Inhibition of oxidative radical production prevents diabetes‐induced vascular dysfunction through decreased arginase activation

Elevated arginase (ARG) activity and expression are associated with various cardiovascular diseases. Our lab previously reported that the oxidative species ONOO − and H 2 O 2 increase arginase activity/expression in bovine aortic endothelial cells (BAEC). Further, a NADPH oxidase (NOX) inhibitor, apocynin attenuated the effect of H 2 O 2 on arginase activity. We hypothesized that inhibiting the production of oxidative radicals in diabetes would prevent vascular endothelial dysfunction by reducing ARG activity/expression. To test this concept, we used bovine aortic endothelial cells (BAEC) treated with high glucose or normal glucose media and aortic tissue from normoglycemic and diabetic wild type (WT) and NOX 2 knockout (KO) mice. ARG activity was increased in high‐glucose treated BAEC (51%) as well as in aorta from WT‐D mice (82%). Both were prevented by 18 hr incubation with ONOO − decomposition catalyst FeTPPS or apocynin. Aorta from WT diabetic mice exhibited marked reduction of maximum endothelium‐dependent relaxation to acetylcholine (48%) compared to WT mice (62%). Vasorelaxation in the NOX 2 KO diabetic mice was comparable with that in NOX 2 KO normoglycemic mice. In conclusion, reduction in the levels of NOX‐derived oxidative radicals prevents diabetes‐induced elevation of arginase activity and preserves endothelium dependent vasorelaxation. (Support NIH HL70215, NIH EY11766)