Hypotensive activity of calcium entry blockers in rats. Relationship with depression of alpha 2-adrenoceptor-mediated vasopressor responses.

The hypotensive activity of a series of calcium entry blockers and various other vasodilators was quantified in pentobarbitone-anesthetized rats. Hypotensive activity was correlated linearly with the potency of these vasoactive agents to depress alpha 2-adrenoceptor-induced pressor responses in pithed rats. However, vasodilatation as such also influenced alpha 2-adrenoceptor-mediated vasoconstrictor processes. For this reason, the depressive action of the vasodilating compounds on alpha 2-adrenoceptor-induced pressor effects was also determined during vasopressin infusion, which counteracted the vasodilatation induced by the vasoactive compounds. It was found that the hypotensive activity exerted by the calcium entry blockers was directly related with their inhibitory activity to depress alpha 2-pressor responses. This relationship was not observed for the other vasodilators. The results provide further evidence for the hypothesis that vasodilatation induced by calcium entry blockers is caused by the selective impairment of that part of the vascular tone which is maintained by vascular postjunctional alpha 2-adrenoceptors.