Development of a High Renin Model of Hypertension in the Cynomolgus Monkey

Abstract

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 320.7 ng angiotensin I/ml/hr. At six months post renal artery stenosis, PRA was 33.424.2 ng angiotensin I/ml/hr. The angiotensin I1 (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 >99%, and a >90% reduction in imnunoreactive 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 reninangiotensin system in a nonhuman primate.

Key Words:

• Hypertension
• Renin-Angiotensin System
• Angiotensin II