Role of angiotensin II in extracellular matrix and transforming growth factor-beta 1 expression in hypertensive rats.
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.
Ohta
K
K
Department of Pharmacology, Osaka City University Medical School, Japan.
Kim
S
S
Hamaguchi
A
A
Yukimura
T
T
Miura
K
K
Takaori
K
K
Iwao
H
H
D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; C084927:forasartan; D000804:Angiotensin II; D003094:Collagen; D002216:Captopril; C046835:alacepril