Effect of a chloride channel inhibitor, 5-nitro-2- (3-phenylpropylamino)-benzoate, on endothelin-1 induced vasoconstriction in rabbit basilar artery

Endothelin-1 (ET-1) has been implicated in the pathophysiology of cerebral vasospasm. Chloride (Cl-) channels exist in vascular smooth muscle and activation of these channels leads to depolarization and contraction. The aim of the present study was to test the effect of 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), a Cl- channel antagonist, on the ET-1-induced cerebral vasospasm in rabbit basilar artery and thus investigate the contribution of Cl- channels. Thirty rabbits were divided into five groups and received intra-arterial injection of isotonic saline (Group I, n=6), ET-1 (group II, n=6), ET-1 plus NPPB (Group III, n=6), dimethylsulfate (DMSO4) (Group IV, n = 6) and NPPB (Group V, n=6). Pre and post injection basilar artery diameters were measured in each group and transmission electron microscopic investigations on basilar arteries were performed. The mean pre-injection and post-injection vessel diameters were 0.8833 mm and 0.7000 mm in ET-1 group, 0.6833 mm and 0.8500 mm in ET-1 + NPPB group. NPPB administered prior to ET-1 injection, prevented the ET-1-induced vasoconstriction. Additionally, NPPB prevents the ET-1 induced changes in vessel wall and neurons in the brain stem. The results of this study add further insights to our armamentarium against cerebral vasospasm.