Unraveling the origin of the nitrite-mediated hypoxic vasodilation

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  • Interdisciplinary Nanoscience Center
  • Department of Biological Sciences, Zoophysiology

Circulating nitrite has recently emerged as an important physiological metabolite that contributes to increase vasodilation during tissue hypoxia. Using a wire myograph, we have investigated how the nitrite-dependent vasodilation in rat aortic rings is controlled by oxygen tension, norepinephrine concentration, soluble guanylate cyclase (the target for vasoactive nitric oxide) and known nitrite-reductase activities, including that of hemoglobin, xanthine oxidase, endothelial nitric oxide synthase and the bc1 complex of the mitochondria under hypoxia. We found that vasodilation followed overall first-order dependency on nitrite concentration, at high and low oxygen levels, and that it was induced by nitrite concentrations comparable to those found in vivo, when using low oxygenation and norepinephrine levels. The nitrite vasoactivity during hypoxia was abolished upon inhibition of soluble guanylate cyclase and was unaffected by removal of the endothelium, by the presence of hemoglobin and inositol hexaphosphate (that increases the fraction of deoxygenated heme) and by inhibition of xanthine oxidase and the mitochondrial bc1 complex. Our results indicate that under hypoxia physiological nitrite concentrations are sufficient to induce NO-mediated vasodilation independently of the nitrite reductase activities here investigated. These results further indicate that the vasoactive effect of nitrite is intrinsic to the vessel and may be due to S-nitrosothiols formed within the arterial smooth muscle.



Original languageEnglish
JournalComparative Biochemistry and Physioogy, Part A
Volume146
Issue4
Pages (from-to)S159
DOIs
Publication statusPublished - 2007
EventSeventh International Congress of Comparative Physiology and Biochemistry - Bahia, Brazil
Duration: 12 Aug 200716 Aug 2007

Conference

ConferenceSeventh International Congress of Comparative Physiology and Biochemistry
CountryBrazil
CityBahia
Period12/08/200716/08/2007

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