Comparison of angiotensin converting enzyme and renin inhibition in rats following myocardial infarction.
Renal and systemic hemodynamics were studied in rats 1 month after induction of myocardial infarction by ligation of the left coronary artery. The mean arterial pressure, heart rate, and cardiac index were not different from controls, but there were striking elevations in heart weight (p < 0.001), left ventricular end diastolic pressure (p < 0.002), and renal vascular resistance (p < 0.01). Renal blood flow and the percent of cardiac output perfusing the kidneys were reduced by 18% (p < 0.01) and 14% (p < 0.01), respectively. Acute angiotensin inhibition was studied at a dose of the converting enzyme inhibitor, enalapril, or the renin inhibitor, CP71362, that lowered the mean arterial pressure by 15 mm Hg in normal rats. In normal rats, enalapril and CP71362 were without effect on renal blood flow (RBF), renal vascular resistance (RR), and RBF as a percent of cardiac output. However, in rats with myocardial infarction, enalapril and CP71362 increased the RBF and RBF as a percent of cardiac output and lowered the RR to levels similar to normal controls (p < 0.02). Enalapril and CP71362 were equally effective in reducing the left ventricular end-diastolic pressure and total peripheral resistance in rats with myocardial infarction. These data demonstrate significant intrarenal vasoconstriction following myocardial infarction in the absence of detectable changes in mean arterial pressure or cardiac index. Converting enzyme inhibition or renin inhibition had similar beneficial effects on cardiorenal function, suggesting that both classes of compounds act by a similar mechanism to improve renal hemodynamics in congestive heart failure.
Mento
P F
PF
Department of Medicine, North Shore University Hospital, Manhasset, NY 11030.
Maita
M E
ME
Murphy
W R
WR
Holt
W F
WF
Wilkes
B M
BM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology; D004656:Enalapril / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008863:Microspheres; D009203:Myocardial Infarction / Q000503:physiopathology*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D000092502:Renin Inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D009842:Oligopeptides; D000092502:Renin Inhibitors; C060149:CP 71362