STUDIES ON THE INTERACTIONS BETWEEN THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR ENALAPRILAT AND CALCIUM-ANTAGONISTS IN RATS

Objective To investigate the hypotheses that the synergistic hypotensi ve interaction between angiotensin converting enzyme (ACE) inhibitors and calcium antagonists is mediated via alpha(1)-adrenoceptor blockade and that in the presence of ACE inhibitors the cll-adrenoceptor poten cy of clinically used calcium antagonists may be sufficiently enhanced to add to the hypotensive effect. Methods The interactions between th e ACE inhibitor enalaprilat and the calcium antagonists diltiazem, cin narizine, felodipine and verapamil were studied in anesthetized rats f or effects on blood pressure and in isolated perfused rat tail arterie s for effects at al-adrenoceptors. Results It was found that in isolat ed tail arteries enalaprilat had no effect on the weak alpha(1)-adreno ceptor antagonist actions of diltiazem, cinnarizine and felodipine. Si milarly, enalaprilat did not affect the hypotensive responses to these calcium antagonists. However, enalaprilat was found to potentiate the alpha(1)-adrenoceptor antagonist action of verapamii, both in vitro a nd in vivo, as well as the hypotensive action of verapamil. Conclusion s These results support the above hypothesis in the case of verapamil only; for calcium antagonists in general the hypothesis was not suppor ted, The results are consistent with a growing body of evidence showin g that the distinction between calcium antagonists and alpha(1)-adreno ceptor antagonists is becoming less sharply defined.