Reduced alpha-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 microg kg(-1) of phenylephrine, an alpha1-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 alpha(1)-adrenoceptor-mediated vasoconstriction in peripheral vessels.
Masuki
Shizue
S
Department of Sports Medical Sciences, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan.
Todo
Takeshi
T
Nakano
Yasushi
Y
Okamura
Hitoshi
H
Nose
Hiroshi
H
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D056931:Cryptochromes; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D056931:Cryptochromes; D005420:Flavoproteins; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine