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-adrenoceptor responsiveness and enhanced baroreflex sensitivity in Cry-deficient mice lacking a biological clock
1 Department of Sports Medical Sciences, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan
2 Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan
3 Kissei Comtec Co., Matsumoto 390-1293, Japan
4 Department of Brain Science, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
To reveal the role of clock genes in generating the circadian rhythm of baroreflexes, we continuously measured mean arterial pressure and baroreflex sensitivity in free-moving normal wild-type mice, and in Cry-deficient mice which lack a circadian rhythm, in constant darkness for 24 h. In wild-type mice the mean arterial pressure was higher at night than during the day, and was accompanied by a significantly enhanced baroreflex sensitivity of –13.6 ± 0.8 at night compared with –9.7 ± 0.7 beats min–1 mmHg–1 during the day (P < 0.001). On the other hand, diurnal changes in arterial pressure disappeared in Cry-deficient mice with remarkably enhanced baroreflex sensitivity compared with wild-type mice (P < 0.001): –21.9 ± 1.6 at night and –23.1 ± 2.1 beats min–1 mmHg–1 during the day. Moreover, the mean arterial pressure response to 10 µg kg–1 of phenylephrine, an 
1-adrenoceptor agonist, was severely suppressed in Cry-deficient mice regardless of time, while that for the wild-type mice was 10.1 ± 1.9 mmHg in the night, significantly lower than 22.0 ± 3.5 mmHg in the day (P < 0.01). These results suggest that CRY genes are involved in generating the circadian rhythm of baroreflex sensitivity, partially by regulating 1-adrenoceptor-mediated vasoconstriction in peripheral vessels.
(Received 15 March 2005;
accepted after revision 21 April 2005;
first published online 28 April 2005)
Corresponding author H. Nose: Department of Sports Medical Sciences, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan. Email: nosehir{at}sch.md.shinshu-u.ac.jp
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