v"-[l-(ft.S)-carboxyl-3-phenylpropyl]-Ala-Ala-Phep-aminobenzoate (cFP-AAF-pAB), an active-site-directed inhibitor of metalloendopeptidase-24.15, has been shown to lower blood pressure, increase cardiac output and renal blood flow, and potentiate the intravenous bradykinin-induced vasodepressor response. Because in vivo cFP-AAF-pAB can be converted to A41-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala (a compound with angiotensin converting enzyme inhibitory activity) by metalloendopeptidase-24.11, it

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... possible that some of its effects are due to angiotensin converting enzyme inhibition. In the present study, we questioned (1) whether cFP-AAF-pAB inhibits angiotensin converting enzyme in vivo and (2) whether cFP-AAF-pAB has renal effects that are independent of its conversion to an angiotensin converting enzyme inhibitor. cFP-AAF-pAB alone (3 junol in 300 pL per rat) almost abolished the blood pressure response to angiotensin I, suggesting that in vivo it inhibits angiotensin converting enzyme. In rats pretreated with a high dose of enalaprilat (1 mg/kg), cFP-AAF-pAB had no further effect on blood pressure, renal blood flow, or potentiation of the vasodepressor response to bradykinin but still increased glomerular filtration rate by 44±9% (P<.01); urine volume increased by 118±10% (P<.001), urinary sodium excretion by 230±31% (P<.001), urinary potassium excretion by 68±14% (P<.01), and urinary cyclic GMP by 55±18% (P<.01). All of these changes were significant compared with enalaprilat/vehicle-treated rats. Fractional excretion of sodium and potassium did not differ from controls. These results suggest that effects of cFP-AAF-pAB on blood pressure, renal blood flow, and potentiation of the vasodepressor response to bradykinin could be mediated by angiotensin converting enzyme inhibition. However, some of the renal effects may be due to inhibition of metalloendopeptidase-24.15 or peptidases other than angiotensin converting enzyme. (Hypertension. 1994;23 [suppl I]:I-235-I-239.) Key Words • membrane metalloendopeptidase • protease inhibitors • dipeptidyl peptidases • angiotensin converting enzyme inhibitors • kininase II • enalaprilat • renal circulation • hemodynamics by guest on July 22, 2018 http://hyper.ahajournals.org/ Downloaded from by guest on July 22, 2018 http://hyper.ahajournals.org/ Downloaded from X P Yang, S Saitoh, A G Scicli, E Mascha, M Orlowski and O A Carretero rats. Effects of a metalloendopeptidase-24.15. Inhibitor on renal hemodynamics and function in