Comparison of renal hemodynamic effect of ramiprilat to captopril; possible role of kinins.
The purpose of this study was to compare a lipophilic angiotensin-converting enzyme (ACE) inhibitor, ramiprilat, to the hydrophilic agent, captopril, with respect to its efficacy in decreasing blood pressure (BP) and increasing renal blood flow (RBF). Fifty-seven anesthetized rabbits were instrumented for monitoring BP and RBF. Separate groups of experiments were conducted in which the inhibitors were given i.v. and intrarenal i.a. In Group I, ramiprilat (1 mg/kg and 0.5 mg/kg/hr i.v.) and captopril (2 mg/kg and 1 mg/kg/hr i.v.) decreased BP and increased RBF to the same extent. Both ACE inhibitors abolished the pressor effect and greatly attenuated the renal vasoconstrictor response to exogenous angiotensin I. When the ACE inhibitors were administered in graded doses i.a. (Group II), they caused a similar increase in RBF and decrease in BP as when given i.v. Ramiprilat was about twice as potent as captopril by either route of administration. In the presence of an i.a. infusion of the bradykinin antagonist HOE 140 (Group IV), the effect of ramiprilat and captopril given i.a. on BP and RBF was not different than in Group II. In Group V, the angiotensin II receptor antagonist, losartan, decreased BP and increased RBF. There was little further effect on RBF seen with ramiprilat, but captopril caused some additional renal vasodilatation after losartan. A small further fall in BP was obtained with both agents after losartan. In conclusion, ramiprilat and captopril, despite marked solubility differences, produced a similar renal hemodynamic effect and decrease in BP. No significant difference was seen in the presence of bradykinin antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
K
K
Department of Pharmacology, University of Minnesota Medical School, Minneapolis.
Zimmerman
B G
BG
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D007705:Kinins / Q000502:physiology*; D019808:Losartan; D008297:Male; D011817:Rabbits; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D007705:Kinins; D013777:Tetrazoles; C052549:ramiprilat; C065679:icatibant; D002216:Captopril; D019808:Losartan; D017257:Ramipril; D001920:Bradykinin