title: A study of the interaction between the hypotensive actions of doxazosin and enalaprilat in anaesthetized rats.
abstract: OBJECTIVE
  This study was designed to test whether previous work, which showed that the angiotensin converting enzyme (ACE) inhibitor enalaprilat potentiated the alpha 1-adrenoceptor antagonist activity of doxazosin in isolated rat tail arteries, could be extended to demonstrate a synergistic hypotensive effect of these two drugs.
  
  
  METHODS
  Groups of untreated or chronically deoxycorticosterone acetate (DOCA)-salt-treated female Sprague-Dawley rats were used. Rats were anaesthetized with Inactin (barbiturate); drugs were administered via a jugular venous catheter; blood pressure was monitored via a carotid arterial catheter.
  
  
  RESULTS
  In previously untreated rats, pretreatment with enalaprilat shifted the dose-response curve for the hypotensive effect of doxazosin to the left, indicating synergism. In rats dosed with DOCA-salt (which suppresses renin and angiotensin II production): (1) there was no synergism between the hypotensive actions of enalaprilat and doxazosin; (2) doxazosin was more potent than in untreated rats; and (3) enalaprilat lowered blood pressure, suggesting a hypotensive mechanism separate from ACE inhibition.
  
  
  CONCLUSIONS
  In the absence of angiotensin II (resulting from enalaprilat administration or from chronic DOCA-salt), doxazosin had a greater hypotensive action than in the presence of angiotensin II. This is consistent with the concept that angiotensin II modulates alpha 1-adrenoceptor activity.
authors.affiliation: Clinical Pharmacology Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
authors.forename: J F
authors.initials: JF
authors.lastname: Marwood
authors.forename: G
authors.initials: G
authors.lastname: Tierney
authors.forename: G S
authors.initials: GS
authors.lastname: Stokes
mesh_terms: D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D017292:Doxazosin; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D015773:Enalaprilat / Q000627:therapeutic use*; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D011224:Prazosin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013874:Thiopental / Q000031:analogs & derivatives
chemical_list: D000959:Antihypertensive Agents; C004316:thiobutabarbital; D003900:Desoxycorticosterone; D015773:Enalaprilat; D013874:Thiopental; D017292:Doxazosin; D011224:Prazosin