Antagonism by nifedipine of alpha-1 and alpha-2 adrenoceptor-mediated responses of human digital arteries.
This study examines the effects of calcium-entry blockade by nifedipine on alpha-1 and alpha-2 adrenoceptor-mediated contractile responses of the human isolated digital artery to exogenous agonists and sympathetic nerve stimulation. Spiral strips of digital artery were mounted for isometric tension recording in physiological salt solution. Contractile responses to TL-99 and to norepinephrine in the presence of prazosin were effectively antagonized by rauwolscine and are therefore presumably mediated by alpha-2 adrenoceptors. Responses to norepinephrine in the presence of rauwolscine were antagonized by prazosin and are therefore mediated predominantly by alpha-1 adrenoceptors. Responses to methoxamine were antagonized by prazosin and, to a lesser extent, by rauwolscine, suggesting that this agonist is also activating alpha-2 adrenoceptors. Nifedipine antagonism of contractile responses was assessed as the percentage of inhibition of the area under the agonist concentration-effect curve or nerve stimulation frequency-effect curve. Nifedipine (10(-9) to 10(-7) M) inhibited responses to TL-99 and methoxamine to similar extents. Nifedipine (10(-8) and 10(-7) M) also had similar effects on the alpha-1 and alpha-2 adrenoceptor-mediated responses (in the presence of rauwolscine and prazosin, respectively) to either exogenous norepinephrine or sympathetic nerve stimulation. At concentrations up to 10(-6) M, nifedipine failed to reduce the efflux of [3H]norepinephrine produced by sympathetic nerve stimulation at either 2 or 8 Hz. We conclude that the alpha-1 and alpha-2 adrenoceptor-mediated contractile responses of the human digital artery are dependent to similar extents on calcium entry through the slow calcium channels of the cell membrane.
D004558:Electric Stimulation; D005385:Fingers / Q000098:blood supply*; D006801:Humans; D066298:In Vitro Techniques; D008729:Methoxamine / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014316:Tritium; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D013764:Tetrahydronaphthalenes; D014316:Tritium; D015016:Yohimbine; C016893:2-(N,N-dimethylamino)-6,7-dihydroxytetralin; D008729:Methoxamine; D009543:Nifedipine; D009638:Norepinephrine; D011224:Prazosin