Koçak G, Karasu C
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
Diabetes Obes Metab. 2002 Jan;4(1):69-74. doi: 10.1046/j.1463-1326.2002.00174.x.
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.
本研究旨在确定外源性超氧化物歧化酶（SOD）对12周龄链脲佐菌素（STZ）诱导的糖尿病大鼠及年龄匹配的对照大鼠主动脉环的舒张作用机制，并研究α-硫辛酸（ALA）治疗（糖尿病未经治疗6周后进行6周治疗）对SOD诱导舒张的影响。
将胸主动脉环悬挂于离体组织浴槽中，记录等长张力的变化。
与对照环相比，SOD在未经治疗的糖尿病环中产生更大的舒张作用。ALA治疗部分逆转了糖尿病主动脉中SOD诱导的舒张。用N（G）-硝基-L-精氨酸甲酯（L-NAME，100 μmol）预处理环可抑制SOD诱导的舒张。与未经治疗的糖尿病环相比，在对照环和ALA治疗的糖尿病环中明显观察到L-NAME的这种作用。在未经治疗的糖尿病环中，过氧化氢酶（60 U/ml）也可抑制SOD诱导的舒张，但在ALA治疗的糖尿病环和对照环中则无此作用。用环氧合酶抑制剂吲哚美辛或过氧化氢酶抑制剂氨基三唑预处理对任何环中SOD诱导的舒张均无影响。
研究结果表明：（i）在正常生理条件下SOD的舒张作用与抑制超氧阴离子自由基（O₂⁻）诱导的大鼠主动脉中内皮源性舒张因子/一氧化氮（EDRF/NO）破坏有关；（ii）在糖尿病状态下，过量的O₂⁻越来越多地抑制基础EDRF/NO，外源性SOD可增强过量O₂⁻向H₂O₂的歧化。H₂O₂是一种血管舒张分子，这可能解释了糖尿病环对外源性SOD反应性增加的原因；（iii）体内ALA治疗对糖尿病主动脉中SOD诱导舒张的逆转作用可能与O₂⁻/H₂O₂的消除有关，这介导了基础EDRF/NO可用性的恢复。
