Cardiovascular effects of L-158,809, a new angiotensin type 1 receptor antagonist, assessed using the halothane-anesthetized in vivo canine model

Jpn J Pharmacol. 2002 Jun;89(2):192-6. doi: 10.1254/jjp.89.192.

Abstract

L-158,809 is a new angiotensin II type 1 receptor antagonist. We simultaneously assessed its antagonistic potency and cardiovascular effects with the halothane-anesthetized in vivo canine model (n = 5). L-158,809 was intravenously infused over 10 min at escalating doses of 0.03, 0.3 and 3 mg/kg. Angiotensin II (0.1 microg/kg, i.v.)-induced vasopressor and negative inotropic responses were significantly suppressed from the low dose L-158,809. Meanwhile, L-158,809 did not affect any of the cardiovascular parameters except that QTc was slightly shortened after the high dose administration. These results support the previous in vitro knowledge that L-158,809 is a highly selective angiotensin II receptor antagonist.

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin Receptor Antagonists*
  • Animals
  • Blood Pressure / drug effects
  • Cardiovascular System / drug effects*
  • Dogs
  • Dose-Response Relationship, Drug
  • Halothane / administration & dosage*
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology*
  • Models, Animal*
  • Receptors, Angiotensin / metabolism
  • Tetrazoles / administration & dosage
  • Tetrazoles / pharmacology*

Substances

  • Angiotensin Receptor Antagonists
  • Imidazoles
  • Receptors, Angiotensin
  • Tetrazoles
  • Angiotensin II
  • L 158809
  • Halothane