Kappagoda T, Jayakody L, Rajotte R, Thomson A B, Senaratne M P
Department of Medicine, University of Alberta, Edmonton.
Clin Invest Med. 1989 Jun;12(3):187-93.
Experiments were designed to investigate the phenomenon of endothelium-dependent relaxation (EDR) to acetylcholine in two animal models of insulin dependent diabetes mellitus. Thoracic aortas obtained from streptozotocin diabetic rats and genetically diabetic biobreeding rats (BB rats) were used in this study. Concentration-effect curves to acetylcholine were carried out on aortic rings under isometric tension. Following the induction of diabetes with streptozotocin, half of the animals were treated with daily intermediate acting insulin and the other half maintained without insulin for a period of 12 weeks before the experiment. The diabetic BB rats were also maintained on insulin. The EDR to acetylcholine was not impaired in the aortas of streptozotocin diabetic rats (insulin treated as well as untreated) compared to nondiabetic controls. The scanning electron microscopic (SEM) appearances of the aortic endothelium did not differ among the three groups of animals. However, the EDR to acetylcholine was found to be impaired in the aortas of diabetic BB rats. (Maximum relaxation: 25.3 +/- 5.0% of the contraction to norepinephrine compared to 52.2 +/- 5.3% in controls.) The SEM appearances of the aortic endothelium in the diabetic BB rats were found to be abnormal with edema and loss of definition of cell margins compared to nondiabetic controls. The differences in EDR to acetylcholine seen between the two animal models of diabetes may be related to the different aetiologies of diabetes in the animals.
实验旨在研究胰岛素依赖型糖尿病两种动物模型中对乙酰胆碱的内皮依赖性舒张(EDR)现象。本研究使用了从链脲佐菌素糖尿病大鼠和遗传性糖尿病生物繁殖大鼠(BB大鼠)获取的胸主动脉。在等长张力下对主动脉环进行乙酰胆碱浓度 - 效应曲线实验。用链脲佐菌素诱导糖尿病后,一半动物每日接受中效胰岛素治疗,另一半在实验前12周不使用胰岛素维持原状。糖尿病BB大鼠也持续使用胰岛素。与非糖尿病对照组相比,链脲佐菌素糖尿病大鼠(胰岛素治疗组和未治疗组)主动脉对乙酰胆碱的EDR未受损。三组动物主动脉内皮的扫描电子显微镜(SEM)外观无差异。然而,发现糖尿病BB大鼠主动脉对乙酰胆碱的EDR受损。(最大舒张:与对照组的52.2±5.3%相比,对去甲肾上腺素收缩的25.3±5.0%。)与非糖尿病对照组相比,糖尿病BB大鼠主动脉内皮的SEM外观异常,有水肿且细胞边缘清晰度丧失。两种糖尿病动物模型中对乙酰胆碱的EDR差异可能与动物糖尿病的不同病因有关。