Increased activity of H2O2 in aorta isolated from chronically streptozotocin-diabetic rats: Effects of antioxidant enzymes and enzyme inhibitors


Karasu Ç.

FREE RADICAL BIOLOGY AND MEDICINE, vol.27, no.1-2, pp.16-27, 1999 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 1-2
  • Publication Date: 1999
  • Doi Number: 10.1016/s0891-5849(99)00028-3
  • Title of Journal : FREE RADICAL BIOLOGY AND MEDICINE
  • Page Numbers: pp.16-27
  • Keywords: hydrogen peroxide, rat aorta, Streptozotocin-diabetes, oxidative stress, endothelium, nitric oxide, superoxide dismutase, free radicals, ENDOTHELIUM-DEPENDENT RELAXATION, SOLUBLE GUANYLATE-CYCLASE, ARTERIAL SMOOTH-MUSCLE, HYDROGEN-PEROXIDE, NITRIC-OXIDE, SUPEROXIDE-DISMUTASE, INSULIN-TREATMENT, VITAMIN-E, VASCULAR REACTIVITY, RELAXING FACTOR

Abstract

The effects of hydrogen peroxide (H2O2, 1 nM-5 mM) on the tone of the rings of aorta precontracted with phenylephrine (PE) were studied in 4-5 months streptozotocin (STZ)-diabetic rats and their age-matched controls. H2O2 induced brief contraction before relaxation in endothelium-containing rings that was more pronounced in diabetic rats. Removal of the endothelium or pretreatment of rings with N-G-nitro-L-arginine methyl ester (L-NAME, 100 mu M) abolished H2O2-induced immediate and transient increase in tone, but preincubation with indomethacin (10 mu M) had no effect on contractions induced by H2O2 in both group of animals. Pretreatment with L-NAME or indomethacin as well as absence of endothelium produced an inhibition of H2O2-induced relaxation that was more pronounced in diabetic rings. Chronically STZ-diabetes resulted in a significant increase in H2O2-induced maximum relaxation that was largely endothelium-dependent. Decreased sensitivity (pD(2)) of diabetic vessels to vasorelaxant action of H2O2 was normalized by superoxide dismutase (SOD, 80 U/ml). Pretreatment with SOD had no effect on H2O2-induced maximum relaxations in both group of animals but led to an increase in H2O2-induced contractions in control rats. When the rings pretreated with diethyldithiocarbamate (DETCA, 5 mM), H2O2 produced only contraction in control rats, and H2O2-induced relaxations were markedly depressed in diabetic rats. H2O2 did not affect the tone of intact or endothelium-denuded rings in the presence of catalase (2000 U/ml). Aminotriazole (AT, 10 mM) failed to affect H2O2-inciuced contractions or relaxations in all rings. Our observations suggest that increased production of oxygen-derived free radicals (OFRs) in diabetic state leads to a decrease in SOD activity resulting an increase in endogenous superoxide anions (O2(.-)), that is limited cytotoxic actions, and an increase in catalase activity resulting a decrease in both H2O2 concentrations and the production of harmful hydroxyl radical ((OH)-O-.) in diabetic aorta in long-term. present results indicate that increased vascular activity of H2O2 may be an important factor in the development of vascular disorders associated with chronically diabetes mellitus. Enhanced formation of (OH)-O-., that is a product of exogenous H2O2 and excess O-2(.-), seems to be contribute to increased relaxations to exogenously added H2O2 in chronically diabetic vessels. (C) 1999 Elsevier Science Inc.