Noradrenaline up‐regulates the neuronal and the inducible nitric oxide synthase isoforms in magnocellular neurons of rat brain slices

Abstract

Nitric oxide (NO) and noradrenaline (NA) are suggested to be implicated in the regulation of neuropeptide secretion in the supraoptic nuclei (SON) and the paraventricular nuclei (PVN) of the hypothalamus. Our study demonstrates short-term interactions between NA and the activity and expression of NO synthase (NOS) in magnocellular neurons, by using an ex vivo model of hypothalamic slices. In the SON as well as in the PVN, total NOS activity exhibited a time-dependant increase after an incubation with NA. In the SON, this increase of total NOS activity was in part the consequence of stimulation of the iNOS activity. Coimmunodetections showed that cells expressing the inducible form of NOS were not astrocytes but magnocellular neurons. Steady-state levels of iNOS and nNOS mRNA were dramatically enhanced by NA, particularly in the SON. Consequently, we provide new evidence that iNOS could play an important role in multiple physiological functions, including extracellular fluid balance, lactation, and parturition.

Features of the inducible nitric oxide synthase expression in paraventricular and supraoptic nuclei of hypothalamus in different models of arterial hypertension

“…Furthermore, our results about the iNOS expression in magnocellular nuclei of hypothalamus are consistent with data about expression of iNOS both in magnocellular neurons and glial cells [24]. This substantiates our suggestion about the constitutive role of iNOS the central nervous system activity, in particular, of hypothalamus.…”

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

“…In wild-type mice, we confirmed previous reports of nNOS in the magnocellular neurons located in the dorsal part of the SON and in the lateral part of the PVN (Vacher et al 2003, Maolood et al 2007. nNOS expression was higher in the SON and PVN of Dp71-null mice, which is similar to what has been reported to occur in response to osmotic stimulation (Kadowaki et al 1994), hypovolemia (Ueta et al 1998), and noradrenalin treatment (Grange-Messent et al 2004, Maolood et al 2007. Similarly, NADPH-diaphorase staining was higher in both the SON and PVN of Dp71-null mice.…”

“…These functions are fine-tuned by magnocellular activity, and among the different modulatory pathways, the NO pathway is particularly important (Antunes-Rodrigues et al 2004, Grange-Messent et al 2004, Maolood et al 2007. nNOS is expressed at high levels in the SON and PVN (Sagar & Ferriero 1987, Pasqualotto et al 1991, Arévalo et al 1992, Vincent & Kimura 1992) and its expression is functionally regulated by osmotic stimulation ( Kadowaki et al 1994, Villar et al 1994, Ueta et al 1998.…”

“…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.…”

β-Amyloid-Stimulated Microglia Induce Neuron Death via Synergistic Stimulation of Tumor Necrosis Factor α and NMDA Receptors

“…Although neuronal iNOS immunoreactivity has been reported previously (Heneka et al, 2003;Grange-Messent et al, 2004;Rodrigo et al, 2004;Small et al, 2004), its expression is certainly well documented in glia as well (Xie et al, 2002;Dehmer et al, 2004;Iravani et al, 2004;Morale et al, 2004;Wang et al, 2004). To confirm that our iNOS-mediated death was occurring via neuronally generated nitric oxide, we performed immunohistochemistry to determine which cell types in our culture were expressing iNOS.…”