on October 21, 2002
Published online before print October 21, 2002, doi: 10.1161/01.HYP.0000039960.66987.89
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Submitted on April 30, 2002
From the Department of Internal Medicine,
Cardiovascular Division, Hyogo College of Medicine,
Nishinomiya, Japan. * To whom correspondence should be addressed. E-mail: ttsujino{at}hyo-med.ac.jp.
Abstract—There
are several controversies concerning the enhanced gene expression of
cardiac renin-angiotensin system components in
spontaneously hypertensive rats (SHR) compared with their normotensive
control Wistar-Kyoto (WKY) rats. We hypothesized that these
discrepancies arise from circadian fluctuations in gene expression. We
examined the circadian mRNA expression of renin,
angiotensinogen, ACE, and angiotensin type 1a
(AT1a) and type 2 (AT2) receptors in the hearts of SHR and WKY rats by
real-time quantitative reverse transcription-polymerase chain
reaction. The cardiac mRNA expression of the
renin-angiotensin system components showed circadian
oscillations in both SHR and WKY rats. The amplitudes of
these circadian fluctuations were greater in the SHR than in the WKY
rats. The mRNA levels of the renin-angiotensin system
components were also increased in the SHR compared with the WKY rats at
many time points (especially during the dark phase). However, the
levels of ACE, AT1a receptor, and AT2 receptor mRNA in the SHR and WKY
rats were almost the same during the late light phase. In contrast to
mRNA expression, ACE activity was similar both at the time of maximum
and minimum mRNA expression. The AT1 receptor antagonist
candesartan upregulated AT1a receptor mRNA and downregulated ACE mRNA
at specific time points only in the SHR group. Our findings of
differential diurnal expression of cardiac
renin-angiotensin system genes in SHR and WKY rats appear
to explain the discrepancies between prior studies. However, the
physiological relevance of the differential
circadian mRNA expression of the renin-angiotensin system
components remains to be elucidated.
Revised on May 21, 2002
Augmented Diurnal Variations of the Cardiac
Renin-Angiotensin System in Hypertensive
Rats
Yoshiro Naito;
Key words: circadian rhythm • renin-angiotensin system • renin • angiotensinogen • angiotensin-converting enzyme • receptors, angiotensin II • rats, spontaneously hypertensive
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