Studies on the interactions between the angiotensin converting enzyme inhibitor enalaprilat and calcium antagonists in rats

OBJECTIVETo investigate the hypotheses that the synergistic hypotensive interaction between angiotensin converting enzyme (ACE) inhibitors and calcium antagonists is mediated via α1-adrenoceptor blockade and that in the presence of ACE inhibitors the α1-adrenoceptor potency of clinically used calcium antagonists may be sufficiently enhanced to add to the hypotensive effect. METHODSThe interactions between the ACE inhibitor enalaprilat and the calcium antagonists diltiazem, cinnarizine, felodipine and verapamil were studied in anesthetized rats for effects on blood pressure and in isolated perfused rat tail arteries for effects at α1-adrenoceptors. RESULTSIt was found that in isolated tail arteries enalaprilat had no effect on the weak α1-adrenoceptor antagonist actions of diltiazem, cinnarizine and felodipine. Similarly, enalaprilat did not affect the hypotensive responses to these calcium antagonists. However, enalaprilat was found to potentiate the α1-adrenoceptor antagonist action of verapamil, both in vitro and in vivo, as well as the hypotensive action of verapamil. CONCLUSIONSThese results support the above hypothesis in the case of verapamil only; for calcium antagonists in general the hypothesis was not supported. The results are consistent with a growing body of evidence showing that the distinction between calcium antagonists and α1-adrenoceptor antagonists is becoming less sharply defined.