Antagonist effect of losartan on angiotensin II induced contraction in five isolated smooth muscle assays

Eur J Pharmacol. 1993 Aug 24;240(2-3):147-54. doi: 10.1016/0014-2999(93)90892-l.

Abstract

Antagonist effect of losartan, a nonpeptide antagonist of angiotensin II, on angiotensin II induced contractile response was studied in five isolated smooth muscle assays. In the rabbit aorta and guinea-pig stomach assays, losartan competed with angiotensin II for the angiotensin receptors in an apparently simple manner, that is compliance with the basic criteria of Schild analysis for simple competition. Noncompliance, however, was observed in the guinea-pig ileum, rat ileum and guinea-pig trachea assays where losartan induced nonparallel rightward shifts of angiotensin II E/log[A] curves and the Schild plots were found to have slopes greater than unity. The observed deviations from simple competitive antagonism appeared to be different from those reported earlier, and a possible explanation involving tissue-dependent noncompetitive factor(s) is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / antagonists & inhibitors*
  • Angiotensin II / pharmacology
  • Animals
  • Aorta / drug effects
  • Biphenyl Compounds / pharmacology*
  • Guinea Pigs
  • Ileum / drug effects
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • Losartan
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / physiology
  • Rabbits
  • Stomach / drug effects
  • Tetrazoles / pharmacology*
  • Trachea / drug effects

Substances

  • Biphenyl Compounds
  • Imidazoles
  • Tetrazoles
  • Angiotensin II
  • Losartan