Blockade of nitric oxide synthesis stimulates the activity of adrenal cortex

Abstract

Objective. Although it is known that nitric oxide modulates the activity of hypothalamic-pituitary-adrenal axis, its functional significance has not been elucidated. Additionally, there is no information on the effect of nitric oxide on cortical expression of glucocorticoid receptor. The purpose of this study was to investigate the influence of endogenous nitric oxide on structure and function of rat adrenal cortex and adrenocortical expression of glucocorticoid receptor. Methods. Adult female Wistar rats showing diestrus day 1 were treated with Nω-nitro-L-arginine-methyl ester (LNAME), an inhibitor of all three isoforms of nitric oxide synthase, at a dose of 30 mg/kg, subcutaneously. The concentrations of adrenocorticotropic hormone (ACTH) and corticosterone were determined by radioimmunoassay. Stereological and immunohistochemical analyses were performed on paraffin sections. Results. Blockade of nitric oxide production significantly increased blood levels of ACTH and corticosterone. Stereological analysis showed that treatment with L-NAME significantly decreased numerical density of the cells in all cortical zones. Consistent with the decreased numerical density, L-NAME significantly increased the volume of cells in cortical zones. Inhibition of nitric oxide synthesis decreased expression of glucocorticoid receptor in zona fasciculata and zona reticularis. Conclusion. Obtained results indicate that endogenous nitric oxide inhibits activity of adrenal cortex and modulates expression of glucocorticoid receptor.

Cilj. Iako je poznato da azot-monoksid moduliše aktivnost hipotalamo-hipofizno-nadbubrežne osovine, funkcionalni značaj tog delovanja nije rasvetljen. Pored toga, dejstvo azot-monoksida na kortikalnu ekspresiju glukokortikoidnog receptora nije istraženo. Cilj ovog rada bio je da se ispita uticaj endogenog azot-monoksida na strukturu i funkciju kore nadbubrežne žlezde pacova i adrenokortikalnu ekspresiju glukokortikoidnog receptora. Metode. Odrasle ženke pacova Wistar soja u metestrusnoj fazi ciklusa tretirane su Nω-nitro-L-arginin metil esterom (L-NAME), inhibitorom sve tri izoforme azotmonoksid sintaze, u dozi 30 mg/kg, subkutano. Koncentracije adrenokortikotropnog hormona (ACTH) i kortikosterona u krvi određene su radioimunološkom metodom. Na parafinskim presecima nadbubrežne žlezde izvršena je stereološka i imunohistohemijska analiza korteksa. Rezultati. Blokada sinteze azot-monoksida značajno povećava koncentracije ACTH i kortikosterona u krvi. Stereološka analiza je pokazala da tretman sa L-NAME značajno smanjuje numeričku gustinu ćelija u svim kortikalnim zonama. U skladu sa smanjenom numeričkom gustinom, L-NAME značajno povećava volumen ćelija u sve tri zone korteksa. Inhibicija sinteze azot-monoksida smanjuje ekspresiju glukokortikoidnog receptora u zoni fascikulati i zoni retikularis. Zaključak. Dobijeni rezultati ukazuju na mogućnost da endogeni azot-monoksid inhibiše aktivnost kore nadbubrežne žlezde i da moduliše ekspresiju glukokortikoidnog receptora.