title: Vascular xanthine oxidoreductase contributes to the antihypertensive effects of sodium nitrite in L-NAME hypertension.
abstract: Nitrate and nitrite have emerged as an important novel source of nitric oxide (NO). We have previously demonstrated that sodium nitrite is an antihypertensive compound that exerts antioxidant effects in experimental hypertension. These unpredicted antioxidant effects of nitrite raised the question whether the beneficial effects found were caused by its conversion to NO or simply due to reversal of endothelial dysfunction as a consequence of its antioxidant effects. Here, we evaluated the antihypertensive effects of a daily dose of sodium nitrite for 4 weeks in L-NAME-induced hypertension in rats. We studied the effects of nitrite on markers of NO bioavailability, vascular oxidative stress, and expression of xanthine oxidoreductase. Moreover, we tested if xanthine oxidoreductase inhibition could attenuate the acute hypotensive effects of sodium nitrite in L-NAME hypertensive rats. We found that a single pharmacological dose of sodium nitrite exerts antihypertensive effects in L-NAME-induced hypertension. While the beneficial antihypertensive properties of nitrite were associated with increased levels of NO metabolites, hypertension increased vascular xanthine oxidoreductase expression by approximately 40%, with minor increases in vascular superoxide production. The inhibition of xanthine oxidoreductase by oxypurinol attenuated the acute hypotensive effects of nitrite. Taken together, our results show that nitrite exerts antihypertensive effects in L-NAME hypertensive rats and provide evidence that xanthine oxidoreductase plays an important role in this antihypertensive effect.
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Montenegro
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Pinheiro
authors.forename: Jefferson H
authors.initials: JH
authors.lastname: Amaral
authors.forename: Graziele C
authors.initials: GC
authors.lastname: Ferreira
authors.forename: Rafael L
authors.initials: RL
authors.lastname: Portella
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012977:Sodium Nitrite / Q000627:therapeutic use*; D014968:Xanthine Dehydrogenase / Q000096:biosynthesis*
chemical_list: D000959:Antihypertensive Agents; D014968:Xanthine Dehydrogenase; D012977:Sodium Nitrite; D019331:NG-Nitroarginine Methyl Ester