Effects of peroxynitrite on the reactivity of diabetic rat aorta

Endogenous nitric oxide (NO) reacts with superoxide to form peroxynitrite, which is capable of either oxidizing or nitrating various biological substr ates. We compared the vasodilatory effect of exogenous peroxynitrite with t he effects of decomposed peroxynitrite or sodium nitrite in precontracted a orta isolated from streptozotocin-induced diabetic and age-matched control rats. Peroxynitrite (10 nmol/l to 300 mu mol/l) produced a concentration-de pendent relaxation in aortic rings with or without endothelium. Relaxation was also observed with a higher concentration of its decomposition product or sodium nitrite, although these relaxations were considerably slower and with reduced sensitivity. Endothelium-containing rings were less sensitive to the vasorelaxant effect of peroxynitrite than the endothelium-denuded ri ngs in control (pD(2) was 5.19 +/- 0.06 in rings with endothelium and 5.86 +/- 0.03 in rings without endothelium, p < 0.01) but not in diabetic aorta (pD(2) was 5.97 +/- 0.05 in rings with endothelium and 6.12 +/- 0.06 in rin gs without endothelium, p > 0.05). The maximum relaxation to peroxynitrite also increased in diabetics, but did not change by removal of the endotheli um either in diabetic or control rings. Diabetes did not alter the relaxati ons elicited by both decomposed peroxynitrite and sodium nitrite. Peroxynit rite-induced relaxation was not inhibited by diethylenetriaminepentaacetic acid, an inhibitor of hydroxyl radical formation. Pretreatment with peroxyn itrite (1 mu mol/l, 15 min) significantly suppressed the phenylephrine-indu ced tone and acetylcholine-stimulated endothelium-dependent relaxation, bot h effects were more pronounced in diabetic than in control aorta. The incre ased responsiveness of diabetic vessels to exogenous peroxynitrite seems to be related to depressed basal NO bioavailability and may be considered as a compensatory way against activated contractile mechanisms of diabetic vas cular smooth muscle. Copyright (C) 2001 S.Karger AG, Basel.