Abstract
The in vivo effects of alacepril (1-[(S)-3-acetylthio-2-methylpropanoyl]- L-prolyl-L-phenylalanine), an angiotensin converting enzyme inhibitor, and SC-52458 (5-[(3,5-dibutyl-1H-1,2,4-triazol-1- yl)methyl]-2-[2-(1H-tetrazol-5-ylphenyl)]pyridine), an angiotensin AT1 receptor antagonist, were examined on the cardiac and aortic gene expressions of extracellular matrices and TGF-beta 1 in young spontaneously hypertensive rats (SHR). In SHR, types I and III collagen mRNAs were increased in the left ventricle, and in contrast, fibronectin, collagen IV, and transforming growth factor-beta 1 (TGF-beta 1) mRNAs were increased in aorta, compared with those in Wistar-Kyoto rats. All the enhanced mRNAs in both organs in SHR were significantly inhibited by the short-term treatment with the above two drugs. Thus, angiotensin AT1 receptor may play an important role in the regulation of extracellular matrices and TGF-beta 1 expressions in SHR.
MeSH terms
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Angiotensin II / metabolism
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Angiotensin Receptor Antagonists*
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Angiotensin-Converting Enzyme Inhibitors / pharmacology*
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Animals
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Aorta / cytology
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Aorta / drug effects
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Blood Pressure / drug effects
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Blotting, Northern
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Captopril / analogs & derivatives*
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Captopril / pharmacology
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Collagen / genetics
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Collagen / metabolism
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Extracellular Matrix / drug effects
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Extracellular Matrix / genetics
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Extracellular Matrix / metabolism
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Gene Expression Regulation / drug effects*
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Gene Expression Regulation / genetics
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Heart Ventricles / cytology
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Heart Ventricles / drug effects
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Hypertension / metabolism
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Male
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Organ Size / drug effects
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Pyridines / pharmacology*
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RNA, Messenger / metabolism
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Rats
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Rats, Inbred SHR
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Rats, Inbred WKY
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Renin-Angiotensin System / drug effects
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Tetrazoles / pharmacology*
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Transforming Growth Factor beta / biosynthesis
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Transforming Growth Factor beta / genetics
Substances
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Angiotensin Receptor Antagonists
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Angiotensin-Converting Enzyme Inhibitors
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Pyridines
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RNA, Messenger
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Tetrazoles
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Transforming Growth Factor beta
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forasartan
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Angiotensin II
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Collagen
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Captopril
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alacepril