Reduced α‐adrenoceptor responsiveness and enhanced baroreflex sensitivity in Cry‐deficient mice lacking a biological clock

• Published in: The Journal of physiology Vol. 566; no. 1; pp. 213 - 224
• Main Authors: Masuki, Shizue, Todo, Takeshi, Nakano, Yasushi, Okamura, Hitoshi, Nose, Hiroshi
• Format: Journal Article
• Language: English
• Published: 9600 Garsington Road , Oxford , OX4 2DQ , UK Blackwell Science Ltd 01.07.2005; Blackwell Science Inc
• Subjects: Adrenergic alpha-Agonists - pharmacology; Animals; Baroreflex - drug effects; Baroreflex - physiology; Biological Clocks - drug effects; Biological Clocks - physiology; Blood Pressure - drug effects; Blood Pressure - physiology; Circadian Rhythm - drug effects; Circadian Rhythm - physiology; Cryptochromes; Flavoproteins - genetics; Flavoproteins - metabolism; Integrative Physiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Phenylephrine - pharmacology; Receptors, Adrenergic, alpha - metabolism
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2005.086728

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 α1‐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 α1‐adrenoceptor‐mediated vasoconstriction in peripheral vessels.