title: Reactive oxygen species are physiological mediators of the noradrenergic signaling pathway in the mouse supraoptic nucleus.
abstract: Free radicals are essential for the vasopressin (AVP) response to plasmatic hyperosmolarity. Noradrenergic afferents are the major projections on the supraoptic nucleus (SON) of the hypothalamus and stimulate the expression of AVP via a nitric oxide (NO) pathway. In this study, we investigated the mechanisms linking free radicals and noradrenaline (NA)-induced regulation of AVP. Analysis of Tg8 transgenic mice, invalidated for the monoamine oxidase-A gene and with consequently high levels of brain monoamines and AVP in the SON, showed that free radicals are more abundant in their SON than in that of wild-type mice (WT). Antioxidant superoxide dismutase 1 and 2 and catalase enzyme activities were also higher in these mice than in WT. This may explain the observed absence of cytotoxicity that would otherwise be associated with such high level of free radicals. Treatment of Tg8 mice with α-MPT, a blocking agent for NA synthesis, decreased both the production of free radicals and the AVP levels in the SON. Furthermore, incubation of ex vivo slices including the SON with NA increased the production of free radicals and AVP levels in wild-type mice. When NA was associated with α-lipoic acid, an antioxidant blocking the production of free radicals, AVP remained at its control level, indicating that free radicals are required for the effect of NA on the expression of AVP. In slices incubated with SNP, a producer of NO, free radicals and AVP levels increased. When NA was associated with L-NAME (a NO synthase blocker), the levels of free radicals and AVP were the same as in controls. Thus, the noradrenaline-NO pathway, which stimulates the expression of vasopressin, involves free radicals. This study provides further evidence of the physiological importance of free radicals, which should no longer be considered solely as cytotoxic factors.
authors.affiliation: UPMC Université Paris 06, F-75005 Paris, France; INSERM, UMRS 1130, F-75005 Paris, France; CNRS, UMR 8246, F-75005 Paris, France.
authors.forename: Ronald
authors.initials: R
authors.lastname: St-Louis
authors.affiliation: UPMC Université Paris 06, F-75005 Paris, France; INSERM, UMRS 1130, F-75005 Paris, France; CNRS, UMR 8246, F-75005 Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Parmentier
authors.affiliation: UPMC Université Paris 06, F-75005 Paris, France; INSERM, UMRS 1130, F-75005 Paris, France; CNRS, UMR 8246, F-75005 Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Grange-Messent
authors.affiliation: UPMC Université Paris 06, F-75005 Paris, France; INSERM, UMRS 1130, F-75005 Paris, France; CNRS, UMR 8246, F-75005 Paris, France.
authors.forename: Sakina
authors.initials: S
authors.lastname: Mhaouty-Kodja
authors.affiliation: UPMC Université Paris 06, F-75005 Paris, France; INSERM, UMRS 1130, F-75005 Paris, France; CNRS, UMR 8246, F-75005 Paris, France. Electronic address: helene.pouzet@snv.jussieu.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Hardin-Pouzet
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D005609:Free Radicals / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000378:metabolism*; D008063:Thioctic Acid / Q000494:pharmacology; D046509:Tissue Culture Techniques; D014667:Vasopressins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
chemical_list: D002374:Catalase; D005609:Free Radicals; D008781:Methyltyrosines; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D009599:Nitroprusside; D009638:Norepinephrine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D008063:Thioctic Acid; D014667:Vasopressins; D000099156:Superoxide Dismutase 2; C000606291:Sod1 protein, mouse
keywords: Free radicals; Nitric oxide; Noradrenaline; Supraoptic nucleus; Vasopressin