Cardiac hypertrophy-related gene expression in spontaneously hypertensive rats: crucial role of angiotensin AT1 receptor.
Angiotensin converting-enzyme inhibitors (alacepril and imidapril) or an AT1-receptor antagonist (SC-52458) was administered to 10-week-old spontaneously hypertensive rats (SHR) for 7 days, and cardiac mRNA levels for contractile proteins and atrial natriuretic polypeptide (ANP) were comprehensively measured. The expression of skeletal alpha-actin and ANP was selectively enhanced in the heart of vehicle-treated SHR compared with Wistar-Kyoto rats (WKY), thereby suggesting that the phenotypic modulation of myocytes occurred at the early stage of hypertension. The above-mentioned three drugs similarly suppressed these enhanced gene expressions, nearly to the control levels. In contrast, although the treatment with hydralazine lowered the blood pressure of SHR similarly, hydralazine did not suppress ANP expression at all and only partially suppressed skeletal alpha-actin. Moreover, alacepril did not affect these gene expressions in WKY. Thus, AT1 receptor may be crucial for phenotypic modulation in the heart of SHR.
Ohta
K
K
Department of Pharmacology, Osaka City University Medical School, Japan.
Kim
S
S
Hamaguchi
A
A
Miura
K
K
Yukimura
T
T
Iwao
H
H
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D009320:Atrial Natriuretic Factor; D001345:Autoradiography; D015152:Blotting, Northern; D002216:Captopril / Q000031:analogs & derivatives / Q000494:pharmacology; D015870:Gene Expression; D006973:Hypertension; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000235:genetics*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D011725:Pyridines; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C084927:forasartan; D009320:Atrial Natriuretic Factor; D002216:Captopril; C046835:alacepril