Endothelin-1 enhances thymocyte proliferation in monolaterally adrenalectomized rats with contralateral adrenocortical regeneration

Endothelins (ETs) are a family of vasoactive peptides widely distributed in the body systems, where they exert pleiotropic biological effects, acting through two main subtypes of receptors, named ETA and ETB. Evidence indicates that ET-1 plays a permissive role in the development of neural crest-derived structures, among which are the epithelial cells of the thymus. These cells are known to control proliferation and differentiation of thymocytes, a process requiring adequate levels of glucocorticoids. Therefore, we have investigated the effects of ET-1, that binds both ETA and ETB receptors, on thymocyte proliferation in monolaterally adrenalectomized rats with contralateral enucleated adrenal at day 4 and 8 of regeneration, when glucocorticoid production is very low and, respectively, rather normal. Metaphase index (percentage of metaphase arrested cells) of thymocytes is the lowest at day 4 of regeneration, and markedly rose at day 8, thereby confirming the need of sizable levels of circulating glucocorticoid for the maintenance of a normal rate of thymocyte proliferation. ET-1 markedly increased the mitotic index of thymocytes at both times of adrenal regeneration. At day 8 of regeneration, the ETA-receptor antagonist BQ-123 markedly lowered mitotic index of thymocytes, and annulled its ET-1-evoked raise. Conversely, the ETB-receptor antagonist BQ-788 was ineffective. Collectively, these findings clearly indicate that endogenous ETs, through the activation of ETA receptors, are involved in the maintenance and stimulation of thymocyte proliferation in the adult rat, thereby playing a possibly important role in the modulation of the immune-system function