Effects of cocaine on human and goat isolated cerebral arteries.
Cocaine abuse has been increasingly associated with cerebrovascular disease. We have studied the vasoactive properties of cocaine in branches of human middle cerebral artery and in goat middle cerebral artery isolated in an organ bath for isometric tension recording. Cocaine (10(-5) - 3 x 10(-4) M) induced small contractions, while higher concentrations (10(-3) - 3 x 10(-3) M) induced relaxation of human arteries at resting tension. In human arteries precontracted with KCl (50 mM), prostaglandin F- (10(-5) M) or endothelin-1(10(-9) M), cocaine (10(-6) - 3 x 10(-3) M) induced concentration-dependent relaxations which differed in terms of EC50 or maximum effect (Emax). With regard to goat arteries, cocaine (10(-6) - 3 x 10(-3) M) induced almost negligible changes in resting tension, and induced concentration-dependent relaxations of the arterial tone induced with KCl (50 mM). By contrast, goat arteries precontracted with prostaglandin F2 alpha (10(-5) M) or endothelin-1 (10(-9) M) showed biphasic concentration-response curves with concentration-dependent contractions to cocaine (10(-5) - 10(-3) M) and relaxation to the highest concentration (3 x 10(-3) M). Preincubation with cocaine (10(-4) - 10(-3) M) inhibited the contractile responses to CaCl2 (10(-6) - 10(-2) M) in depolarizing, Ca(2+)-free medium, and this inhibition was reversed by preincubation with the Ca2+ entry activator Bay K8644 (10(-10) - 10(-8) M). Therefore, cocaine induces tension changes in cerebral arteries which depend on the species, the arterial tone and the contractile agent inducing it. The relaxant effects could be attributed to the interference of cocaine with the role of Ca2+ in the maintenance of arterial tone, at least in part by blocking Ca2+ entry through membrane channels.
Salom
J B
JB
Centro de Investigación, Hospital Universitario La Fe, Valencia, Spain.
Torregrosa
G
G
Barberá
M D
MD
Jover
T
T
Ortí
M
M
Alborch
E
E
D000328:Adult; D000368:Aged; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D006041:Goats; D006801:Humans; D008297:Male; D008875:Middle Aged; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D015220:Calcium Channels; D003042:Cocaine