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

Abstract

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-bisethylene 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. LNMMA 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 ZnDPBG inhibited HO activity and hypothalamic hormone release; however, in both cases, AOA did not modulate NOS and HO activity and ZnDPBG 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. K E Y W O R D S atrial natriuretic peptide, carbon monoxide, hydrogen sulphide, nitric oxide, oxytocin, vasopressin 2 of 16 | COLETTI ET aL. | INTRODUC TI ONThe release of vasopressin (AVP) and oxytocin (OT) by the hypothalamus and the neurohypophysis is a very complex and robust process that is controlled by many factors produced both within and outside these brain sites. 1 Among such factors, atrial natriuretic peptide (ANP) stands out as established modulator of thirst and AVP release, 2-4 whereas a novel class of small polar molecules, mainly represented by nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H 2 S), 5 have achieved prominence more recently.NO is produced from the amino acid l-arginine via a reaction catalysed by the enzyme nitric oxide synthase (NOS), which presents three major isoforms (neuronal [nNOS], endothelial [eNOS] and inducible [iNOS]), where, in the central nervous system (CNS), nNOS is considered the main isoform. 6 NOS active form is usually dimeric and exhibits an oxygenase domain, in which, in addition to ...

The Interaction of the Endogenous Hydrogen Sulfide and Oxytocin Systems in Fluid Regulation and the Cardiovascular System

“…CBS, OT and OTR displayed an opposite pattern of expression to CSE and were upregulated with injury. The differential regulation of these enzymes suggests a much more complex relationship between the OT and H 2 S systems in osmotic regulation than what was reported previously [ 4 , 24 ].…”

“…The authors concluded that H 2 S regulates the roles of both the behavioral and neuroendocrine responses to water deprivation independently of nitric oxide (NO) and stimulates OT secretion by inhibiting the NO system [ 4 ]. In a more recent study, in rat hypothalamic explants H 2 S was also shown to be a (positive) regulator of OT in response to acute osmotic stimulus, whereas NO played a key role as a negative neuroendocrine modulator of OT [ 24 ]. Additionally, Coletti et al localized constitutive expression of CBS in the rat hypothalamic SON and PVN, but an important omission in this model which may limit their findings was that they did not look for the interaction of CSE [ 24 ].…”

“…In a more recent study, in rat hypothalamic explants H 2 S was also shown to be a (positive) regulator of OT in response to acute osmotic stimulus, whereas NO played a key role as a negative neuroendocrine modulator of OT [ 24 ]. Additionally, Coletti et al localized constitutive expression of CBS in the rat hypothalamic SON and PVN, but an important omission in this model which may limit their findings was that they did not look for the interaction of CSE [ 24 ]. This omission assumes importance when considering the complex interaction of CSE and CBS, which were found to be expressed in an inverse fashion after cerebral injury [ 25 ].…”

“…This omission assumes importance when considering the complex interaction of CSE and CBS, which were found to be expressed in an inverse fashion after cerebral injury [ 25 ]. A further word of caution is warranted regarding the translational value of the above experiments [ 4 , 22 , 23 , 24 ]: they were all performed in rat models, and some of them on tissue explants. Ex vivo studies in general are a limited representation of the in vivo situation, and rats may not be the most appropriate model organism to study the effects of NO interactions, considering their much higher NO levels.…”

“…The role of OT in the heart has been recently reviewed [ 61 , 68 ], and interestingly enough OT shares many of the properties also reported for H 2 S, e.g., increase of glucose uptake in cardiac cells, anti-inflammatory and antioxidant activity [ 69 , 70 , 71 ], blood pressure lowering capacities via NO-mediated vasodilation [ 72 ], negative inotropic and chronotropic effects, natriuretic effects and effects on endothelial cell growth [ 14 , 68 , 73 , 74 ]. The NO-mediated vasodilatory effects of OT are also reported to regulate blood pressure [ 68 , 75 , 76 , 77 , 78 ] and body fluid homeostasis, albeit through an interaction with H 2 S [ 4 , 24 ].…”