title: Cardiorespiratory anomalies in mice lacking CB1 cannabinoid receptors.
abstract: 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.
authors.affiliation: PRISM Lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Silvani
authors.affiliation: PRISM Lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Berteotti
authors.affiliation: PRISM Lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bastianini
authors.affiliation: Department of Women & Child Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gary
authors.initials: G
authors.lastname: Cohen
authors.affiliation: PRISM Lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Lo Martire
authors.affiliation: 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.
authors.forename: Roberta
authors.initials: R
authors.lastname: Mazza
authors.affiliation: 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.
authors.forename: Uberto
authors.initials: U
authors.lastname: Pagotto
authors.affiliation: 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.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Quarta
authors.affiliation: PRISM Lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zoccoli
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects / Q000235:genetics; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency* / Q000235:genetics*; D012119:Respiration / Q000187:drug effects / Q000235:genetics; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012890:Sleep / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D018674:Adrenergic Antagonists; D043884:Receptor, Cannabinoid, CB1