Interference of calcium entry blockade in vivo with pressor responses to alpha-adrenergic stimulation: effects of two unrelated blockers on responses to both exogenous and endogenously released norepinephrine.

To the extent that calcium availability is the final common mediator of vasoconstrictor responses, calcium entry blockade might interfere with physiologic responses to adrenergic stimulation. To test this hypothesis, we studied the effects of calcium entry blockade on pressor responses to norepinephrine in pithed, normal Sprague-Dawley rats in two different ways: (1) by evaluating the effects on pressor responsiveness to exogenous norepinephrine during differential blockade of alpha 1-(prazosin, 0.3 mg/kg) and of alpha 2-receptors (yohimbine, 0.3 mg/kg) and (2) by comparing the effects of calcium entry blockade with those of prazosin and those of rauwolscine (a specific alpha 2-antagonist) on pressor responses to infusions of both endogenously released norepinephrine (electrical stimulation of the pithing rod) and exogenous norepinephrine. In the presence of alpha 1-blockade, both nitrendipine (0.01 mg/kg) and verapamil (0.6 mg/kg) shifted the norepinephrine pressor dose-response curve to the right but we...