Artikel
Inversion of circadian blood pressure rhythm by angiotensin II is accompanied by altered clock gene expression
Die Inversion des zirkadianen Blutdruckrhythmusses durch Angiotensin II korreliert mit veränderter kardiovaskulärer clock gene Expression
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Veröffentlicht: | 11. November 2004 |
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Gliederung
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Cardiovascular parameters underlie circadian rhythms and a disturbance of these rhythms in disease states is often accompanied by a poor prognosis. Circulating as well as central angiotensin II (Ang II) has been shown to significantly influence the circadian rhythm of blood pressure. Circadian rhythms in mammals are controlled by a group of specialized genes which are active in the suprachiasmatic nucleus of the hypothalamus and in peripheral tissues. We wondered whether these genes are also active and whether the renin angiotensin system (RAS) underlies a circadian control in tissues involved in cardiovascular regulation. Therefore, the gene expression of the clock genes, period (per1 and per 2), bmal1, clock, and D-binding protein (dbp), as well as of RAS components was quantified by real-time RT-PCR in the heart, aorta, kidney, lung, adrenal gland and liver at 4 time points around the clock (10:00 pm, 4:00 am, 10:00 am and 4:00 pm). Also, the effects of a low-dose Ang II infusion (subcutaneous for 7 days) were studied. In the investigated organs, clock and RAS genes showed a clear circadian alteration in mRNA levels. Ang II infusion inverted the circadian rhythm of blood pressure, as previously described. In parallel, Ang II inverted the circadian rhythm of kidney angiotensinogen (AOGEN) (57.9% increase vs. 59.0% decrease in control, from night to day period). Also, it altered the circadian rhythm of per1 and bmal1 in the kidney, of per1 and clock in aorta, and of AOGEN, per2 and clock in liver.
These results support the existence of independent circadian clocks in cardiovascular organs. Ang II inverts the circadian rhythm of blood pressure possibly by its influence on the expression of clock genes and AOGEN in these tissues.