Nitric oxide modulation of the hypothalamo-neurohypophyseal system

Abstract

Nitric oxide (NO), a free radical gas produced endogenously from the amino acid L-arginine by NO synthase (NOS), has important functions in modulating vasopressin and oxytocin secretion from the hypothalamo-neurohypophyseal system. NO production is stimulated during increased functional activity of magnocellular neurons, in parallel with plastic changes of the supraoptic nucleus (SON) and paraventricular nucleus. Electrophysiological data recorded from the SON of hypothalamic slices indicate that NO inhibits firing of phasic and non-phasic neurons, while L-NAME, an NOS inhibitor, increases their activity. Results from measurement of neurohypophyseal hormones are more variable. Overall, however, it appears that NO, tonically produced in the forebrain, inhibits vasopressin and oxytocin secretion during normovolemic, isosmotic conditions. During osmotic stimulation, dehydration, hypovolemia and hemorrhage, as well as high plasma levels of angiotensin II, NO inhibition of vasopressin neurons is removed, while that of oxytocin neurons is enhanced. This produces a preferential release of vasopressin over oxytocin important for correction of fluid imbalance. During late pregnancy and throughout lactation, fluid homeostasis is altered and expression of NOS in the SON is down-and up-regulated, respectively, in parallel with plastic changes of the magnocellular system. NO inhibition of magnocellular neurons involves GABA and prostaglandin synthesis and the signal-transduction mechanism is independent of the cGMP-pathway. Plasma hormone levels are unaffected by icv 1H-[1, 2, 4]oxadiazolo-[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor) or 8-Br-cGMP administered to conscious rats. Moreover, cGMP does not increase in homogenates of the neural lobe and in microdialysates of the SON when NO synthesis is enhanced during osmotic stimulation. Among alternative signal-transduction pathways, nitrosylation of target proteins affecting activity of ion channels is considered.

Nitric oxide modulation of ETB receptor-induced vasopressin release by rat and mouse hypothalamo-neurohypophyseal explants

“…At the beginning of the test period, IRL 1620 (N-succinyl-[Glu 9 ,Ala 11,15 ]-endothelin-1 fragment 8-21; Sigma RBI), a selective ETB receptor agonist, was added to the hypothalamic side of the barrier. Concentration of IRL 1620 ranged from 0.1 pM to 10 nM.…”

“…Recent studies indicate that nitric oxide generated by neural-astroglial sources modifies ET signaling within the central nervous system (19,27,42). Immunohistochemical and in situ hybridization studies have demonstrated nitric oxide synthase (NOS), citrulline, and NADPH-diaphorase activity within the hypothalamo-neurohypophyseal system (HNS; 11,39,42). Osmotic or hypovolemic stimuli that increase activity of magnocellular neurons are associated with enhanced NADPH-diaphorase activity in this region (21,32).…”

“…In contrast, the firing rates of the AVP neurons increase after injection of a NOS inhibitor (18), consistent with a tonic inhibitory nitrergic influence on AVP release. Results from in vivo studies are more variable depending upon the use and type of anesthetic, the hydration state of the animal, or whether the nitric oxide donor or NOS inhibitor was injected intravenously or into the cerebral ventricles (11). Notably, pharmacological inhibition of NOS is frequently associated with a concurrent increase in arterial pressure that may suppress AVP release via baroreflex mechanisms, thereby masking an effect by nitric oxide (27,29).…”

Dp71 gene disruption alters the composition of the dystrophin-associated protein complex and neuronal nitric oxide synthase expression in the hypothalamic supraoptic and paraventricular nuclei

“…b-DG, a1-Syn, and utrophins) in the SON and the PVN of the Dp71-null hypothalamus. We also analyzed nNOS expression, because this protein potentially interacts with the DAPC and because it represents an index of osmoregulatory axis activation (Kadekaro 2004). Indeed, in the hypothalamoneurohypophysis complex, NO is an important modulator of vasopressin synthesis and secretion (Yuan et al 2006, Raison et al 2011, St-Louis et al 2012.…”

“…Indeed, in the hypothalamoneurohypophysis complex, NO is an important modulator of vasopressin synthesis and secretion (Yuan et al 2006, Raison et al 2011, St-Louis et al 2012. nNOS and NADPH diaphorase, the histochemical marker of NOS activity, are both present in magnocellular neurons (Grange-Messent et al 2004, Kadekaro 2004, Maolood et al 2007. Their expression levels and activity increase when magnocellular neuron activity increases in response to osmotic stimulation, dehydration, or hypovolemia (Kadowaki et al 1994, Villar et al 1994, Ueta et al 1995.…”