Effects of TCV-116 on endothelin-1 and PDGF A-chain expression in angiotensin II-induced hypertensive rats

Citation
K. Hara et al., Effects of TCV-116 on endothelin-1 and PDGF A-chain expression in angiotensin II-induced hypertensive rats, HYPERTENS R, 24(1), 2001, pp. 55-64
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
Hypertension research
ISSN journal
0916-9636 → ACNP
Volume
24
Issue
1
Year of publication
2001
Pages
55 - 64
Database
ISI
SICI code
Abstract
Angiotensin II(Ang II) has been shown to stimulate cardiac growth and colla gen synthesis in cultured vascular smooth muscle cells and to increase fibr oblast proliferation. Chronic infusion with Ang II increases blood pressure and activates growth mechanisms to produce hypertrophy of the heart. This study investigated the effects of an Ang II type 1 receptor antagonist, TCV -116, on preproendothelin-l (preproET-1), ETA receptor and platelet-derived growth factor(PDGF) A-chain expression in the left ventricle of Wistar-Kyo to rats treated for 2 weeks with Ang II (200 ng.kg(-1).min(-1)), and the re lation of these effects to myocardial remodeling. Rats given Ang II alone ( ANGII-V) were compared with rats also receiving TCV-116(ANGII-TCV), In both groups, blood pressure was similar and significantly higher than in contro l rats. The preproET-1, ETA receptor and PDGF A-chain expressions in the le ft ventricle were significantly increased in ANGII-V compared with control rats, and were significantly suppressed in ANGII-TCV compared with ANGII-V rats. ANGII-V rats showed a significant increase of the type I collagen exp ression, wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosi s, with all these parameters being significantly improved by TCV-116. Myoca rdial remodeling in Ang Ii-induced hypertensive rats was significantly amel iorated by a subdepressor dose of TCV-116, which may have been due to a dec rease in ET-1 and PDGF A-chain expression in the left ventricle.