AN IN VITRO STUDY OF INTERACTIONS BETWEEN DOXAZOSIN AND ENALAPRILAT AT VASCULAR α1-ADRENOCEPTORS

doi:10.1111/j.1440-1681.1989.tb01567.x

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Wiley InterScience

Clinical and Experimental Pharmacology and Physiology

Volume 16 Issue 4, Pages 329 - 332

Published Online: 28 Jun 2007

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AN IN VITRO STUDY OF INTERACTIONS BETWEEN DOXAZOSIN AND ENALAPRILAT AT VASCULAR α₁-ADRENOCEPTORS

Garth Tierney ¹ , John Marwood ¹ ^, ² Gordon Stokes ¹

¹ Hypertension Unit, Clinical Pharmacology Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia

Correspondence to ² Dr J. Marwood, Hypertension Unit, Clinical Pharmacology Department, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.

KEYWORDS

α₁-adrenoceptor • angiotensin converting enzyme • doxazosin • enalaprilat • rat tail artery

ABSTRACT

1. Isolated perfused male Sprague-Dawley rat tail artery segments were used to investigate interactions between the α-₁-adrenoceptor antagonist, doxazosin, and the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, using phenylephrine (PE) as the α₁-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 α₁-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 α₁-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 α₁-adrenoceptors in vascular smooth muscle.

Received 5 December 1988

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1440-1681.1989.tb01567.x About DOI