EFFECTS OF COCAINE ON HUMAN AND GOAT ISOLATED CEREBRAL-ARTERIES

Cocaine abuse has been increasingly associated with cerebrovascular di sease. We have studied the vasoactive properties of cocaine in branche s of human middle cerebral artery and in goat middle cerebral artery i solated in an organ bath for isometric tension recording. Cocaine (10( -5) - 3 x 10(-4) M) induced small contractions, while higher concentra tions (10(-3) - 3 x 10(-3) M) induced relaxation of human arteries at resting tension. In human arteries precontracted with KCl (50 mM), pro staglandin F-2 alpha (10(-5) M) or endothelin - 1 (10(-9) M), cocaine (10(-6) - 3 x 10(-3) M) induced concentration-dependent relaxations wh ich differed in terms of EC(50) or maximum effect (E(max)). With regar d to goat arteries, cocaine (10(-6) - 3 x 10(-3) M) induced almost neg ligible changes in resting tension, and induced concentration-dependen t relaxations of the arterial tone induced with KCl (50 mM). By contra st, goat arteries precontracted with prostaglandin F-2 alpha (10(-5) M ) or endothelin-1 (10(-9) M) showed biphasic concentration-response cu rves with concentration-dependent contractions to cocaine (10(-5) - 10 (-3) M) and relaxation to the highest concentration (3 x 10(-3) M). Pr eincubation with cocaine (10(-4) - 10(-3) M) inhibited the contractile responses to CaCl2 (10(-6) - 10(-2) M) in depolarizing, Ca2+-free med ium, and this inhibition was reversed by preincubation with the Ca2+ e ntry activator Bay K8644 (10(-10) - 10(-8) M). Therefore, cocaine indu ces 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 ro le of Ca2+ in the maintenance of arterial tone, at least in part by bl ocking Ca2+ entry through membrane channels.