Original Article Endothelial Nitric Oxide Synthase–Dependent Tyrosine Nitration of Prostacyclin Synthase in Diabetes In Vivo

There is evidence that reactive nitrogen species are impli-cated in diabetic vascular complications, but their sources and targets remain largely unidentified. In the present study, we aimed to study the roles of endothelial nitric oxide synthase (eNOS) in diabetes. Exposure of isolated bovine coronary arteries to high glucose (30 mmol/l D-glucose) but not to osmotic control mannitol (30 mmol/l) switched angiotensin II–stimulated prostacyclin (PGI2)-dependent relaxation into a persistent vasoconstriction that was sensitive to either indomethacin, a cyclooxygen-ase inhibitor, or SQ29548, a selective thromboxane recep-tor antagonist. In parallel, high glucose, but not mannitol, significantly increased superoxide and 3-nitrotyrosine in PGI2 synthase (PGIS). Concurrent administration of poly-ethylene-glycolated superoxide dismutase (SOD), L-ni