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EFFECT OF ANGIOTENSIN II RECEPTOR BLOCKADE ON THE INTERACTION BETWEEN ENALAPRILAT AND DOXAZOSIN IN RAT TAIL ARTERIES
Author(s) -
Marwood John F.
Publication year - 1998
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1998.tb02245.x
Subject(s) - doxazosin , losartan , endocrinology , medicine , enalaprilat , angiotensin ii , antagonist , competitive antagonist , angiotensin ii receptor type 1 , phenylephrine , chemistry , receptor antagonist , bradykinin , yohimbine , angiotensin converting enzyme , ace inhibitor , receptor , biology , blood pressure
SUMMARY 1. Previous work has shown that enalaprilat, an inhibitor of angiotensin‐converting enzyme (ACE), potentiated the actions of ai‐adrenoceptor antagonists; it was hypothesized that angiotensin II (Angll) modulated the activity of α 1 ‐adrenoceptors. This hypothesis was tested in Sprague‐Dawley rat isolated perfused tail arteries using the AT 1 receptor antagonist losartan and the AT 2 receptor antagonist PD123319. 2. Losartan had no oti‐adrenoceptor antagonist effects at concentrations below 1 μmol/L. Similarly, losartan (0.1 μmol/L) had no effect on the α 1 ‐adrenoceptor antagonist action of doxazosin (1,10 nmol/L) nor on the potentiation of doxazosin by enalaprilat (1μmol/L). 3. PD123319 (0.1 μmol/L) had no α 1 ‐adrenoceptor antagonist effect but altered the mode of action of the α 1 ‐adrenoceptor antagonist doxazosin: PD123319 changed doxazosin from a competitive to a non‐competitive antagonist, as evidenced by the reduced slope of the dose‐response curve for the α 1 ‐adrenoceptor agonist phenylephrine. 4. These results suggest that Angll can modulate α 1 ‐adrenoceptor function in rat tail arteries via an indirect action at AT 2 receptors. However, the present results do not rule out the involvement of bradykinin, endothelin or prostaglandin in the modulation of α 1 ‐adrenoceptor function by angiotensin II.