Endogenous endothelins are not involved in the maintenance and stimulationof the adrenal growth in immature and young rats

The effects of endothelin (ET) - 1 and its receptor (ETA and ETB) antagonis ts on the proliferative activity of adrenal zona glomerulosa (ZG) have been investigated in immature (19-day old) and young (38-day old) rats. The ani mals were given intraperitoneal injections of the peptides every 12 h for t wo days, and were decapitated 12 h before last injection. Rats received 180 min before autopsy 1 mu g/g vincristine, and ZG mitotic index (% of metaph ase-arrested cells) was evaluated. ET-1 (0.5 nmol/100g) increased ZG mitoti c index in both age-groups of rats. The ETA-receptor antagonist BQ- 123 (5 nmol/100 g) annulled this effect of ET-1, while the ETB-receptor antagonist BQ-788 (5 nmo1/100g) was ineffective, thereby confirming that ETA receptor s mediate the ZG proliferogenic action of ET-1 in rats. BQ-123 did not alte r basal mitotic index of ZG, while BQ-788 doubled it; the simultaneous admi nistration of the two antagonists did not change basal mitotic index. We in terpret these last findings as indicating that (i) basal ETA activation by endogenous ETs is not needed for the maintenance of a normal ZG proliferati ve activity during age-dependent adrenal growth; and (ii) the occupancy of ETB receptors by BQ-788 allows endogenous ETs to evoke an exceedingly high activation of ETA receptors, which may be able to enhance ZG-cell prolifera tion.