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 excitation-contraction coupling of isolated ferret aorta. Cocaine in concentrations less than or equal to 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 prazosin 10(-7) M pretreatment. The intracellular calcium [( Ca++]i), as measured with aequorin, rose in conjunction with cocaine-induced contraction. The degree of contraction generated by 10(-4) M cocaine decreased after higher concentrations of cocaine greater than or equal to 10(-3) M, while aequorin luminescence remained elevated above the levels before 10(-6) M cocaine. The dose-response relationships of norepinephrine and sympathetic nerve stimulation were enhanced by 10(-6) M cocaine in control muscles; this did not occur in muscles from reserpine pretreated ferrets. In conclusion, (a) cocaine in concentrations less than or equal to 10(-4) M caused vascular contraction presumably by its presynaptic action with consequent alpha-1 adrenoceptor activation and consequent [Ca++]i rise; (b) high concentrations of cocaine greater than or equal to 10(-3) M reduced 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.
Egashira
K
K
Charles A. Dana Research Institute, Harvard-Thorndike Laboratory of Beth Israel Hospital, Boston, Massachusetts 02215.
Morgan
K G
KG
Morgan
J P
JP
D000320:Adrenergic Fibers / Q000187:drug effects*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005289:Ferrets; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology
D001285:Atropine; D012110:Reserpine; D003042:Cocaine; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin