Relaxatory Effect of Gamma-Aminobutyric Acid (GABA) is Mediated by Same Pathway in Diabetic and Normal Rat Mesenteric Bed vessel


1 Department of Basic Sciences, Gonabad University of Medical Sciences, Gonabad, Iran

2 Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Physiology, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran


Diabetes related dysfunction of resistance vessels is associated with vascular occlusive diseases. Vasorelaxant agents may have a role in control of diabetic cardiovascular complications. Gamma aminobutyric acid (GABA) has demonstrated to cause vasorelaxation. The present study was designed to determine i) the vasorelaxatory effect of GABA on diabetic vessels and ii) the role of endothelium in GABAinduced vasorelaxation.
Materials and Methods
After Diabetes induction,. Mesenteric arteries of animals were perfused. Vascular beds were constrictedwith phenylephrine. GABA (1 to 50 μM) was added into the medium and perfusion pressure was then recorded.
In all groups of animals, relaxant response to GABA in mesenteric bed appeared. Although diabetes induction did not change mesenteric bed response to GABA, denuded vessels showed a reduced response to GABA both in control and diabetic animals.
GABA can induce endothelium dependent vasorelaxation in mesenteric vessels in normal and diabetic rats.


1. Ozcelikay AT, Tay A, Guner S, Tasyaran V, Yildizoglu-Ari N, Dincer UD, et al. Reversal effects of L-arginine treatment on blood pressure and vascular responsiveness of streptozotocin-diabetic rats. Pharmacol Res 2000; 41:201-209.
2. Gammelsaeter R, Froyland M, Aragon C, Danbolt NC, Fortin D, Storm-Mathisen J, et al. Glycine, GABA and their transporters in pancreatic islets of Langerhans: evidence for a paracrine transmitter interplay. J Cell Sci 2004; 117:3749-3758.
3. Gimeno M, Pallas M, Newman AH, Camarasa J, Escubedo E. The role of cyclic nucleotides in the action of peripheral-type benzodiazepine receptor ligands in rat aorta. Gen Pharmacol 1994; 25:1553-1561.
4. Holmgaard K, Aalkjaer C, Lambert JD, Hessellund A, Bek T. The relaxing effect of perivascular tissue on porcine retinal arterioles in vitro is mimicked by N-methyl-D-aspartate and is blocked by prostaglandin synthesis inhibition. Acta Ophthalmol 2008; 86:26-33.
5. Ozdem SS, Sadan G. Impairment of GABA-mediated contractions of rat isolated ileum by experimental diabetes. Pharmacology 1999; 59:165-170.
6. Soltani N, Keshavarz M, Sohanaki H, Zahedi Asl S, Dehpour AR. Relaxatory effect of magnesium on mesenteric vascular beds differs from normal and streptozotocin induced diabetic rats. Eur J Pharmacol 2005; 508:177-181.
7. McGregor DD. The Effect of sympathetic nerve stimulation of vasoconstrictor responses in perfused mesenteric blood vessels of the rat. J Physiol 1965; 177:21-30.
8. Wagner JA, Varga K, Jarai Z, Kunos G. Mesenteric vasodilation mediated by endothelial anandamide receptors. Hypertension 1999; 33: 429-434.
9. Briede J, Stivrina M, Stoldere D, Vigante B, Duburs G. Effect of cerebrocrast, a new long-acting compound on blood glucose and insulin levels in rats when administered before and after STZ-induced diabetes mellitus. Cell Biochem Funct 2007; 25:673-680.
10. Abe A, Kawasoe C, Kondo Y, Sato K. Enhancement of norepinephrine-induced transient contraction in aortic smooth muscle of diabetic mice. Acta Med Okayama 2003; 57:45-48.
11. Hadi HA, Suwaidi JA. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag 2007; 3:853-876.
12. Diederich D, Skopec J, Diederich A, Dai FX. Endothelial dysfunction in mesenteric resistance arteries of diabetic rats: role of free radicals. Am J Physiol 1994; 266:H1153-1161.
13. Touyz RM. Role of magnesium in the pathogenesis of hypertension. Mol Aspects Med 2003; 24:107-136.
14. Erdo S, Varga B, Horvath E. Effect of local GABA administration on rat ovarian blood flow, and on progesterone and estradiol secretion. Eur J Pharmacol 1985; 111:397-400.
15. Fergus A, Lee KS. GABAergic regulation of cerebral microvascular tone in the rat. J Cereb Blood Flow Metab 1997; 17:992-1003.