Premium
Elimination of • O 2 − /H 2 O 2 by α‐lipoic acid mediates the recovery of basal EDRF/NO availability and the reversal of superoxide dismutase‐induced relaxation in diabetic rat aorta
Author(s) -
Koçak G.,
Karasu Ç.
Publication year - 2002
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1046/j.1463-1326.2002.00174.x
Subject(s) - superoxide dismutase , catalase , chemistry , streptozotocin , nitric oxide , aorta , lipoic acid , endocrinology , medicine , diabetes mellitus , enzyme , antioxidant , biochemistry , organic chemistry
Aim: 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 α‐lipoic acid (ALA) treatment (for 6 weeks, after 6 weeks of untreated diabetes) on SOD‐induced relaxations. Materials and Methods: Thoracic aorta rings were suspended to isolated tissue chamber, and the changes in isometric tension were recorded. Results: 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 µ m ) 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. Conclusion: 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.