Acute intermittent hypoxia in rat in vivo elicits a robust increase in tonic sympathetic nerve activity that is independent of respiratory drive

J Physiol. 2010 Aug 15;588(Pt 16):3075-88. doi: 10.1113/jphysiol.2010.190454. Epub 2010 Jun 21.


Acute intermittent hypoxia (AIH) elicits long-term increases in respiratory and sympathetic outflow (long-term facilitation, LTF). It is still unclear whether sympathetic LTF is totally dependent on changes in respiration, even though respiratory drive modulates sympathetic nerve activity (SNA). In urethane-anaesthetized, vagotomized mechanically ventilated Sprague-Dawley rats, we investigated the effect of ten 45 s episodes of 10% O2-90% N(2) on splanchnic sympathetic nerve activity (sSNA) and phrenic nerve activity (PNA). We then tested whether or not hypoxic sympathetic chemoreceptor and baroreceptor reflexes were changed 60 min after AIH. We found that 17 animals manifested a sustained increase of sSNA (+51.2+/-4.7%) 60 min after AIH, but only 10 of these rats also expressed phrenic LTF compared with the time controls (rats not exposed to hypoxia, n=5). Inspiratory triggered averages of integrated sSNA showed respiratory modulation of SNA regardless of whether or not phrenic LTF had developed. The hypoxic chemoreceptor reflex was enhanced by 60 min after the development of AIH (peak change from 76.9+/-13.9 to 159.5+/-24.9%). Finally, sympathetic baroreceptor reflex sensitivity increased after sympathetic LTF was established (Gainmax from 1.79+/-0.18 to 2.60+/-0.28% mmHg1). Our findings indicate that respiratory-sympathetic coupling does contribute to sympathetic LTF, but that an additional tonic increase of sympathetic tone is also present that is independent of the level of PNA. Sympathetic LTF is not linked to the change in baroreflex function, since the baroreflex appears to be enhanced rather than impaired, but does play an important role in the enhancement of the hypoxic chemoreflex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Acute Disease
  • Animals
  • Baroreflex
  • Bicarbonates / blood
  • Blood Pressure
  • Carbon Dioxide / blood
  • Chemoreceptor Cells / metabolism
  • Disease Models, Animal
  • Heart Rate
  • Hydrogen-Ion Concentration
  • Hypoxia / metabolism
  • Hypoxia / physiopathology*
  • Long-Term Potentiation*
  • Male
  • Phrenic Nerve / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Respiration, Artificial
  • Respiratory Mechanics
  • Respiratory Muscles / innervation*
  • Splanchnic Nerves / physiopathology*
  • Sympathetic Nervous System / physiopathology*
  • Time Factors
  • Vagotomy


  • Bicarbonates
  • Carbon Dioxide