement of LV relaxation independent of changes in coronary flow, probably via an endogenous bradykinin/nitric oxide pathway.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
52 articles.
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