Cameron N E, Cotter M A
Department of Biomedical Sciences, University of Aberdeen, UK.
Diabetologia. 1992 Nov;35(11):1011-9. doi: 10.1007/BF02221675.
The effects of 3 months streptozotocin-induced diabetes mellitus on contraction and relaxation of aorta were examined in vitro. A further diabetic group was treated with a novel sulphonylnitromethane-based aldose reductase inhibitor for 3 months following diabetes induction. Diabetes resulted in reduced maximal tension production, particularly for responses to phenylephrine (p < 0.001) and serotonin (p < 0.001). However, with aldose reductase inhibitor treatment, responses were in the non-diabetic range. The ratio of maximum contractions to noradrenaline and phenylephrine were 28% elevated by diabetes (p < 0.01), which may suggest increased alpha 2-adrenoreceptor-mediated responses. Endothelium-independent relaxation to glyceryl trinitrate was unaffected by diabetes or treatment. By contrast, there were 38% deficits in endothelium-dependent relaxation to acetylcholine (p < 0.001) and Ca2+ ionophore A23187 (p < 0.001) with diabetes which were prevented by aldose reductase inhibitor treatment (p < 0.001). A 121% shift in the concentration giving a 50% maximum effect for acetylcholine towards lower sensitivity with diabetes (p < 0.001) was also largely corrected by treatment (p < 0.001). A non-diabetic group treated with aldose reductase inhibitor showed a 30% decrease in the 50% effective concentration for acetylcholine (p < 0.05). A 15% deficit in maximum relaxation to the ATP-sensitive K+ channel opener cromakalim for the diabetic group (p < 0.001) was prevented by aldose reductase inhibitor treatment (p < 0.01). We conclude that there are polyol pathway related abnormalities for contraction, some aspects of endothelium-independent relaxation, but particularly for endothelium-dependent relaxation in aorta from chronic streptozotocin-diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
在体外研究了链脲佐菌素诱导的3个月糖尿病对主动脉收缩和舒张的影响。另一糖尿病组在诱导糖尿病后用一种新型的基于磺酰基硝基甲烷的醛糖还原酶抑制剂治疗3个月。糖尿病导致最大张力产生降低，尤其是对去氧肾上腺素（p<0.001）和5-羟色胺（p<0.001）的反应。然而，经醛糖还原酶抑制剂治疗后，反应处于非糖尿病范围内。糖尿病使去甲肾上腺素和去氧肾上腺素的最大收缩比率升高了28%（p<0.01），这可能表明α2-肾上腺素能受体介导的反应增加。糖尿病或治疗对硝酸甘油的非内皮依赖性舒张无影响。相比之下，糖尿病使乙酰胆碱（p<0.001）和Ca2+离子载体A23187（p<0.001）的内皮依赖性舒张出现38%的缺陷，而醛糖还原酶抑制剂治疗可预防这些缺陷（p<0.001）。糖尿病使乙酰胆碱产生50%最大效应的浓度向较低敏感性方向偏移121%（p<0.001），治疗也在很大程度上纠正了这一偏移（p<0.001）。用醛糖还原酶抑制剂治疗的非糖尿病组，乙酰胆碱的50%有效浓度降低了30%（p<0.05）。糖尿病组对ATP敏感性钾通道开放剂卡巴胆碱的最大舒张出现15%的缺陷（p<0.001），醛糖还原酶抑制剂治疗可预防此缺陷（p<0.01）。我们得出结论，在慢性链脲佐菌素诱导糖尿病大鼠的主动脉中，存在与多元醇途径相关的收缩异常、非内皮依赖性舒张的某些方面异常，但尤其是内皮依赖性舒张异常。（摘要截短至250字）
