Studies on the interactions between the angiotensin converting enzyme inhibitor enalaprilat and calcium antagonists in rats.
OBJECTIVE
To investigate the hypotheses that the synergistic hypotensive interaction between angiotensin converting enzyme (ACE) inhibitors and calcium antagonists is mediated via alpha1-adrenoceptor blockade and that in the presence of ACE inhibitors the alpha1-adrenoceptor potency of clinically used calcium antagonists may be sufficiently enhanced to add to the hypotensive effect.


METHODS
The 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 alpha1-adrenoceptors.


RESULTS
It was found that in isolated tail arteries enalaprilat had no effect on the weak alpha1-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 alpha1-adrenoceptor antagonist action of verapamil, both in vitro and in vivo, as well as the hypotensive action of verapamil.


CONCLUSIONS
These 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 alpha1-adrenoceptor antagonists is becoming less sharply defined.
Marwood
J F
JF
Hypertension Unit, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002936:Cinnarizine / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D004110:Diltiazem / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015773:Enalaprilat / Q000008:administration & dosage*; D015736:Felodipine / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D005260:Female; D008297:Male; D023421:Models, Animal; D008955:Models, Cardiovascular; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000008:administration & dosage / Q000037:antagonists & inhibitors
D000317:Adrenergic alpha-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D002936:Cinnarizine; D014700:Verapamil; D004110:Diltiazem; D015773:Enalaprilat; D015736:Felodipine