Development of a high renin model of hypertension in the cynomolgus monkey.
Hypertension was produced in cynomolgus monkeys by reducing blood flow to the left kidney by 60% via renal artery stenosis (2-kidney, 1-clip). Significant increases in mean arterial blood pressure (MABP) were observed within two to three weeks. Maximum increase (from 95 +/- 6 mmHg to 130 +/- 7 mmHg) occurred at about four to six weeks following renal artery stenosis and was sustained for more than 24 weeks. Plasma renin activity (PRA) was elevated concomitantly with the increase in MABP. PRA was raised to 42 +/- 3 ng angiotensin I/ml/hr six weeks after renal artery stenosis from a control PRA of 3 +/- 0.7 ng angiotensin I/ml/hr. At six months post renal artery stenosis, PRA was 33.4 +/- 4.2 ng angiotensin I/ml/hr. The angiotensin II (AII) receptor antagonist saralasin, the angiotensin I converting enzyme inhibitor captopril, and the renin inhibitor CGP 38,560 produced sustained reductions in MABP. The antihypertensive response to the renin inhibitor CGP 38,560 was associated with a reduction in PRA of greater than 99%, and a greater than 90% reduction in immunoreactive AII. These studies demonstrate that high-renin hypertension can be induced in the cynomolgus monkey. This pathological model provides a useful method for investigating the antihypertensive effects of agents which antagonize the renin-angiotensin system in a nonhuman primate.
Panek
R L
RL
Department of Pharmacology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Ryan
M J
MJ
Weishaar
R E
RE
Taylor
D G
DG
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D008252:Macaca fascicularis; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D012078:Renal Artery Obstruction / Q000150:complications; D012083:Renin / Q000097:blood*; D012504:Saralasin / Q000494:pharmacology; D000092502:Renin Inhibitors
D000804:Angiotensin II; D002216:Captopril; D009842:Oligopeptides; D012083:Renin; D012504:Saralasin; D000092502:Renin Inhibitors; C060150:CGP 38560