Cocaine constriction of rat basilar artery in situ: roles of nitric oxide and endothelin-1.
This study investigated whether cocaine constriction of rat basilar artery in situ is mediated by nitric oxide (NO) inhibition and/or endothelin (ET)-1 release. Cocaine (3-100 µmol/l) concentration-dependently constricted the basilar artery to a maximum of 18%. Nω-nitro-L-arginine (100 µmol/l) was without effect on constriction to 3 and 10 µmol/l cocaine. PD145065 (1 and 10 µmol/l), an ETA/B receptor antagonist, variably and at most partially inhibited the 100 µmol/l cocaine constriction. Capsaicin denervation of sensory nerves innervating the basilar, which contain ET-1 and NO synthase, also failed to influence cocaine constriction. These findings suggest that cocaine constriction of cerebral vessels (1) varies with respect to the involvement of ET-1 release and (2) unlike findings in the peripheral vasculature, the constriction is not mediated by inhibition of NO.
Research Service, Veterans Affairs Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
SeongHun
S
Yoon
Mario
M
Zuccarello
Robert M
RM
Rapoport
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D019332:Endothelin-1; D009842:Oligopeptides; C082887:PD 145065; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D003042:Cocaine; D002211:Capsaicin