Cameron N E, Cotter M A
Department of Biomedical Sciences, University of Aberdeen, Marischal College, Scotland, UK.
Eur J Pharmacol. 1993 Oct 12;243(1):47-53. doi: 10.1016/0014-2999(93)90166-f.
Rats were fed for 10 days with a 40% galactose diet, in order to chronically stimulate the polyol pathway. Thoracic aorta contraction and relaxation were studied. Compared to controls, galactosaemia did not influence contractions to phenylephrine or serotonin. Acetylcholine produced concentration-dependent relaxation of aortic rectangles precontracted with phenylephrine; galactosaemia caused a 25% deficit in maximum relaxation to acetylcholine (P < 0.01) and a 168% increase in EC50. There was a similar 25% reduction in relaxation to 3 microM calcium ionophore A23187 (P < 0.05). By contrast, there were no significant differences in endothelium-independent relaxation to nitroglycerine or cromakalim. The abnormalities in endothelium-dependent relaxation were completely prevented by treating galactosaemic rats with the aldose reductase inhibitor, ponalrestat. Thus, the data demonstrate that elevated polyol pathway activity contributes to reduced endothelium production, release or the action of nitric oxide in experimental galactosaemia, and suggest that this mechanism could also contribute to the vascular defects seen in diabetes mellitus.
为了长期刺激多元醇途径，给大鼠喂食40%半乳糖饮食10天。研究了胸主动脉的收缩和舒张情况。与对照组相比，半乳糖血症对苯肾上腺素或5-羟色胺引起的收缩没有影响。乙酰胆碱使预先用苯肾上腺素预收缩的主动脉条产生浓度依赖性舒张；半乳糖血症导致对乙酰胆碱的最大舒张减少25%（P<0.01），半数有效浓度（EC50）增加168%。对3微摩尔钙离子载体A23187的舒张也有类似的25%的降低（P<0.05）。相比之下，对硝酸甘油或克罗卡林的非内皮依赖性舒张没有显著差异。用醛糖还原酶抑制剂泊那司他治疗半乳糖血症大鼠可完全预防内皮依赖性舒张异常。因此，数据表明，在实验性半乳糖血症中，多元醇途径活性升高导致内皮产生、释放一氧化氮或一氧化氮作用降低，并表明该机制也可能导致糖尿病中出现的血管缺陷。
