Clinical pharmacological studies on the interaction between alpha-adrenoceptors and calcium antagonists

On the basis of animal studies, it has been proposed that calcium antagonists selectively interfere with the pressor response to alpha 2-adrenoceptor antagonists and have less direct action on alpha 1-adrenoceptor mechanisms. In placebo-controlled randomized studies in healthy normotensives, we have found that verapamil 160 mg significantly increases the fall in blood pressure after prazosin 1 mg orally. In part, this appears to be related to the cardioinhibitory and negative chronotropic action of verapamil, but it is also likely to depend on increases in bioavailability of prazosin and higher plasma levels when the drug is given with verapamil. Interactions of calcium antagonists with alpha-receptors were further explored in a study in which the pressor responses to intravenous angiotensin II were compared with those after phenylephrine (alpha 1-agonist) or alpha-methylnoradrenaline (alpha 2-agonist) in subjects treated with verapamil or nisoldipine, a new dihydropyridine related to nifedipine. Both calcium antagonists attenuated the pressor response to all three pressor substances to a similar degree. There was no evidence that pressor responses to alpha-methylnoradrenaline were selectively or more extensively reduced. Calcium antagonists can modify responses to both alpha 1- and alpha 2-receptors. Calcium antagonists in combination with drugs modifying adrenoceptor activity may have useful additional antihypertensive activity.