NO acutely modulates hypothalamic and neurohypophyseal CO and H2S production to control AVP, OT and ANP release in rats

Abstract

NO negatively modulates the secretion of vasopressin (AVP), oxytocin (OT) and atrial natriuretic peptide (ANP) induced by the increase in extracellular osmolality, whereas CO and H₂S act potentiating it; however, little information about whether and how such gaseous systems modulate each other is available for the osmotic challenge model. Therefore, using an acute ex vivo model of hypothalamic and neurohypophyseal explants (obtained from male 6/7‐week‐old Wistar rats) under conditions of extracellular iso‐ and hypertonicity, we determined the effects of NO (600 μM SNP), CO (100 μM CORM3) and H₂S (10 mM Na₂S) donors and NOS (300 μM LNMMA), HO (200 μM ZnDPBG) and CBS (100 μM AOA) inhibitors on the release of hypothalamic ANP and hypothalamic and neurohypophyseal AVP and OT, and on the activities of nitric oxide synthase (NOS), heme oxygenase (HO) and cystathionine β‐synthase (CBS). LNMMA reversed hyperosmolality‐induced NOS activity, and enhanced hormonal release by the hypothalamus and neurohypophysis, besides increasing CBS and hypothalamic HO activity. AOA decreased hypothalamic and neurohypophyseal CBS activity and hormonal release; while, ZnDPBG inhibited HO activity and hypothalamic hormone release; however, in both cases, neither AOA modulated NOS and HO activity, nor ZnDPBG affected NOS and CBS activity. Thus, our data indicate that, although endogenous CO and H₂S positively modulate AVP, OT and ANP release, only NO plays, in fact, a concomitant role of modulator of hormonal release and CBS activity in the hypothalamus and neurohypophysis and HO activity in the hypothalamus during an acute osmotic stimulus, which suggests that NO is a key gaseous controller of the neuroendocrine system.

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