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Angiotensin II type I receptor antagonist inhibits the gene expression of transforming growth factor-beta 1 and extracellular matrix in cardiac and vascular tissues of hypertensive rats.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 1995 Apr; Vol. 273 (1), pp. 509-15. - Publication Year :
- 1995
-
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.
- Subjects :
- Animals
Aorta metabolism
Cardiomegaly drug therapy
Enalapril pharmacology
Male
Mesenteric Arteries metabolism
Myocardium metabolism
RNA, Messenger analysis
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Angiotensin II antagonists & inhibitors
Angiotensin Receptor Antagonists
Benzimidazoles pharmacology
Biphenyl Compounds pharmacology
Extracellular Matrix Proteins genetics
Gene Expression Regulation drug effects
Hypertension metabolism
Tetrazoles
Transforming Growth Factor beta genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 273
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 7714806