324 - Sodium Nitrate Attenuates the Acute Antihypertensive and Vascular Effects of Sodium Nitrite by Inhibiting Nitrite-Reductase Activity of Xanthine Oxidoreductse

Abstract

The antihypertensive effects of nitrite are at least in part attributable to tissue reduction of nitrite to nitric oxide (NO) by xanthine oxidoreductase (XOR). XOR also reduces nitrate to nitrite, however, at a much lower rate than it reduces nitrite to NO. Here, we examined whether nitrate decreases the formation of NO from nitrite by XOR, and therefore attenuates its antihypertensive and vascular effects. Methods Blood pressure effects were studied in rats receiving Nω-nitro-L- arginine methyl ester (L-NAME) 100 mg/Kg orally to increase the mean of arterial pressure (MAP). Forty min later, they received nitrate (40 µmol/kg) or vehicle. Then increasing doses of sodium nitrite were infused into the femoral vein. Invasive MAP was assessed in the femoral artery. Vascular reactivity studies: The vasorelaxant effects of sodium nitrite (0.3 nMto 10 mM concentrations) were examined in aortic rings pre-contracted with phenylephrine 10-7M in the presence or absence of sodium nitrate 300 µM. In addition, mesenteric arterial bed preparations infused continuously with phenylephrine (3 µM to 8 µM). Sodium nitrate 300 µM or vehicle was added to the perfusion liquid and a concentration-response curve to nitrite (0.1 µM to 1 mM) was constructed. Nitrite reductase activity was measured by injecting XOR 100 mU/ml into a purge vessel containing nitrite 1 mM, NADPH 1 mM and NADH 1 mM in the presence or absence of sodium nitrate 30 mM, and NO was detected by chemiluminescence. Results Pretreatment with sodium nitrate attenuated nitrite-induced decreases in MAP. Pre-incubation of aortic rings with nitrate shifted the concentration-response curve in response to sodium nitrite to the right and reduced the maximum response. Adding sodium nitrate to the solution perfusing the mesenteric bed attenuated the fall in perfusion pressure induced by nitrite. Nitrate decreased nitrite-induced NO formation by XOR in the purge vessel. Conclusion Our results show that nitrate attenuates the acute blood pressure responses to nitrite by mechanisms that involve reduced nitrite-derived NO formation by XOR.