Kinin-Mediated Antihypertensive Effect of Captopril in Deoxycorticosterone Acetate–Salt Hypertension

Abstract

Abstract 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 B 2 receptor antagonist Hoe 140 (500 μg/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.