Because endothelin-1 (ET-1) is believed to be an endogenous calcium-channel agonist, it was thought that it may affect not only vascular smooth muscle cells but also nerve activity. Intravenous injections of ET-1 (0.01 nmol) did not affect cardiovascular parameters or renal sympathetic activity. ET-1 (1 nmol) initially decreased blood pressure for a few minutes, and then caused an increase for 5-10 min. Blood pressure then returned to baseline but later there was a rise in pressure for more than 60 min. Sympathetic activity was markedly suppressed during the initial hypertensive phase but increased during the later phase. Intracerebroventricular injections of ET-1 increased blood pressure even with the small dose (0.01 nmol). The increase was maintained for about 10 min, and returned to baseline. It then decreased abruptly with marked bradycardia, and finally returned to the baseline 60-90 min later. These results indicate that ET-1 affects not only the vascular smooth muscle but also the autonomic nervous system to influence cardiovascular functions.