Effects of a competitive antagonist of bradykinin on blood pressure and renal blood flow in anesthetized rats.
To examine a possible role of endogenous bradykinin in the regulation of blood pressure (BP) and renal blood flow (RBF), a newly synthesized competitive antagonist of bradykinin (B4147) was studied in anesthetized rats. Also, the question of whether the hypotensive effect of the converting enzyme inhibitor, captopril, is mediated partly by an accumulation of endogenous bradykinin was considered. The intravenous infusion of B4147 (25 micrograms/min) inhibited the depressor effect of exogenous bradykinin (0.5 microgram, i.v.) by 69%. After an intravenous injection of B4147 at doses of 25, 50 and 100 micrograms, BP increased and RBF decreased in a dose-dependent fashion. The increase in BP was not blocked by pretreatment with an angiotensin II antagonist (1-Sar-8-Ile angiotensin II; 20 micrograms/kg per min) or an alpha 1-blocker (prazosin; 0.1 mg/kg). The administration of captopril (1 mg/kg) decreased mean BP from 110 +/- 3.5 to 71 +/- 1.9 mmHg (P less than 0.001). However, the injection of B4147 (50 micrograms) after the administration of captopril elicited an increase in BP of 43% of the initial decrease induced by captopril. These results suggest that the effects of B4147 on BP and RBF are not mediated through angiotensin II or sympathetic alpha 1-stimulation. Endogenous bradykinin could contribute to the maintenance of BP and RBF in anesthetized rats, probably counter-balancing the vasoconstrictor mechanisms. It is also suggested that bradykinin may partly participate in the acute hypotensive effect induced by the converting enzyme inhibitor captopril.
Seino
M
M
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Abe
K
K
Nushiro
N
N
Omata
K
K
Kasai
Y
Y
Yoshinaga
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D005463:Fluoroacetates; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D005463:Fluoroacetates; C050396:B 4146; D002216:Captopril; D001920:Bradykinin