Nitric oxide acutely modulates hypothalamic and neurohypophyseal carbon monoxide and hydrogen sulphide production to control vasopressin, oxytocin and atrial natriuretic peptide release in rats

摘要

Nitric oxide (NO) negatively modulates the secretion of vasopressin (AVP), oxytocin ( OT ) and atrial natriuretic peptide ( ANP ) induced by the increase in extracellular osmolality, whereas carbon monoxide ( CO) and hydrogen sulphide (H 2 S) act to potentiate it; however, little information is available for the osmotic challenge model about whether and how such gaseous systems modulate each other. 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?μmol?L ‐1 sodium nitroprusside ), CO (100?μmol?L ‐1 tricarbonylchloro[glycinato]ruthenium [II]) and H 2 S (10?mmol?L ‐1 sodium sulphide) donors and nitric oxide synthase ( NOS) (300?μmol?L ‐1 N ω ‐methyl‐ l ‐arginine [LNMMA]), haeme oxygenase (HO) (200?μmol?L ‐1 Zn(II) deuteroporphyrin IX 2,4‐bis‐ethylene glycol [ZnDPBG]) and cystathionine β‐synthase ( CBS ) (100?μmol?L ‐1 aminooxyacetate [AOA]) inhibitors on the release of hypothalamic ANP and hypothalamic and neurohypophyseal AVP and OT , as well as on the activities of NOS , HO and CBS . L NMMA reversed hyperosmolality‐induced NOS activity, and enhanced hormonal release by the hypothalamus and neurohypophysis, in addition to increasing CBS and hypothalamic HO activity. AOA decreased hypothalamic and neurohypophyseal CBS activity and hormonal release, whereas Zn DPBG inhibited HO activity and hypothalamic hormone release; however, in both cases, AOA did not modulate NOS and HO activity and Zn DPBG did not affect NOS and CBS activity. Thus, our data indicate that, although endogenous CO and H 2 S positively modulate AVP , OT and ANP release, only NO plays a concomitant role of modulator of hormonal release and CBS activity in the hypothalamus and neurohypophysis and that of HO activity in the hypothalamus during an acute osmotic stimulus, which suggests that NO is a key gaseous controller of the neuroendocrine system.