Angiotensin II receptor antagonist, L-158,809, prevents intimal hyperplasia in dog grafted veins.
Yuda A, Takai S, Jin D, Sawada Y, Nishimoto M, Matsuyama N, Asada K, Kondo K, Sasaki S, Miyazaki M.
Departments of Pharmacology, Osaka Medical College, Takatsuki City, Japan.
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.
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PMID: 11132244 [PubMed - indexed for MEDLINE]