REM sleep deprivation induces endothelial dysfunction and hypertension in middle-aged rats: Roles of the eNOS/NO/cGMP pathway and supplementation with L-arginine

PLoS One. 2017 Aug 15;12(8):e0182746. doi: 10.1371/journal.pone.0182746. eCollection 2017.


Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes. The results showed that REM sleep deprivation decreased body weight, increased blood pressure, and impaired endothelial function of the aortas in middle-aged rats but not young rats. Moreover, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) concentrations as well as endothelial NO synthase (eNOS) phosphorylation in the aorta were decreased by REM sleep deprivation. Supplementation with L-arginine could protect against REM sleep deprivation-induced hypertension, endothelial dysfunction, and damage to the eNOS/NO/cGMP signaling pathway. The results of the present study suggested that REM sleep deprivation caused endothelial dysfunction and hypertension in middle-aged rats via the eNOS/NO/cGMP pathway and that these pathological changes could be inhibited via L-arginine supplementation. The present study provides a new strategy to inhibit the signaling pathways involved in insomnia-induced or insomnia-enhanced cardiovascular diseases.

MeSH terms

  • Animals
  • Arginine / pharmacology*
  • Blood Pressure / drug effects
  • Cyclic GMP / metabolism*
  • Hypertension / etiology*
  • Hypertension / metabolism
  • Male
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type III / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Sleep Deprivation / complications*
  • Sleep Deprivation / metabolism
  • Sleep Deprivation / physiopathology*


  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase Type III
  • Cyclic GMP

Grant support

The present study was supported by the Young Research Foundation of Shanghai Health Bureau (20144Y0152), the Shanghai Education Budget Foundation (2015YSN25), and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, China State Education Ministry (N138590). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.