Pharmacological Research, Vol. 38, No. 1, 1998 Article Number: fr980332 ( ) THE EFFECT OF SUCCINIC ACID MONOMETHYL ESTER SAM ON THE RESPONSES OF ISOLATED THORACIC AORTA IN STREPTOZOTOCIN-DIABETIC RATS ¨ a b b b c S. OZYAZGAN , V. SENSES , E. INCE , G. SULTUYBEK , T. UTKAN and A.G.  AKKAN a, a Department of Pharmacology, Cerrahpasa Faculty of Medicine, Uni ersity of Istanbul, 34303 Istanbul, Turkey, b GETAM, Cerrahpasa Faculty of Medicine, Uni ersity of Istanbul, 34303 Istanbul, Turkey and c Department of Pharmacology, Faculty of Medicine, Uni ersity of Kocaeli, Kocaeli, Turkey Accepted 1 April 1998 Ž . 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 Ž . Ž. SAM has the vascular effect in thoracic aorta of streptozotocin STZ -diabetic rats. 1 Ž . Body weights of diabetic rats were significantly increased after SAM treatment P  0.05 . Ž. 2 Ten-day SAM treatment did not significantly affect blood glucose levels in SAM-treated Ž. control and SAM-treated STZ-diabetic rats. 3 Maximum tension responses to nora- Ž 1 . drenaline and KCl 80 mmol l were not significantly different among all the experimen- Ž. Ž . tal groups. 4 pD log EC values for noradrenaline of untreated diabetic rats were 2 50 significantly less than those of controls, SAM-treated control and SAM-treated diabetic rats Ž . P  0.01, P  0.001 and P  0.05, respectively . SAM treatment normalized the decreased Ž. sensitivity of noradrenaline response in diabetic rats. 5 Fast, slow and total components of Ž 5 1 . responses to noradrenaline 10 mol l  EC were not significantly different among 90 Ž. all the experimental groups. 6 There were no significant differences between aorta Ž precontracted with noradrenaline from controls and STZ-diabetic untreated and SAM- . treated rats in pD values and the potency of maximum relaxation to acetylcholine or in 2 pD values to sodium nitroprusside. In conclusion, 10-day SAM treatment increases the 2 sensitivity of diabetic  aortic rings to noradrenaline compared to untreated diabetic control rats.  1998 The Italian Pharmacological Society KEY WORDS: streptozotocin, succinic acid monomethyl ester, aorta, contraction. INTRODUCTION MacDonald et al. discovered that the methyl esters of succinic acid were new potent insulin secreta-   gogues 1  3 . Then, several reports confirmed the   insulinotropic action of these esters 4  9 . In addi- Ž . tion, the monomethyl ester of succinic acid SAM was recently found to protect pancreatic islet B-cells against the impairment of glucose-stimulated insulin release caused by either glucopenia or starvation   Ž . 10,11 and against streptozotocin STZ -induced di-   abetes mellitus 12 . Altered reactivity of vascular smooth muscle and impaired endothelium-dependent relaxation may be involved in the pathogenesis of diabetic vascular complications. Studies on vascular reactivity using  Corresponding author. the STZ-diabetic rat have reported inconsistent re- sults with increased, decreased and unchanged re- sponsiveness to noradrenaline, acetylcholine and   sodium nitroprussiate 13  17 . The present study was designed to define whether SAM has the vascular effect in the thoracic aorta of STZ-diabetic rats. MATERIALS AND METHODS Animals Adult male and female Wistar rats, weighing 200  300 g were used in this study. They received a standard pellet diet and had free access to tap water. Ž . The rats n  36 were divided into four groups: Ž . I. Control group n  11 ; Ž . II. SAM-treated control group n  9; 104366189807007307$30.000 1998 The Italian Pharmacological Society