Abstract
The aims of this study were to ascertain the mechanism(s) of relaxant action of exogenous superoxide dismutase (SOD) in aortic rings obtained from 12-week, streptozotocin(STZ)-diabetic and age-matched control rats, and to examine the effects of alpha-lipoic acid (ALA) treatment (for 6 weeks, after 6 weeks of untreated diabetes) on SOD-induced relaxations. Thoracic aorta rings were suspended to isolated tissue chamber, and the changes in isometric tension were recorded. SOD produced a greater relaxation in untreated-diabetic rings compared with control rings. ALA treatment partially reversed SOD-induced relaxation in diabetic aorta. Pretreatment of rings with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microm) inhibited SOD-induced relaxation. This effect of L-NAME was markedly observed in control and ALA-treated-diabetic rings compared with untreated-diabetic rings. SOD-induced relaxation was also inhibited by catalase (60 U/ml) in untreated-diabetic rings but not in ALA-treated-diabetic and control rings. Pretreatment with the cyclooxygenase inhibitor, indomethacin, or the catalase inhibitor, aminotriazole, had no effect on SOD-induced relaxation in any ring. Findings suggested that: (i) in normal physiological conditions, the relaxant effect of SOD is related to the inhibition of superoxide anion radicals (*O(2)(-))-induced endothelium-derived relaxing factor/nitric oxide (EDRF/NO) destruction in the rat aorta; (ii) in diabetic state, excess *O(2)(-) increasingly inhibits basal EDRF/NO, and the dismutation of excess *O(2)(-) to H(2)O(2) is enhanced by exogenous SOD. H(2)O(2) a vasorelaxant molecule, which probably accounts for the increased responsiveness of diabetic rings to exogenous SOD; and (iii) the reversal effect of in vivo ALA treatment on SOD-induced relaxation in diabetic aorta is probably linked with the elimination of *O(2)(-)/H(2)O(2), which mediates the recovery of basal EDRF/NO availability.
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