Endothelin enhances and inhibits adrenal catecholamine release in deoxycorticosterone acetate-salt hypertensive rats.

Abstract

Endothelin (ET) and the sympathoadrenal system contribute to the development and maintenance of deoxycorticosterone acetate (DOCA)-salt hypertension. ET can act directly on the adrenal medulla to enhance the release of catecholamines. In addition, the level of ET peptide is increased in the adrenal glands of DOCA-salt hypertensive rats. Therefore, we tested the hypothesis that ET enhances adrenal medullary catecholamine release during DOCA-salt hypertension. The infusion of exogenous ET-1 into an isolated, perfused adrenal gland preparation resulted in an increase in the basal release of norepinephrine (NE) and epinephrine (EPI) in control and DOCA-salt hypertensive rats. Nerve-stimulated (0.3 Hz) release of NE was significantly inhibited during ET-1 infusion in the DOCA-salt hypertensive rats but not in the control rats. The role of endogenous ET on basal and nerve-stimulated NE and EPI release was also examined. An infusion of either BQ-123 (10(-7) mol/L), an ET(A) receptor antagonist, or BQ-788 (10(-7) mol/L), an ET(B) receptor antagonist, did not alter basal NE or EPI release in either control or DOCA-salt hypertensive rats. BQ-788 did not alter nerve-stimulated release of NE and EPI. In contrast, the nerve-stimulated release of EPI, but not NE, was enhanced during BQ-123 infusion in DOCA-salt hypertensive rats. Nerve-stimulated NE and EPI release was unaffected by BQ-123 in the control rats. These data suggest that ET can stimulate adrenal medullary catecholamine release in normotensive and DOCA-salt hypertensive rats. However, ET also inhibits adrenal medullary catecholamine release in DOCA-salt hypertensive rats.