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.