Investigations into interactions between doxazosin and enalaprilat at alpha 1-adrenoceptors in anaesthetized rats.
1. In anaesthetized intact Sprague-Dawley rats, the angiotensin-converting enzyme inhibitor enalaprilat, 1 mg/kg, had no significant effect on the pressor responses to the alpha 1-adrenoceptor agonist phenylephrine (PE). Doxazosin 1 mg kg was found to be a potent alpha 1-adrenoceptor antagonist. 2. The combination of enalaprilat 1 mg/kg plus doxazosin 1 mg/kg was 3.3-fold more potent in antagonizing alpha 1-adrenoceptors than doxazosin 1 mg/kg alone. 3. After treatment of rats with deoxycorticosterone acetate (DOCA) twice weekly for 5 weeks, the alpha 1-adrenoceptor antagonist action of doxazosin in anaesthetized rats was not potentiated by enalaprilat 1 mg/kg. 4. Since DOCA treatment suppresses renin activity, these findings strongly support the hypothesis that angiotensin II can modulate the functional activity of alpha 1-adrenoceptor in vascular smooth muscle.
Hypertension Unit, Clinical Pharmacology Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
J
J
Marwood
G
G
Tierney
G
G
Stokes
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology; D017292:Doxazosin; D004347:Drug Interactions; D004357:Drug Synergism; D015773:Enalaprilat / Q000494:pharmacology*; D005260:Female; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D000804:Angiotensin II; D010656:Phenylephrine; D003900:Desoxycorticosterone; D015773:Enalaprilat; D017292:Doxazosin; D011224:Prazosin