Propofol-induced Inhibition of Catecholamine Release Is Reversed by Maintaining Calcium Influx

Anesthesiology. 2016 Apr;124(4):878-84. doi: 10.1097/ALN.0000000000001015.


Background: Propofol (2,6-diisopropylphenol) is one of the most frequently used anesthetic agents. One of the main side effects of propofol is to reduce blood pressure, which is thought to occur by inhibiting the release of catecholamines from sympathetic neurons. Here, the authors hypothesized that propofol-induced hypotension is not simply the result of suppression of the release mechanisms for catecholamines.

Methods: The authors simultaneously compared the effects of propofol on the release of norepinephrine triggered by high K-induced depolarization, as well as ionomycin, by using neuroendocrine PC12 cells and synaptosomes. Ionomycin, a Ca ionophore, directly induces Ca influx, thus bypassing the effect of ion channel modulation by propofol.

Results: Propofol decreased depolarization (high K)-triggered norepinephrine release, whereas it increased ionomycin-triggered release from both PC12 cells and synaptosomes. The propofol (30 μM)-induced increase in norepinephrine release triggered by ionomycin was dependent on both the presence and the concentration of extracellular Ca (0.3 to 10 mM; n = 6). The enhancement of norepinephrine release by propofol was observed in all tested concentrations of ionomycin (0.1 to 5 μM; n = 6).

Conclusions: Propofol at clinically relevant concentrations promotes the catecholamine release as long as Ca influx is supported. This unexpected finding will allow for a better understanding in preventing propofol-induced hypotension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Catecholamines / metabolism*
  • Cells, Cultured
  • Humans
  • Hypnotics and Sedatives / pharmacology*
  • Ionomycin / metabolism
  • Norepinephrine / metabolism
  • PC12 Cells / metabolism
  • Propofol / pharmacology*
  • Rats
  • Synaptosomes / metabolism


  • Catecholamines
  • Hypnotics and Sedatives
  • Ionomycin
  • Calcium
  • Norepinephrine
  • Propofol