Peroxynitrite (ONOO-), formed by the reaction between nitric oxide (·NO) and superoxide, has been implicated in the etiology of numerous disease processes. Low molecular weight antioxidants, including uric acid, may minimize ONOO--mediated damage to tissues. The tissue-sparing effects of uric acid are typically attributed to oxidant scavenging; however, little attention has been paid to the biology of the reaction products. In this study, a previously unidentified uric acid derivative was detected in NOO treated human plasma. The product of the uric acid/ONOO- reaction resulted in endothelium-independent vasorelaxation of rat thoracic aorta, with an ECho value in the range of 0.03-0.3 μM. Oxyhemoglobin, a ·NO scavenger, completely attenuated detectable ·NO release and vascular relaxation. Uric acid plus decomposed ONOO- neither released ·NO nor altered vascular reactivity. Electrochemical quantification of ·NO confirmed that the uric acid/ONOO- reaction resulted in spontaneous (thiol-independent) and protracted (t( 1/4 ) ~ 125 min) release of ·NO. Mass spectroscopic analysis indicated that the product was a nitrated uric acid derivative. The uric acid nitration/nitrosation product may play a pivotal role in human pathophysiology by releasing ·NO, which could decrease vascular tone, increase tissue blood flow, and thereby constitute a role for uric acid not previously described.
