Cardiorespiratory anomalies in mice lacking CB1 cannabinoid receptors
PLoS ONE. 2014-06-20; 9(6): e100536
DOI: 10.1371/journal.pone.0100536
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Silvani A(1), Berteotti C(1), Bastianini S(1), Cohen G(2), Lo Martire V(1), Mazza
R(3), Pagotto U(3), Quarta C(3), Zoccoli G(1).
Author information:
(1)PRISM Lab, Department of Biomedical and Neuromotor Sciences, Alma Mater
Studiorum – University of Bologna, Bologna, Italy.
(2)Department of Women & Child Health, Karolinska Institutet, Stockholm, Sweden.
(3)Endocrinology Unit and Center for Applied Biomedical Research, Department of
Medical and Surgical Sciences, S. Orsola University Hospital, Alma Mater
Studiorum – University of Bologna, Bologna, Italy.
Cannabinoid type 1 (CB1) receptors are expressed in the nervous and
cardiovascular systems. In mice, CB1 receptor deficiency protects from metabolic
consequences of a high-fat diet (HFD), increases sympathetic activity to brown
fat, and entails sleep anomalies. We investigated whether sleep-wake and
diet-dependent cardiorespiratory control is altered in mice lacking CB1
receptors. CB1 receptor knock-out (KO) and intact wild-type (WT) mice were fed
standard diet or a HFD for 3 months, and implanted with a telemetric arterial
pressure transducer and electrodes for sleep scoring. Sleep state was assessed
together with arterial pressure and heart rate (home cage), or breathing
(whole-body plethysmograph). Increases in arterial pressure and heart rate on
passing from the light (rest) to the dark (activity) period in the KO were
significantly enhanced compared with the WT. These increases were unaffected by
cardiac (β1) or vascular (α1) adrenergic blockade. The breathing rhythm of the KO
during sleep was also more irregular than that of the WT. A HFD increased heart
rate, impaired cardiac vagal modulation, and blunted the central autonomic
cardiac control during sleep. A HFD also decreased cardiac baroreflex sensitivity
in the KO but not in the WT. In conclusion, we performed the first systematic
study of cardiovascular function in CB1 receptor deficient mice during
spontaneous wake-sleep behavior, and demonstrated that CB1 receptor KO alters
cardiorespiratory control particularly in the presence of a HFD. The CB1 receptor
signaling may thus play a role in physiological cardiorespiratory regulation and
protect from some adverse cardiovascular consequences of a HFD.