Vascular renin in the guinea pig. Suppression by the renin inhibitor remikiren.
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 and guinea pig renin, may inhibit the vascular renin-angiotensin system. Isolated hindquarters from guinea pigs were perfused with an artificial medium, and angiotensin I and II release was measured by high-performance liquid chromatography and radioimmunoassay. Guinea pig hindquarters released angiotensin I (23.8 +/- 5.6 fmol/30 min; n = 13) and angiotensin 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 decreased angiotensin I release by 68% (P < .05 versus captopril alone, n = 5 each). We conclude that renin generates angiotensin I in an isolated guinea pig resistance vessel bed. Our study demonstrates that renin rather than nonrenin enzymes is responsible for the major part of vascular angiotensin formation.
Hilgers
K F
KF
Department of Medicine, University of Erlangen, Germany.
Fischli
W
W
Veelken
R
R
Mann
J F
JF
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D006614:Hindlimb / Q000098:blood supply; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011863:Radioimmunoassay; D012083:Renin / Q000378:metabolism*; D000092502:Renin Inhibitors
D000803:Angiotensin I; D000804:Angiotensin II; D002216:Captopril; D007093:Imidazoles; D012083:Renin; D000092502:Renin Inhibitors; C065581:remikiren