Buffering action of endogenous nitric oxide on the adrenocortical secretagogue effect of endothelins in the rat.
The secretagogue effect of endothelins (ETs) on the rat adrenal cortex is mediated by the ETB receptor. ETB receptors are coupled with nitric oxide (NO) synthase (NOS), and NO is known to inhibit steroid-hormone secretion from adrenal cortex. We investigated whether ETB-mediated NO production interferes with the stimulatory action of ETs on rat adrenal cortex. The selective agonist of ETB receptor BQ-3020 concentration-dependently increased aldosterone secretion from dispersed zona glomerulosa (ZG) cells and corticosterone secretion from dispersed zona fasciculata-reticularis (ZF/R) cells, and the NOS inhibitor NG-nitro-L-arginine methylester (L-NAME) potentiated the effect of BQ-3020 in a concentration-dependent manner. The guanylate cyclase inhibitor Ly-83583, at a concentration suppressing guanylin- and L-arginine-induced cyclic-GMP release from dispersed adrenocortical cells, did not affect the secretory response of ZG and ZF/R cells to BQ-3020. ET-1, an agonist of both ETA and ETB receptors, stimulated the release of both aldosterone and corticosterone by in situ perfused rat adrenal gland. This effect was potentiated by L-NAME and unaffected by Ly-83583. Collectively, our findings allow us to suggest that endogenous NO exerts in vivo and in vitro a cyclic-GMP-independent buffering action on the ETB receptor-mediated adrenocortical secretagogue action of ETs.
Mazzocchi
G
G
Department of Human Anatomy and Physiology, Section of Anatomy, University of Padua, I-35121 Padua, Italy.
Neri
G
G
Malendowicz
L K
LK
Rebuffat
P
P
Nussdorfer
G G
GG
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D005768:Gastrointestinal Hormones; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D045265:Natriuretic Peptides; D009569:Nitric Oxide / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000634:Aminoquinolines; D019332:Endothelin-1; D016232:Endothelins; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010446:Peptide Fragments; D010455:Peptides; C072685:guanylin; C075771:BQ 3020; D009569:Nitric Oxide; D000450:Aldosterone; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester