Ozyazgan S, Senses V, Ince E, Sultuybek G, Utkan T, Akkan A G
Department of Pharmacology, Cerrahpasa Faculty of Medicine, University of Istanbul, Turkey.
Pharmacol Res. 1998 Jul;38(1):73-9. doi: 10.1006/phrs.1998.0332.
Succinic acid monomethyl ester (SAM) was recently proposed as an insulinotropic tool in non-insulin-dependent diabetes mellitus. The present study was designed to define whether SAM has the vascular effect in thoracic aorta of streptozotocin (STZ)-diabetic rats. (1) Body weights of diabetic rats were significantly increased after SAM treatment (P < 0.05). (2) Ten-day SAM treatment did not significantly affect blood glucose levels in SAM-treated control and SAM-treated STZ-diabetic rats. (3) Maximum tension responses to noradrenaline and KCl (80 mmol l-1) were not significantly different among all the experimental groups. (4) pD2 (-log EC50) values for noradrenaline of untreated diabetic rats were significantly less than those of controls, SAM-treated control and SAM-treated diabetic rats (P < 0.01, P < 0.001 and P < 0.05, respectively). SAM treatment normalized the decreased sensitivity of noradrenaline response in diabetic rats. (5) Fast, slow and total components of responses to noradrenaline (10(-5) mol l-1 approximately equal to EC90) were not significantly different among all the experimental groups. (6) There were no significant differences between aorta precontracted with noradrenaline from controls and STZ-diabetic (untreated and SAM-treated) rats in pD2 values and the potency of maximum relaxation to acetylcholine or in pD2 values to sodium nitroprusside. In conclusion, 10-day SAM treatment increases the sensitivity of diabetic-aortic rings to noradrenaline compared to untreated diabetic control rats.
琥珀酸单甲酯(SAM)最近被提议作为非胰岛素依赖型糖尿病的促胰岛素分泌工具。本研究旨在确定SAM对链脲佐菌素(STZ)诱导的糖尿病大鼠胸主动脉是否具有血管效应。(1)SAM治疗后糖尿病大鼠体重显著增加(P < 0.05)。(2)为期10天的SAM治疗对SAM处理的对照组和SAM处理的STZ糖尿病大鼠的血糖水平无显著影响。(3)所有实验组对去甲肾上腺素和KCl(80 mmol l-1)的最大张力反应无显著差异。(4)未治疗的糖尿病大鼠对去甲肾上腺素的pD2(-log EC50)值显著低于对照组、SAM处理的对照组和SAM处理的糖尿病大鼠(分别为P < 0.01、P < 0.001和P < 0.05)。SAM治疗使糖尿病大鼠对去甲肾上腺素反应的敏感性降低恢复正常。(5)所有实验组对去甲肾上腺素(10(-5) mol l-1 约等于EC90)反应的快速、慢速和总成分无显著差异。(6)用去甲肾上腺素预收缩的对照组和STZ糖尿病(未治疗和SAM治疗)大鼠主动脉在pD2值、对乙酰胆碱最大舒张效力或对硝普钠的pD2值方面无显著差异。总之,与未治疗的糖尿病对照大鼠相比,为期10天的SAM治疗增加了糖尿病主动脉环对去甲肾上腺素的敏感性。