Interactions between enalaprilat and doxazosin at rat tail artery alpha 1-adrenoceptors.
Using paired isolated perfused rat tail artery segments, it was found that enalaprilat, an ACE inhibitor, augmented 1.6-fold the contractile responses to phenylephrine (PE), an alpha 1-adrenoceptor agonist. Similarly, enalaprilat potentiated 1.9-fold the alpha 1-adrenoceptor antagonist activity of doxazosin in paired rat tail artery segments. In rats treated with deoxycorticosterone acetate (DOCA) 20 mg/kg i.m. twice weekly for 5 weeks, plasma renin activity fell from a control value of 5.73 +/- 0.93 to 0.04 +/- 0.01 ng of AI/ml/h. The inhibition of circulating renin activity in these animals was associated with a loss of the potentiating effects of enalaprilat upon the alpha 1-adrenoceptor antagonist action of doxazosin. The results are interpreted as indicating that angiotensin II (AII) can modulate the functional activity of alpha 1-adrenoceptors in vascular smooth muscle.
Marwood
J
J
Clinical Pharmacology Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Tierney
G
G
Stokes
G
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017292:Doxazosin; D004347:Drug Interactions; D015773:Enalaprilat / Q000494:pharmacology*; D008297:Male; 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; D012083:Renin / Q000097:blood; D013623:Tail / Q000098:blood supply
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D003900:Desoxycorticosterone; D012083:Renin; D015773:Enalaprilat; D017292:Doxazosin; D011224:Prazosin