Enhanced blood pressure and renal hemodynamic effect of chronic versus acute lisinopril administration in the rabbit.
This study was aimed at evaluating the factors responsible for the marked renal hemodynamic effect of 6-day treatment with lisinopril. Blood pressure (BP) and renal blood flow (RBF) were monitored in six groups of rabbits. Animals treated with lisinopril for 6 days (Group I) had lower BP (77 +/- 3 mm Hg) than normal controls (Groups II/III, 106 +/- 3 mm Hg, P < .05) or those given lisinopril acutely (Group IV, 93 +/- 8 mm Hg, P < .05). In addition, RBF was higher in Group I (81 +/- 2 ml/min) than in Groups II/III (54 +/- 5 ml/min, P < .05) or Group IV (66 +/- 8 ml/min, P < .05). Intrarenal arterial infusion of a B2 bradykinin receptor antagonist, D-Arg-O-[Hyp-3-Thi-5,8-D-Phe-7]bradykinin, had no effect on either BP or RBF in Group I. Administration of lisinopril for 6 days also resulted in attenuation of the vasoconstrictor responses to renal nerve stimulation (Group V). Intravenous infusion of D-Arg-O-[Hyp-3-Thi-5,8-D-Phe-7]bradykinin had no effect on the responses to nerve stimulation in lisinopril-treated rabbits (Group V) or their controls (Group VI). Moreover, D-Arg-O-[Hyp-3-Thi-5,8-D-Phe-7]bradykinin given i.v. did not alter the BP or RBF in Groups V and VI. The results indicate that angiotensin converting enzyme inhibition over a 6-day period is more effective than acute inhibition in lowering BP and dilating the renal vascular bed. The use of bradykinin antagonists did not indicate kinin involvement in the long-term effect of lisinopril on BP and RBF.
Hajj-Ali
A F
AF
Department of Pharmacology, University of Minnesota, Minneapolis.
Zimmerman
B G
BG
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007668:Kidney / Q000187:drug effects*; D017706:Lisinopril; D008297:Male; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D017706:Lisinopril