Lack of contribution of circulatory kinin elevated by captopril to induce hypotension in normotensive and hypertensive rats.
Captopril (10 mg/kg, i.p.) increased the arterial bradykinin (BK) level (Art-BK) of non-treated Sprague-Dawley rats (SD), determined by an ELISA, from 10.8 +/- 3.2 pg/ml to 32.9 +/- 5.4 pg/ml significantly (p < 0.05, n = 6). Intravenous infusion of BK (100-3000 ng/kg/min) dose-dependently increased heart rate (HR) and decreased mean blood pressure (MBP), the former at lower doses than the latter, and the hypotensive response became significant at 3000 ng/kg/min. Art-BK determined during infusion of the lowest dose of BK (100 ng/kg/min) was 12 times the endogenous Art-BK after captopril administration. In spontaneously hypertensive rats, Wistar Kyoto rats, and deoxycorticosterone acetate-salt treated hypertensive rats, Art-BK (450-1280 pg/ml) determined during intravenous BK-infusion (1000-3000 ng/kg/min), which induced significant hypotension, was 20 to 100 times the endogenous Art-BK (4.5-64 pg/ml) with captopril treatment. These results suggest that the increased Art-BK due to inhibition of kinin degradation by captopril could not account for the hypotension due to this angiotensin converting enzyme inhibitor in normotensive and hypertensive rats.
Majima
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Katori
M
M
Ogino
M
M
Saito
M
M
Sugimoto
K
K
Adachi
K
K
Ohno
T
T
Sunahara
N
N
Katoh
K
K
Tatemichi
N
N
Takei
Y
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000097:blood* / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D003900:Desoxycorticosterone; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007022:Hypotension / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D003900:Desoxycorticosterone; D002216:Captopril; D001920:Bradykinin