The effect of calcium channel blockers on alpha 1- and alpha 2-adrenoceptor-mediated vascular responsiveness in man.

This study investigated the effects in normotensive males of the calcium channel blockers, verapamil and nisoldipine, on the pressor responses mediated via alpha-adrenergic and non-adrenergic mechanisms. After the first doses of each drug and after 4 days continued treatment both verapamil and nisoldipine significantly attenuated the responses to angiotensin II with three- to fivefold rightward shifts of the pressor dose-response curves. Rightward shifts of comparable magnitude were obtained for phenylephrine (selective alpha 1-agonist), but with alpha-methylnoradrenaline (preferential alpha 2-agonist) only nisoldipine caused a significant twofold rightward shift and only during continued treatment. This study demonstrated that peripheral vascular adrenergic responses mediated via both alpha 1- and alpha 2-adrenoceptors in man are affected by calcium channel blocking drugs. There was no evidence that this effect was specifically linked to the alpha 2-adrenoceptor. The functional antagonism of peripheral vasopressor mechanisms was not significantly different for verapamil and nisoldipine.