Angiotensin converting enzyme inhibition by captopril influences cardiac work in healthy hearts.
Although beneficial effects of angiotensin converting enzyme (ACE) inhibition have been demonstrated in ill (ischemic, failing) hearts, it has not been proved that ACE inhibition induces changes in healthy hearts. The question is of clinical relevance, as many hypertensive patients do not display cardiac damage at the onset of treatment with ACE inhibitors, and possible changes in cardiac work might turn out more or less advantageous in the development of hypertensive heart disease. In a refined working heart preparation allowing measurement of cardiac work, including the contribution of atrial work and paracrine cardiac regulation, effects of captopril on cardiac dynamics were assessed. Coronary overflow of bradykinin, norepinephrine, and lactate was measured. Hearts were perfused for 20 min with vehicle or captopril at 3 x 10(-8), 3 x 10(-7), 3 x 10(-6), and 3 x 10(-5) mol/L. At the highest concentration, captopril increased coronary flow. Extending previous studies, the present study demonstrates that, in a concentration-dependent manner, captopril decreased oxygen consumption and maximal left ventricular pressure although the bradykinin outflow was not affected. From these influences of the drug on cardiac work and metabolism in healthy hearts, a protective influence of captopril in acute, critical situations of cardiac malnourishment or cardiac overload may be derived.
Derad
I
I
Department of Internal Medicine, University of Lübeck, Germany. derad@kfg.mu-luebeck.de
Dendorfer
A
A
Dominiak
P
P
Fehm
H L
HL
Born
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D001920:Bradykinin; D009638:Norepinephrine