Peroxynitrite versus nitric oxide in early diabetes.

Abstract Background Peroxynitrite is a toxic compound formed during the inactivation of nitric oxide (NO) by the superoxide anion. The physiologic significance of this pathway of NO metabolism has never been documented in vivo. Because peroxynitrite provides a pathway for the inactivation of NO we postulated that peroxynitrite's correlation with physiologic parameters would be the opposite of those associated with NO, which is a vasodilator and suppresses sudomotor function. We assessed the significance of peroxynitrite by comparing its associations with blood pressure (BP) and sudomotor responses with those of NO. Methods Thirty-seven patients with type 1 diabetes enrolled in a longitudinal study of oxidative stress. Nitric oxide was assessed from nitrite and nitrate (collectively NOx) and peroxynitrite was assessed from the nitrotyrosine (nTy) content of protein. Results nTy was 13.3 ± 2.0 μmol/L in the control subjects and 26.8 ± 4.4 μmol/L, 26.1 ± 4.3 μmol/L, and 32.7 ± 4.3 μmol/L in the diabetic patients ( P v 75.5 ± 1.7 at the third evaluation, P P P P P P Conclusions The conversion of NO oxide to peroxynitrite is physiologically significant in humans.