葡萄糖、胰岛素或醛糖还原酶抑制对链脲佐菌素诱导的糖尿病大鼠主动脉环对内皮素-1反应的影响。

Effects of glucose, insulin or aldose reductase inhibition on responses to endothelin-1 of aortic rings from streptozotocin-induced diabetic rats.

作者信息

Hodgson W C, King R G

机构信息

Department of Pharmacology, Monash University, Clayton, Victoria, Australia.

出版信息

Br J Pharmacol. 1992 Jul;106(3):644-9. doi: 10.1111/j.1476-5381.1992.tb14389.x.

DOI:10.1111/j.1476-5381.1992.tb14389.x

PMID:1504747

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1907582/

Abstract

This study investigated the constrictor responsiveness to endothelin-1 (ET-1, 0.1 nM-0.1 microM) of aortic rings (under 10 g resting tension in Krebs solution) from 2- and 6-week streptozotocin (STZ, 60 mg kg-1, i.v.)-induced diabetic rats and vehicle-treated control rats. 2. In aortae from 2- and 6-week STZ-treated rats, and their corresponding controls, removal of endothelium caused leftward shifts of ET-1 concentration-response curves without affecting maximum responses. 3. Maximum responses to ET-1 were reduced in aortae from both 2- and 6-week STZ-treated rats compared to those from control rats. Such reductions were still evident after removal of the endothelium. 4. Decreased responsiveness to ET-1 of aortae from 2-week STZ-treated rats was still evident after chronic treatment with the aldose reductase inhibitor epalrestat, but not after chronic insulin treatment or in aortae bathed in high glucose (30 mM) Krebs solution. 5. Decreased responsiveness to ET-1 of aortae from 6-week STZ-treated rats (compared with those from controls) was still evident after chronic epalrestat treatment and in high glucose Krebs solution. 6. These data suggest that the decreased responsiveness to ET-1 observed in aortae from 2- and 6-week STZ-induced diabetic rats is not due to abnormal activity of the polyol pathway. The altered responsiveness in aortae from 2-week diabetic rats (compared with those from control rats) may possibly be a manifestation of changes (adaptive or otherwise) which occur as a result of high glucose concentrations in vivo.However, in aortae from rats with diabetes of longer duration, other mechanisms may also play a role in the altered responsiveness, since it was no longer reversible by bathing in high glucose Krebs solution.

摘要

本研究调查了链脲佐菌素（STZ，60 mg/kg，静脉注射）诱导的2周和6周糖尿病大鼠以及溶剂处理的对照大鼠的主动脉环（在Krebs溶液中静息张力为10 g）对内皮素-1（ET-1，0.1 nM - 0.1 μM）的收缩反应性。2. 在2周和6周STZ处理大鼠及其相应对照的主动脉中，去除内皮导致ET-1浓度-反应曲线向左移位，而不影响最大反应。3. 与对照大鼠相比，2周和6周STZ处理大鼠的主动脉对ET-1的最大反应均降低。去除内皮后，这种降低仍然明显。4. 用醛糖还原酶抑制剂依帕司他长期治疗后，2周STZ处理大鼠主动脉对ET-1的反应性降低仍然明显，但长期胰岛素治疗后或在高葡萄糖（30 mM）Krebs溶液中孵育的主动脉中则不明显。5. 长期依帕司他治疗后以及在高葡萄糖Krebs溶液中，6周STZ处理大鼠主动脉对ET-1的反应性降低（与对照大鼠相比）仍然明显。6. 这些数据表明，在2周和6周STZ诱导的糖尿病大鼠主动脉中观察到的对ET-1反应性降低并非由于多元醇途径的异常活性。2周糖尿病大鼠主动脉中反应性的改变（与对照大鼠相比）可能是体内高葡萄糖浓度导致的变化（适应性或其他）的表现。然而，在病程较长的糖尿病大鼠主动脉中，其他机制也可能在反应性改变中起作用，因为在高葡萄糖Krebs溶液中孵育后其反应性不再可逆。