The acute renal actions of angiotensin converting enzyme inhibitors in the sodium-depleted conscious primate are mediated by inhibition of the renin-angiotensin system.
The purpose of this study was to determine if the changes in renal function acutely produced by an inhibitor of angiotensin converting enzyme (ACE) in the sodium-depleted conscious marmoset can be explained primarily by blockade of the renin-angiotensin system. Intravenous injection of a dose of the ACEI, enalaprilate (2 mg/kg), that produced a maximal lowering of blood pressure (BP), also decreased renal vascular resistance and increased renal blood flow. Glomerular filtration rate was unchanged by enalaprilat, leading to a fall in the filtration fraction. In comparison, a dose of the renin inhibitory monoclonal antibody, R-3-36-16 (0.1 mg/kg), that also produced a maximal fall in BP, produced similar changes in renal hemodynamics to those observed after administration of the ACEI. Combined administration of 2 mg/kg enalaprilat and 0.1 mg/kg R-3-36-16 produced changes in BP and renal hemodynamics similar to those produced by the same doses of either agent administered alone. Enalaprilat (2 mg/kg) significantly increased urine volume (UV) and urinary sodium excretion (UNaV). In contrast, these parameters were not significantly altered by 0.1 mg/kg R-3-36-16. However, when given at a 10-fold higher dose, the monoclonal antibody produced an increase in UNaV and UV identical to that produced by the ACEI alone. Enalaprilat did not increase UV and UNaV excretion to a greater extent than the high dose of the renin inhibitory antibody. These results demonstrate that acute administration of an ACEI affects BP and renal function in the sodium-depleted conscious primate primarily by inhibition of the renin-angiotensin system.
Humke
U
U
Cardiovascular Research Department, CIBA-GEIGY Ltd., Basel, Switzerland.
Levens
N
N
Wood
J
J
Hofbauer
K
K
D000804:Angiotensin II / Q000096:biosynthesis / Q000097:blood / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal; D002144:Callithrix; D003243:Consciousness; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000502:physiology* / Q000652:urine; D014556:Urine; D000092502:Renin Inhibitors
D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D000911:Antibodies, Monoclonal; D015773:Enalaprilat; D012083:Renin; D012964:Sodium; D000092502:Renin Inhibitors