A study of the interaction between the hypotensive actions of doxazosin and enalaprilat in anaesthetized rats.
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.
Marwood
J F
JF
Clinical Pharmacology Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Tierney
G
G
Stokes
G S
GS
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
D000959:Antihypertensive Agents; C004316:thiobutabarbital; D003900:Desoxycorticosterone; D015773:Enalaprilat; D013874:Thiopental; D017292:Doxazosin; D011224:Prazosin