Angiotensin II receptor antagonist, L-158,809, prevents intimal hyperplasia in dog grafted veins

Life Sci. 2000 Nov 24;68(1):41-8. doi: 10.1016/s0024-3205(00)00910-3.

Abstract

We investigated the levels of the angiotensin II-forming enzymes, chymase and angiotensin converting enzyme (ACE), in dog grafted veins, and studied the effect of an angiotensin II type 1 receptor antagonist, L-158,809, on vascular proliferation in the grafted veins. The right external jugular vein was grafted to the ipsilaterial carotid artery. In the group treated with L-158,809, the drug (10 mg/kg per day, p.o.) were administered orally from 7 days before the operation to 28 days after it, while the others were administrated placebo. In the placebo-treated group, the chymase activity in the grafted veins was increased about 10-fold and the ACE activity was doubled. The areas of intima and media were significantly increased in the grafted veins in the placebo-treated group. L-158,809 significantly reduced the intimal area of the grafted veins. An angiotensin II receptor antagonist, L-158,809, prevented the vascular proliferation in the grafted veins, and the development of the proliferation may depend on activation of local angiotensin II formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin Receptor Antagonists*
  • Animals
  • Dogs
  • Hyperplasia
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • Placebos
  • Receptors, Angiotensin / metabolism
  • Tetrazoles / pharmacology*
  • Tunica Intima / drug effects*
  • Tunica Intima / pathology
  • Veins / drug effects*
  • Veins / pathology

Substances

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