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Does enalaprilat modulate the alpha 1-adrenoceptor antagonism of doxazosin in isolated rat tail arteries?
Does enalaprilat modulate the alpha 1-adrenoceptor antagonism of doxazosin in isolated rat tail arteries?
Enalaprilat enhances the alpha 1-adrenoceptor antagonism of doxazosin in rat tail arteries, suggesting endogenous angiotensin II modulates vascular alpha 1-adrenoceptor activity.
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Should not change prescribing of doxazosin or ACE inhibitors; hypothesis-generating for angiotensin II modulation of vascular alpha1-adrenoceptors.
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.
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Tierney et al. (1989) studied this question.
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