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.
Dogulu
Fikret
F
Gazi University, Neurosurgery Department, Ankara, Turkey. alpob@yahoo.com
Barun
Sureyya
S
Emmez
Hakan
H
Elmas
Cigdem
C
Onal
Baran
B
Belen
Hayrunnisa Bolay
HB
Erdogan
Deniz
D
Ilgit
Erhan
E
Sarioglu
Yusuf
Y
Kurt
Gokhan
G
Ercan
Sevim
S
Baykaner
M Kemal
MK
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