An in vitro study of interactions between doxazosin and enalaprilat at vascular alpha 1-adrenoceptors.
1. Isolated perfused male Sprague-Dawley rat tail artery segments were used to investigate interactions between the alpha-1-adrenoceptor antagonist, doxazosin, and the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, using phenylephrine (PE) as the alpha 1-adrenoceptor agonist. 2. In concentrations of up to 10(-5) mol/L, enalaprilat had no effect on arterial responses to PE. 3. Doxazosin produced a concentration-dependent competitive alpha 1-adrenoceptor antagonism, yielding a mean pA2 value of 8.72. 4. In the continuous presence of 10(-6) mol/L enalaprilat, doxazosin with a pA2 value of 9.10 was a 2.4-fold more potent alpha 1-adrenoceptor antagonist than in the absence of enalaprilat. 5. These results are interpreted to indicate that endogenously produced angiotensin II can modulate the activity of alpha 1-adrenoceptors in vascular smooth muscle.
Tierney
G
G
Clinical Pharmacology Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Marwood
J
J
Stokes
G
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D017292:Doxazosin; D004347:Drug Interactions; D004656:Enalapril / Q000031:analogs & derivatives* / Q000494:pharmacology; D015773:Enalaprilat; D066298:In Vitro Techniques; 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*; D012084:Renin-Angiotensin System / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D004656:Enalapril; D015773:Enalaprilat; D017292:Doxazosin; D011224:Prazosin