Kinin-mediated antihypertensive effect of captopril in deoxycorticosterone acetate-salt hypertension.
On the basis of evidence suggesting the activation of the kallikrein-kinin system in steroid-induced hypertension, we considered the possibility that the angiotensin-converting enzyme inhibitor captopril would lower the arterial blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats through kininase II inhibition. In conscious DOCA-salt hypertensive rats with intact kidneys (n = 6) or uninephrectomized rats (n = 5), the short-term administration of captopril (8 mg/kg IV) decreased mean blood pressure from 141 +/- 3 to 118 +/- 3 mm Hg (P < .05) and from 176 +/- 12 to 158 +/- 15 mm Hg (P < .05), respectively. The maximal effect of captopril was manifested between 40 and 50 minutes after its administration, and blood pressure remained depressed for at least 2 hours. The bradykinin B2 receptor antagonist Hoe 140 (500 micrograms/kg IV) abolished the antihypertensive effect of captopril in the DOCA-salt hypertensive rats, indicating kinin involvement. Losartan, an angiotensin type 1 receptor antagonist, had no effect on blood pressure in another group of DOCA-salt hypertensive rats (n = 9) and did not significantly change the response to captopril. No effect of the angiotensin-converting enzyme inhibitor was seen in normotensive control rats (n = 5), indicating the absence of a nonspecific hypotensive action of the drug. Plasma renin activity was lower in the DOCA-salt hypertensive rats (0.7 +/- 0.2 ng angiotensin I/mL per hour, n = 4) than in normotensive control rats (8.8 +/- 1.7, n = 4). The involvement of kinins in the antihypertensive effect of captopril in DOCA-salt hypertension supports the contention that the kallikrein-kinin system contributes to blood pressure regulation in this hypertension model.
Chen
K
K
Department of Pharmacology, University of Minnesota, Minneapolis, USA.
Zhang
X
X
Dunham
E W
EW
Zimmerman
B G
BG
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D007705:Kinins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects; D012965:Sodium Chloride; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D007705:Kinins; D000804:Angiotensin II; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C065679:icatibant; D002216:Captopril; D001920:Bradykinin