JP: Effects of cocaine on excitation-contraction coupling of aortic smooth muscle from the ferret

The mechanism by which cocaine alters vascular tone is not fully understood. We determined the effects of cocaine on exci-tation-contraction coupling of isolated ferret aorta. Cocaine in concentrations < 10-4 M caused a contractile response in a dose-dependent manner. The response of control muscle was significantly larger than that in muscle from ferrets pretreated with reserpine. Cocaine-induced contraction was not affected by endothelial factors, but was significantly inhibited by prazo-sin 10-7M pretreatment. The intracellular calcium ([Ca"],), as measured with aequorin, rose in conjunction with cocaine-in-duced contraction. The degree of contraction generated by 10-4 M cocaine decreased after higher concentrations of cocaine 2 10- M, while aequorin luminescence remained elevated above the levels before 10-6M cocaine. The dose-response re-lationships of norepinephrine and sympathetic nerve stimula-tion were enhanced by 10- M cocaine in control muscles; this did not occur in muscles from reserpine pretreated ferrets. In conclusion, (a) cocaine in concentrations 10-4M caused vas-cular contraction presumably by its presynaptic action with consequent alpha-i adrenoceptor activation and consequent ICa++I, rise; (b) high concentrations of cocaine 2 10-3 M re-duced muscle tone by decreasing the Ca++ sensitivity of the contractile proteins; and (c) supersensitivity to norepinephrine was mediated by cocaine's action on adrenergic nerve endings