Influence of calcium-entry blockade on vasoconstrictor responses in feline mesenteric vascular bed.

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The subtypes of postjunctional alpha-adrenoceptors activated by neuronally released and exogenous norepinephrine and the source of calcium used for vasoconstrictor responses were investigated in the feline mesenteric vascular bed. Under constant flow conditions, intra-arterial injections of phenylephrine and UK14304, alpha 1- and alpha 2-adrenoceptor agonists, increased mesenteric arterial perfusion pressure in a dose-related manner. Prazosin, an alpha 1-antagonist, reduced vasoconstrictor responses to phenylephrine without altering responses to UK14304. Yohimbine, an alpha 2-antagonist, reduced responses to UK14304 without altering responses to phenylephrine. The same pattern of blockade was observed in animals pretreated with 6-hydroxydopamine to destroy the integrity of adrenergic terminals. Responses to phenylephrine and UK14304 were reduced by nitrendipine, a calcium-entry blocking agent, and this agent decreased vasoconstrictor responses to sympathetic nerve stimulation, tyramine, and norepinephrine. Responses to sympathetic nerve stimulation were selectively blocked by prazosin, but responses to norepinephrine were selectively blocked by yohimbine. Vasoconstrictor responses to tyramine were reduced by both prazosin and yohimbine. Nitrendipine also reduced responses to angiotensin II, U46619, a prostaglandin endoperoxide analogue, Bay K 8644, and potassium chloride. These data suggest the presence of alpha 1- and postjunctional alpha 2-adrenoceptors and support the hypothesis that norepinephrine released by nerve excitation acts mainly on alpha 1-receptors but that exogenous norepinephrine acts primarily on alpha 2-receptors. However, norepinephrine released by tyramine acts on both receptor subtypes. Nitrendipine inhibited responses to the alpha 1- and alpha 2-adrenoceptor agonists as well as those to nerve released and exogenous norepinephrine, the calcium agonist, Bay K 8644, and to other vasoconstrictor agents. These data suggest that in the feline mesenteric vascular bed, an extracellular source of calcium ions is required for vasoconstriction induced by a variety of mechanisms including activation of alpha 1- and postjunctional alpha 2-adrenoceptors.