Inorganic nitrite attenuates Ang II‐mediated contraction of renal arterioles via xanthine oxidase‐dependent generation of nitric oxide

Abstract

Objective Inorganic nitrite is emerging as a substrate for nitric oxide (NO) synthase-independent in vivo generation of NO. Physiologial and therapeutical effects of nitrite have been demonstrated in renal and cardiovascular disease, but its influence on renal microvascular function is not known. Methods Effects of nitrite (10−5 M) on isotonic contractions to Ang II (10−12 to 10−6 M) and L-NAME (10−4 M) were measured in isolated and perfused renal afferent arterioles. Results Nitrite alone mediated a mild vasodilatation of arterioles (6±2%). Ang II constricted arterioles in a concentration-dependent manner with a maximum response of 40±2%, and simultaneous nitrite treatment reduced the maximal response (15±5%). L-NAME enhanced maximal Ang II-mediated contraction (56±4%), and nitrite attenuated the maximal response (25±2%). The attenuating effect of nitrite on Ang II+L-NAME-induced contractions were abolished by the NO scavenger cPTIO (66±2%), the guanylyl cyclase inhibitor ODQ (58±4%), as well as the xanthine oxidase inhibitor oxypurinol (63±3%). Conclusion Inorganic nitrite undergoes xanthine oxidase-mediated reduction to NO in the renal microcirculation, and hence modulates the contractile behavior. This novel function of nitrite may contribute to the reported effects in renal and cardiovascular health and disease.