Angiotensin II type I receptor antagonist inhibits the gene expression of transforming growth factor-beta1 and extracellular matrix in cardiac and vascular tissues of hypertensive rats

Item Type:	Article
Title:	Angiotensin II type I receptor antagonist inhibits the gene expression of transforming growth factor-beta1 and extracellular matrix in cardiac and vascular tissues of hypertensive rats
Creators Name:	Kim, S.K. and Ohta, K. and Hamaguchi, A. and Omura, T. and Yukimura, T. and Miura, K. and Inada, Y. and Ishimura, Y. and Chatani, F. and Iwao, H.
Abstract:	TCV-116 [(+/-)-(cyclohexyloxycarbony-loxy)ethyl2-ethoxy-1-[[2' -(1H- tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate ], a nonpeptide selective angiotensin II type I receptor (AT1 receptor) antagonist, at the dose of 0.1, 1 or 10 mg kg-1 day-1, was orally given to 22-week-old stroke-prone spontaneously hypertensive rats (SHRSP) for 10 weeks (from the age of 22-32 weeks) to examine the effects on gene expression of transforming growth factor-beta 1 (TGF-beta 1) and extracellular matrix proteins in the heart and blood vessels. Tissue messenger RNA (mRNA) was measured by northern blot analysis, with a specific complementary DNA probe. In the heart, left ventricular mRNA levels for fibronectin; types I, III and IV collagen; and laminin were significantly higher in SHRSP than control Wistar-Kyoto rats. In the mesenteric artery and aorta of SHRSP, TGF-beta 1 mRNA and the mentioned extracellular matrix protein mRNAs were increased compared with Wistar-Kyoto rats. Thus, the expression of various genes was up-regulated in cardiovascular tissues of SHRSP. Treatment of SHRSP with TCV-116 suppressed the gene expression of the mentioned extracellular matrix proteins and TGF-beta 1 in both heart and blood vessels in a dose-dependent fashion. Furthermore, TCV-116 regressed cardiac hypertrophy and lessened the medial hypertrophy of the aorta in SHRSP. These results show that angiotensin AT1 receptor antagonist in vivo can inhibit the gene expression of TGF-beta 1 and extracellular matrix proteins in hypertensive cardiovascular tissues. These effects may contribute to the beneficial effects of AT1 receptor antagonist on hypertensive cardiac hypertrophy and vascular thickening.
Keywords:	Angiotensin II, Aorta, Benzimidazoles, Biphenyl Compounds, Cardiomegaly, Enalapril, Extracellular Matrix Proteins, Gene Expression Regulation, Hypertension, Mesenteric Arteries, Myocardium, Messenger RNA, Inbred SHR Rats, Inbred WKY Rats, Angiotensin Receptors, Tetrazole, Transforming Growth Factor beta, Animals, Rats
Source:	Journal of Pharmacology and Experimental Therapeutics
ISSN:	0022-3565
Publisher:	American Society for Phamacology and Experimental Therapeutics
Volume:	273
Number:	1
Page Range:	509-515
Date:	April 1995
Official Publication:	http://jpet.aspetjournals.org/content/273/1/509.abstract
PubMed:	View item in PubMed

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