Buffering action of endogenous nitric oxide on the adrenocortical secretagogue effect of endothelins is the rat

The secretagogue effect of endothelins (ETs) on the rat adrenal cortex is m ediated by the ETB receptor. ETB receptors are coupled with nitric oxide (N O) synthase (NOS), and NO is known to inhibit steroid-hormone secretion fro m adrenal cortex. We investigated whether ETB-mediated NO production interf eres with the stimulatory action of ETs on rat adrenal cortex. The selectiv e agonist of ETB receptor BQ-3020 concentration-dependentIy increased aldos terone secretion from dispersed zona glomerulosa (ZG) cells and corticoster one secretion from dispersed zona fasciculata-reticularis (ZF/R) cells, and the NOS inhibitor NG-nitro-L-arginine methylester (L-NAME) potentiated the effect of BQ-3020 in a concentration-dependent manner. The guanylate cycla se inhibitor Ly-83583, at a concentration suppressing guanylin-and L-argini ne-induced cyclic-GMP release from dispersed adrenocortical cells, did not affect the secretory response of ZG and ZF/R cells to BQ-3020. ET-I, an ago nist of both ETA and ETB receptors, stimulated the release of both aldoster one and corticosterone by in situ perfused rat adrenal gland. This effect w as potentiated by L-NAME and unaffected by Ly-83583. Collectively, our find ings allow us to suggest that endogenous NO exerts in vivo and in vitro a c yclic-GMP-independent buffering action on the ETB receptor-mediated adrenoc ortical secretagogue action of ETs.