EFFECTS OF THE PROLONGED ADMINISTRATION OF SELECTIVE ETA-RECEPTOR ANDETB-RECEPTOR ANTAGONISTS ON THE RAT ADRENAL-CORTEX

The role of endogenous endothelins (ETs) in the functional regulation of the pituitary-adrenal axis (PAA) and in the maintenance of rat adre nal growth has been investigated. The daily subcutaneous injection of the selective ETA- and ETB-receptor antagonists, BQ-123 and BQ-788 (20 nmol/kg for 5 days), did not evoke any significant changes in the adr enal weight, as well as in the growth of adrenocortical zones and cell s, but it caused significant rises in the plasma concentrations of ACT H, aldosterone and corticosterone. However, the prolonged administrati on of the two antagonists inhibited the acute secretory responses of P AA to ET-1 (1.5 nmol/kg). In light of these findings, the following co nclusions are drawn: (i) endogenous ETs do not play a major role in th e physiological maintenance of rat adrenal growth; (ii) exogenous ET-I acutely stimulates rat PAA axis acting through both BQ-123- and BQ-78 8-sensitive ET receptors (ETA1 and ETB1); and (iii) the occupancy of E TA1 and ETB1 by the two ligands, probably allows endogenous ETs to bin d molecular variants of ET receptors (ETA2 and ETB2) whose prolonged a ctivation is able to stimulate rat PAA.