VASCULAR RENIN IN THE GUINEA-PIG - SUPPRESSION BY THE RENIN INHIBITORREMIKIREN

Angiotensin I and II are generated by the vascular wall. Whether this generation depends on renin or on other enzymes is debated. We tested the hypothesis that remikiren, a highly specific inhibitor of human an d guinea pig renin, may inhibit the vascular renin-angiotensin system. Isolated hindquarters from guinea pigs were perfused with an artifici al medium, and angiotensin I and II release was measured by high-perfo rmance liquid chromatography and radioimmunoassay. Guinea pig hindquar ters released angiotensin I (23.8+/-5.6 fmol/30 min; n=13) and angiote nsin II (95.2+/-19 fmol/30 min; n=13) spontaneously. Inhibition of the angiotensin I-converting enzyme by captopril (10 nmol/mL) suppressed angiotensin II by 85% and increased angiotensin I by 352% (n=5, P<.05) . Infusion of remikiren (1.6 nmol/mL) in addition to captopril decreas ed angiotensin I release by 68% (P<.05 versus captopril alone, n=5 eac h). We conclude that renin generates angiotensin I in an isolated guin ea pig resistance vessel bed. Our study demonstrates that renin rather than nonrenin enzymes is responsible for the major part of vascular a ngiotensin formation.