Published Online
on June 30, 2003

A more recent version of this article appeared on August 1, 2003

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Submitted on February 21, 2003
Revised on March 18, 2003

Alterations of Circadian Expressions of Clock Genes in Dahl Salt-Sensitive Rats Fed a High-Salt Diet

Takao Mohri; Noriaki Emoto^*; Hidemi Nonaka; Hiroyuki Fukuya; Kazuhiro Yagita; Hitoshi Okamura; and Mitsuhiro Yokoyama

From the Division of Cardiovascular and Respiratory Medicine (T.M., N.E., H.N., H.F., M.Y.), Department of Internal Medicine, and the Division of Molecular Brain Science (K.Y., H.O.), Department of Brain Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.

^* To whom correspondence should be addressed. E-mail: emoto{at}med.kobe-u.ac.jp.

Abstract--In mammals, behavioral and physiologic processes display 24-hour rhythms that are regulated by a circadian system consisting of central and peripheral oscillators. Because various cardiovascular functions show diurnal variations and abnormal patterns of circadian blood pressure variation carry a high risk of cardiovascular complications, we investigated whether the expression of clock genes is altered in an animal model of hypertension. In Dahl salt-sensitive rats fed a high-salt (4% NaCl) diet for 6 weeks (DS-H), radiotelemetry monitoring showed increased amplitude of circadian variations in blood pressure. The ratio of heart weight to body weight and the ratio of kidney weight to body weight were higher in DS-H. Echocardiographic data showed that the wall thickness of the left ventricle was greater in DS-H. Northern blot analysis and single cosinor analysis revealed that the amplitudes of circadian expression changes of the clock genes (mPer2, Bmal1, and dbp) in the heart, liver, and kidney were significantly decreased in DS-H rats compared with a normal-salt-diet group, except for Bmal1 in the liver. The circadian expression changes of plasminogen activator inhibitor-1, a clock-regulated gene, were attenuated in the hearts of DS-H. The present results demonstrate that DS-H show altered circadian expression of peripheral clock genes. Detailed analyses of the relation between circadian expression of clock genes and blood pressure regulation might reveal a role for chronologic therapy of cardiovascular disease.

Key words: circadian rhythm • hypertension, experimental • hypertrophy • molecular biology • rats, Dahl

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