GABA-induced vasorelaxation mediated by nitric oxide and GABAA receptor in non diabetic and streptozotocin-induced diabetic rat vessels.

Diabetes has profound, negative effects on the function of arteries and arterioles. Hypertension is considered an independent risk factor for cardiovascular mortality in diabetic patients. The present study was designed to determine whether GABA-induced vasorelaxation in normal and streptozotocin-induced diabetic rat vessels is mediated by nitric oxide and the GABAA receptor. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). Eight weeks later, superior mesenteric arteries of all groups were isolated and perfused according to the McGregor method. Baseline perfusion pressure of STZ diabetic rats was significantly higher than non-diabetic rats in both intact and denuded endothelium. In the presence of bicuculline, a selective GABAA receptor blocker, GABA-induced relaxation in intact and denuded endothelium mesenteric beds of non-diabetic and STZ diabetic rats was suppressed. But in the presence of L-NAME, a nitric oxide synthesis inhibitor, although GABA- induced vasorelaxation was not suppressed at a dose of 1 µM of GABA in all groups, this response was suppressed with the other doses of GABA. From the results of this study it may be concluded that the vasorelaxatory effect of GABA is mediated by the GABAA receptor and nitric oxide in both STZ diabetic and non-diabetic vessels.