Cardiorespiratory anomalies in mice lacking CB1 cannabinoid receptors

PLoS One. 2014 Jun 20;9(6):e100536. doi: 10.1371/journal.pone.0100536. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Antagonists / pharmacology
  • Animals
  • Arterial Pressure / drug effects
  • Arterial Pressure / genetics
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Cardiovascular Physiological Phenomena* / drug effects
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology
  • Diet, High-Fat / adverse effects
  • Heart Rate / drug effects
  • Heart Rate / genetics
  • Male
  • Mice
  • Mice, Knockout*
  • Phenotype
  • Receptor, Cannabinoid, CB1 / deficiency*
  • Receptor, Cannabinoid, CB1 / genetics*
  • Respiration / drug effects
  • Respiration / genetics
  • Respiratory Physiological Phenomena* / drug effects
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Sleep / drug effects
  • Sleep / genetics
  • Sleep / physiology
  • Wakefulness / drug effects
  • Wakefulness / genetics
  • Wakefulness / physiology

Substances

  • Adrenergic Antagonists
  • Receptor, Cannabinoid, CB1

Grants and funding

This work was funded by Bologna University (RFO 2010 and 2011 http://www.unibo.it/Portale/Ricerca/Servizi+Docenti+Ricercatori/finanziamentinaz/RFO+-+Finanziamento+alla+ricerca+di+base.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.