Calcium Channel Blockers Reverse the Sustained Elevation of Blood Pressure Induced by Chronic Infusion of Endothelin in Conscious Rats

YASUJIMA, M., ABE, K., KANAZAWA, M., YOSHIDA, K., SATO, M., TAKEUCHI, K., TSUNODA, K., KUDO, K., KOHZUKI, M., OMATA, K., YABE, T., HIWATARI, M., SATO, T. and YOSHINAGA, K. Calcium Channel Blockers Reverse the Sustained Elevation of Blood Pressure Induced by Chronic Infusion of Endothelin in Conscious Rats. Tohoku J. Exp. Med., 1990, 160 (2), 157-165 — To determine whether endothelin could act as a circulating hormone in the regulation of blood pressure and sodium-water excretion, we assessed the chronic effects of synthetic endothelin on systolic blood pressure, urine volume and urinary sodium excretion in conscious rats, and also evaluated the effects of benidipine or nilvadipine, newly developed calcium channel blockers, in rats infused chronically with synthetic endothelin. Continuous infusion of endothelin at a rate of 60 μg/kg/day into the jugular vein via osmotic minipumps induced a significant increase in systolic blood pressure, but did not induce any significant changes in urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. On the contrary, the infusion of endothelin at a rate of 60 μg/kg/day did not induce any significant changes in systolic blood pressure, urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. When 6 mg/kg/day of benidipine or 10 mg/kg/day of nilvadipine was administered simultaneously with 60 μg/kg/day of endothelin, the systolic blood pressure rose on Day I to only 137.0±2.4 mmHg (p<0.05) and 119.7±5.9 mmHg (p<0.05) compared to the rise to 163.8±4.7 mmHg 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. The present results suggest that endothelin can act as a circulating hormone and might be involved in the regulation of blood pressure. In addition, they clearly demonstrate that the calcium channel blockers attenuate the elevation of blood pressure induced by endothelin, although the exact mechanisms whereby these drugs could interact remain to be determined. —endothelin; calcium channel blockers; blood pressure regulation; conscious rats.