Enhancement of left ventricular relaxation in the isolated heart by an angiotensin-converting enzyme inhibitor.
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.


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 mumol/L, n = 9) caused a progressive acceleration of LV relaxation without significantly affecting early systolic parameters (eg, LV dP/dtmax) or coronary flow. These effects were inhibited by the nitric oxide scavenger hemoglobin (1 mumol/L, n = 5) or by the B2-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.
Anning
P B
PB
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff, UK.
Grocott-Mason
R M
RM
Lewis
M J
MJ
Shah
A M
AM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D016276:Ventricular Function; D016277:Ventricular Function, Left / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D001920:Bradykinin