Abstract
YASUJIMA, M., ABE, K., KANAZAWA, M., YOSHIDA, K., KOHZUKI, M., TAKEUCHI, K., TSUNODA, K., KUDO, K., HIWATARI, M., SATO, T. and YOSHINAGA, K. Antihypertensive Effect of Captopril and Enalapril in Endothelin-Infused Rats. Tohoku J. Exp. Med., 1991, 163 (3), 219-227 - Comparative effects of angiotensin converting enzyme inhibitors and calcium channel blockers were assessed in rats infused chronically with synthetic endothelin. When 50mg/kg/day of captopril orally or 6mg/kg/day of enalapril intraperitoneally was administered simultaneously with 60μg/kg/day of endothelin, the systolic blood pressure was on Day 1142.7±5.9mmHg (p<0.05) or 128.7±6.7mmHg (p<0.05), respectively, compared to the rise to 163.8±4.7mmHg when endothelin alone was infused. The antihypertensive effect of captopril or enalapril was sustained for the entire experimental period and was not associated with a significant change in urinary sodium excretion, whereas both drugs induced a significant increase in urine volume. Chronic infusion of angiotensin II intraperitoneally at a subpressor dose (400μg/kg/day) reversed the antihypertensive effect of captopril in endothelin-infused rats. When 6mg/kg/day of benidipine or 10mg/kg/day of nilvadipine orally was administered simultaneously with 60μg/kg/day of endothelin, the systolic blood pressure was on Day 1137.0±2.4mmHg (p<0.05) or 119.7±5.9mmHg (p<0.05), respectively, compared to the rise when endothelin alone was infused. The antihypertensive effect of benidipine or nilvadipine was sustained for the entire experimental period and was not associated with any significant changes in urine volume and urinary sodium excretion. These results indicate that the reduced sensitivity of the peripheral arteries to endothelin may be involved in the mechanism of the hypotensive action of angiotensin converting enzyme inhibitors, dependent on the suppressed angiotensin II formation.
