Local and neurally mediated effects of sufentanil on canine skeletal muscle vascular resistance

R. J. O'Keefe, L. Domalik-Wawrzynski, J. L. Guerrero, C. E. Rosow, E. Lowenstein, W. J. Powell

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9 Scopus citations

Abstract

The present study examines both the local and neurally mediated effects of sufentanil, a new synthetic opioid, on the vascular resistance of the isolated, separately perfused canine gracilis muscle. Infusions (50 μg/min) of sufentanil into the gracilis arteries of nine denervated gracilis muscles did not produce a direct vascular effect. Because morphine has been previously shown to produce a central sympatholytic effect, the neural effect of sufentanil was examined in 12 innervated muscles under conditions of either low or high background sympathetic activity produced by either hemorrhage or transfusion of the dog. After i.v. sufentanil (20 μg/kg), all dogs experienced a rapid parallel fall in gracilis vascular resistance (GVR) and mean arterial pressure. The GVR decreased under conditions of high and low sympathetic activity. With low sympathetic tone, the GVR decreased from a control value of 24.1 ± 4.4 S.E.M. to 6.6 ± 0.8 resistance units (RU), a value below the subsequently denervated level (13.2 ± 2.5 RU) (P < .05). In hemorrhaged animals with elevated control sympathetic tone, resistance declined from 38.4 ± 9.1 to 26.1 ± 4.4 RU (P <.05) but did not reach the denervated level (12.4 ± 2.7 RU). Local intra-arterial pharmacologic blockade of the gracilis muscle was performed in animals with low sympathetic tone. Intra-arterial atropine did not effect the neurogenic vasodilatory response to sufentanil, whereas prazosin abolished it. Intra-arterial H1 and H2 receptor blockade prevented the decline of GVR secondary to sufentanil below the denervated level. Thus, vasodilation associated with sufentanil administration is mediated solely through neurogenic mechanisms. These mechanisms include a passive withdrawal of alpha adrenergic activity and an active histaminergic mechanism.

Original languageEnglish
Pages (from-to)699-706
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume242
Issue number2
StatePublished - Dec 1 1987
Externally publishedYes

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    O'Keefe, R. J., Domalik-Wawrzynski, L., Guerrero, J. L., Rosow, C. E., Lowenstein, E., & Powell, W. J. (1987). Local and neurally mediated effects of sufentanil on canine skeletal muscle vascular resistance. Journal of Pharmacology and Experimental Therapeutics, 242(2), 699-706.