Angiotensin II receptor antagonist, L-158,809, prevents intimal hyperplasia in dog grafted veins.
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.
Yuda
A
A
Departments of Pharmacology, Osaka Medical College, Takatsuki City, Japan.
Takai
S
S
Jin
D
D
Sawada
Y
Y
Nishimoto
M
M
Matsuyama
N
N
Asada
K
K
Kondo
K
K
Sasaki
S
S
Miyazaki
M
M
D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D004285:Dogs; D006965:Hyperplasia; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D010919:Placebos; D011945:Receptors, Angiotensin / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D014680:Veins / Q000187:drug effects* / Q000473:pathology
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D010919:Placebos; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C070967:L 158809