Effect of diazoxide on serum and tissue electrolyte levels in rats with deoxycorticosterone acetate-induced hypertension.

Effects of diazoxide, a benzothiadiazine derivative, on the blood pressure, excretion of Na+, K+, and Ca2+, and the levels of these electrolytes in serum, kidney, and aorta were studied in rats with deoxycorticosterone acetate (DOCA)-induced hypertension in comparison with rats treated with hydrochlorothiazide. After a lateral nephrectomy, 5 mg kg-1 of DOCA was injected subcutaneously three times a week. Drinking water for the rats injected with DOCA contained 1% NaCl. Systolic blood pressure in the DOCA-induced hypertensive rats became about 170 mmHg, with associated elevation of serum level of Na+ 7 weeks after the treatment, whereas that in the normotensive rats was about 100 mmHg. In the DOCA-hypertensive rats, urinary output, and renal excretion of Na+ and Ca2+ increased, and aortic tissue level of Ca2+ decreased as compared with those in the normotensive rats. After 7 weeks of the treatment, diazoxide (10 mg kg-1) or hydrochlorothiazide (10 mg kg-1) was injected intravenously. Diazoxide decreased the blood pressure in both DOCA-hypertensive and normotensive rats, whereas hydrochlorothiazide decreased it only in the DOCA-hypertensive rats. Diazoxide recovered the tissue aortic Ca2+ level that had been decreased by hypertension to that in the normotensive rats. Diazoxide may improve Ca2+ perturbation in the vascular smooth muscle due to DOCA-induced hypertension.