Jf. Marwood et al., A STUDY OF THE INTERACTION BETWEEN THE HYPOTENSIVE ACTIONS OF DOXAZOSIN AND ENALAPRILAT IN ANESTHETIZED RATS, Journal of hypertension, 10(3), 1992, pp. 265-270
Objective and design: This study was designed to test whether previous
work, which showed that the angiotensin converting enzyme (ACE) inhib
itor enalaprilat potentiated the alpha-1-adrenoceptor antagonist activ
ity of doxazosin in isolated rat tail arteries, could be extended to d
emonstrate a synergistic hypotensive effect of these two drugs. Method
s: Groups of untreated or chronically deoxycorticosterone acetate (DOC
A)-salt-treated female Sprague-Dawley rats were used. Rats were anaest
hetized with Inactin (barbiturate); drugs were administered via a jugu
lar venous catheter; blood pressure was monitored via a carotid arteri
al 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 DO
CA-salt (which suppresses renin and angiotensin II production): (1) th
ere was no synergism between the hypotensive actions of enalaprilat an
d doxazosin; (2) doxazosin was more potent than in untreated rats; and
(3) enalaprilat lowered blood pressure, suggesting a hypotensive mech
anism separate from ACE inhibition. Conclusion: In the absence of angi
otensin II (resulting from enalaprilat administration or from chronic
DOCA-salt), doxazosin had a greater hypotensive action than in the pre
sence of angiotensin II. This is consistent with the concept that angi
otensin II modulates alpha-1-adrenoceptor activity.