Effects of endothelin-1 on the rat pituitary-adrenocortical axis under basal and stressful conditions.
Endothelins (ETs) and their receptor subtypes A and B (ETA and ETB) are expressed in the various components of the mammalian hypothalamo-pituitary-adrenal (HPA) axis, but their involvement in the functional regulation of HPA is controversial. To gain insight into this topic, we have investigated the effects of ET-1 and/or the specific antagonists of ETA and ETB receptors (BQ-123 and BQ-788, respectively) on the plasma concentrations of ACTH, corticosterone and aldosterone of non-stressed (control) and ether- or cold-stressed rats. The study of the effects of the administration of the two ET-receptor antagonists alone could provide informations about the possible action of endogenous ETs on the HPA axis. Exogenous ET-1 increased ACTH, corticosterone and aldosterone blood levels in control rats, as well as evoked a sizable enhancement of the HPA axis response to ether stress and a marked depression of the response to cold stress. BQ-123 and BQ-788 did not prevent the stimulatory effect of exogenous ET-1 in control rats, but when administered alone, raised the plasma concentrations of ACTH, corticosterone and aldosterone. Both ET-receptor antagonists magnified the HPA axis response to ether and cold stresses, but their effect was not counteracted by exogenous ET-1. Although very difficult to interpret, our present findings allow us to conclude that endogenous ETs play a role in the maintenance of the basal activity of rat HPA axis acting through ETA and ETB receptor subtypes, which are partially insensitive to BQ-123 and BQ-788. Conversely, the involvement of ETs in the modulation of the HPA axis responses to various stresses is very doubtful.
Malendowicz
L K
LK
Department of Histology and Embryology, School of Medicine, Poznan, Poland.
Nussdorfer
G G
GG
Meneghelli
V
V
Nowak
M
M
Markowska
A
A
Majchrzak
M
M
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects; D000450:Aldosterone / Q000097:blood; D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects; D003345:Corticosterone / Q000097:blood; D019332:Endothelin-1 / Q000494:pharmacology*; D004986:Ether / Q000494:pharmacology; D005260:Female; D006801:Humans; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*
D019332:Endothelin-1; D004986:Ether; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone