Mechanisms and receptor subtypes involved in the stimulatory action of endothelin-1 on rat adrenal zona glomerulosa

Endothelin (ET)-1 is the prototype of a family of 21-amino acid residue hyp ertensive peptides, acting through two subtypes of receptors, named ETA and ETB. ETs and their receptors are expressed in the adrenal cortex and medul la, and ET-1 enhances both corticosteroid and catecholamine release. ET-1 c oncentration-dependently (from 10(-11) to 10(-8) M) increased aldosterone s ecretion of both dispersed rat zona glomerulosa (ZG) cells and adrenal slic es containing a core of medullary chromaffin tissue, but the response of th e latter preparations was significantly more intense than that of the forme rs. The stimulatory effect of 10(-8) M ET-1 on dispersed ZG cells was block ed by the ETB-receptor antagonist BQ-788 (10(-7) M), but not by the ETA-rec eptor antagonist BQ-123 (10(-7) M); conversely, both ET-receptors antagonis ts counteracted aldosterone response of adrenal slices to ET-1. The beta-ad renoceptor antagonist I-alprenolol (10(-6) M) did not affect aldosterone re sponse of dispersed ZG cells to ET-1 (10(-8) M), but it significantly lower ed that of adrenal slices. I-Alprenolol also counteracted the aldosterone r esponse of adrenal slices to the pure activation of ETB or ETA receptors, a s obtained by using the selective ETB-receptor agonist BQ-3020 (10-8 M) or ET-1 (10-8 M) plus BQ-788 (10(-7) M). ET-1 concentration-dependently (from 10(-9) to 10(-8)/10(-7) M) stimulated catecholamine release by adrenal slic es, and the effect was counteracted by both BQ-123 and BQ-788 (10-7 M). Col lectively, our findings suggest that, when the integrity of adrenal tissue is preserved, a two-fold mechanism underlies the aldosterone secretagogue a ction of ET-1 in the rat: i) a direct mechanism mediated by ETB receptors l ocated on ZG cells; and ii) an indirect mechanism involving the ETA and ETB receptor-mediated local release of catecholamines, which in turn stimulate ZG cells in a paracrine manner.