3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors prevent the development of cardiac hypertrophy and heart failure in rats.
OBJECTIVE
The aim of the present study was to determine whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have preventive effects on the development of cardiac hypertrophy and heart failure.


BACKGROUND
Statins have been reported to have various pleiotropic effects, such as inhibition of inflammation and cell proliferation.


METHODS
Dahl rats were divided into three groups: LS, the rats fed the low-salt diet (0.3% NaCl); HS, the rats fed the high-salt diet (8% NaCl) from the age of 6 weeks; and CERI, the rats fed the high-salt diet with cerivastatin 1 mg/kg/d by gavage from the age of 6 weeks.


RESULTS
In HS rats, cardiac function was markedly impaired and all rats showed the signs of heart failure within 17 weeks of age. In CERI rats, cardiac function was better than that of HS and no rats were dead up to 17 weeks of age. The development of cardiac hypertrophy and fibrosis was attenuated, and the number of apoptotic cells and expression of proinflammatory cytokine interleukin (IL)-1beta gene were less as compared with HS rats. Pretreatment of cerivastatin suppressed the adriamycin-induced apoptosis of cultured cardiomyocytes of neonatal rats.


CONCLUSIONS
These results suggest that statins have a protective effect on cardiac myocytes and may be useful to prevent the development of hypertensive heart failure.
Hasegawa
Hiroshi
H
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine (M4), 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Yamamoto
Rie
R
Takano
Hiroyuki
H
Mizukami
Miho
M
Asakawa
Masayuki
M
Nagai
Toshio
T
Komuro
Issei
I
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D013997:Time Factors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007375:Interleukin-1; D011725:Pyridines; D017673:Sodium Chloride, Dietary; C086276:cerivastatin