Sodium nitrite decreases systemic arterial pressure mediated by xanthine oxidoreductase in the rat

Abstract

Recent studies show that nitrite is reduced to NO and elicits significant vasodilator activity, however, the mechanism responsible for the conversion of nitrite to NO is still uncertain. In the present study, the responses of sodium nitrite upon inhibition of xanthine oxidoreductase (XOR) and aldehyde reductase were investigated in the anesthetized rat. The iv injections of sodium nitrite (0.01 ‐ 0.1 mmol/kg) caused dose related decreases in systemic arterial pressure that were significant in control and in L‐NAME treated rats. The responses were slower in onset than responses to SNP, and the dose response curve of nitrite was 2 log units to the right as that of SNP. The decreases in systemic arterial pressure in response to sodium nitrite were significantly reduced by allopurinol and cyanamide (10 ‐ 25 mg/kg iv) but the inhibitory effects were not additive. Both allopurinol and cyanamide caused small decreases in systemic arterial pressure in response to SNP or the NO donor DEA/NO. The results demonstrate that sodium nitrite has similar efficacy as that of SNP and DEA/NO in decreasing systemic arterial pressure but is less potent by a factor of 30 ‐ 100 and support the hypothesis that the conversion of nitrite to NO in large part is mediated by XOR in the anesthetized rat.