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

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.