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

Kensuke Egashira, Kathleen G. Morgan, James P. Morgan

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    44 Citations (Scopus)

    Abstract

    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 ≤ 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 ≥ 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 ≥ 10-4 M caused vascular contraction presumably by its presynaptic action with consequent alpha-1 adrenoceptor activation and consequent [Ca++]| rise; (b) high concentrations of cocaine 2: 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.

    Original languageEnglish
    Pages (from-to)1322-1328
    Number of pages7
    JournalJournal of Clinical Investigation
    Volume87
    Issue number4
    DOIs
    Publication statusPublished - Apr 1991

    All Science Journal Classification (ASJC) codes

    • Medicine(all)

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