Ceramide mediates acute oxygen sensing in vascular tissues

Antioxid Redox Signal. 2014 Jan 1;20(1):1-14. doi: 10.1089/ars.2012.4752. Epub 2013 Aug 21.


Aims: A variety of vessels, such as resistance pulmonary arteries (PA) and fetoplacental arteries and the ductus arteriosus (DA) are specialized in sensing and responding to changes in oxygen tension. Despite opposite stimuli, normoxic DA contraction and hypoxic fetoplacental and PA vasoconstriction share some mechanistic features. Activation of neutral sphingomyelinase (nSMase) and subsequent ceramide production has been involved in hypoxic pulmonary vasoconstriction (HPV). Herein we aimed to study the possible role of nSMase-derived ceramide as a common factor in the acute oxygen-sensing function of specialized vascular tissues.

Results: The nSMase inhibitor GW4869 and an anticeramide antibody reduced the hypoxic vasoconstriction in chicken PA and chorioallantoic arteries (CA) and the normoxic contraction of chicken DA. Incubation with interference RNA targeted to SMPD3 also inhibited HPV. Moreover, ceramide and reactive oxygen species production were increased by hypoxia in PA and by normoxia in DA. Either bacterial sphingomyelinase or ceramide mimicked the contractile responses of hypoxia in PA and CA and those of normoxia in the DA. Furthermore, ceramide inhibited voltage-gated potassium currents present in smooth muscle cells from PA and DA. Finally, the role of nSMase in acute oxygen sensing was also observed in human PA and DA.

Innovation: These data provide evidence for the proposal that nSMase-derived ceramide is a critical player in acute oxygen-sensing in specialized vascular tissues.

Conclusion: Our results indicate that an increase in ceramide generation is involved in the vasoconstrictor responses induced by two opposite stimuli, such as hypoxia (in PA and CA) and normoxia (in DA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / pharmacology
  • Animals
  • Benzylidene Compounds / pharmacology
  • Blood Vessels / drug effects
  • Blood Vessels / metabolism*
  • Ceramides / metabolism*
  • Ceramides / pharmacology
  • Chick Embryo
  • Ductus Arteriosus / metabolism
  • Gene Expression
  • Humans
  • Hypoxia / metabolism
  • Oxygen / metabolism*
  • Pulmonary Artery / metabolism
  • Reactive Oxygen Species / metabolism
  • Shaw Potassium Channels / metabolism
  • Sphingomyelin Phosphodiesterase / antagonists & inhibitors
  • Sphingomyelin Phosphodiesterase / genetics
  • Sphingomyelin Phosphodiesterase / metabolism
  • Vasoconstriction / physiology


  • Aniline Compounds
  • Benzylidene Compounds
  • Ceramides
  • GW 4869
  • Reactive Oxygen Species
  • Shaw Potassium Channels
  • Sphingomyelin Phosphodiesterase
  • Oxygen