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


METHODS
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.


RESULTS
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.


CONCLUSIONS
The results of this study add further insights to our armamentarium against cerebral vasospasm.
Gazi University, Neurosurgery Department, Ankara, Turkey. alpob@yahoo.com
Fikret
F
Dogulu
Sureyya
S
Barun
Hakan
H
Emmez
Cigdem
C
Elmas
Baran
B
Onal
Hayrunnisa Bolay
HB
Belen
Deniz
D
Erdogan
Erhan
E
Ilgit
Yusuf
Y
Sarioglu
Gokhan
G
Kurt
Sevim
S
Ercan
M Kemal
MK
Baykaner
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000648:ultrastructure; D002533:Cerebral Angiography; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D019332:Endothelin-1 / Q000633:toxicity; D005260:Female; D008297:Male; D046529:Microscopy, Electron, Transmission; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D009579:Nitrobenzoates / Q000494:pharmacology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy*
D020533:Angiogenesis Inhibitors; D018118:Chloride Channels; D019332:Endothelin-1; D009579:Nitrobenzoates; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid