Renal hemodynamic effects of nonhypotensive doses of angiotensin-converting enzyme inhibitors in hypertension and heart failure rats.
Both circulating and local renin-angiotensin systems (RAS) may contribute to cardiovascular homeostasis under normal and pathophysiologic conditions. They may also play a role in the effects of angiotensin-converting enzyme (ACE) inhibitors. In the present study, we compared systemic and regional hemodynamic effects of nonhypotensive doses of captopril and enalaprilate in normal rats, spontaneously hypertensive rats (SHR), and rats with heart failure due to myocardial infarction (MI). Enalaprilate (0.1 mg/kg) or captopril (3 mg/kg) was injected intravenously (i.v.) in conscious rats equipped with miniature Doppler flow probes on renal and mesenteric artery and abdominal aorta or an electromagnetic flow probe on the ascending aorta to measure cardiac output (CO). This resulted in a shift of the angiotensin-I (ANG I) dose-pressor curve (ED50 of ANG I after saline 0.21 +/- 0.33 micrograms, enalaprilate 1.45 +/- 0.26 micrograms, captopril 2.38 +/- 0.73 micrograms; mean +/- SEM; n = 6-12). In the systemic hemodynamic groups, no significant changes in mean arterial pressure (MAP), CO, or total peripheral resistance (TPR) were observed. In the regional hemodynamic groups, enalaprilate caused a slight (-8 +/- 1 mm Hg) reduction in MAP in normal rats. Resistance in the hindquarters was not affected by ACE inhibitors, whereas only enalaprilate reduced mesenteric resistance in MI rats. In contrast, renal resistance was reduced and renal blood flow (RBF) increased after captopril in normal and MI rats and after enalaprilate in MI rats. Effects were greatest in MI rats (RBF: saline -0.05 +/- 1.9%, enalaprilate 10.3 +/- 2.4%, captopril 10.1 +/- 2.0%).(ABSTRACT TRUNCATED AT 250 WORDS)
Nelissen-Vrancken
H J
HJ
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
Struijker-Boudier
H A
HA
Smits
J F
JF
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D015773:Enalaprilat / Q000008:administration & dosage / Q000494:pharmacology; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007275:Injections, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D015773:Enalaprilat