Hemorrhagic hypotension-induced hypersensitivity of vagal pulmonary C-fibers to chemical stimulation and lung inflation in anesthetized rats

Am J Physiol Regul Integr Comp Physiol. 2015 Apr 1;308(7):R605-13. doi: 10.1152/ajpregu.00424.2014. Epub 2015 Jan 14.


This study was carried out to investigate whether hemorrhagic hypotension (HH) altered the sensitivity of vagal pulmonary C-fibers. The fiber activity (FA) of single vagal pulmonary C-fiber was continuously recorded in anesthetized rats before, during, and after HH was induced by bleeding from the femoral arterial catheter into a blood reservoir and lowering the mean systemic arterial pressure (MSAP) to ∼40 mmHg for 20 min. Our results showed the following. First, after MSAP reached a steady state of HH, the peak FA response to intravenous injection of capsaicin was elevated by approximately fivefold. The enhanced C-fiber sensitivity continued to increase during HH and sustained even after MSAP returned to baseline during the recovery, but slowly returned to control ∼20 min later. Second, responses of FA to intravenous injections of other chemical stimulants of pulmonary C-fibers (phenylbiguanide, lactic acid, and adenosine) and a constant-pressure lung hyperinflation were all significantly potentiated by HH. Third, infusion of sodium bicarbonate alleviated the systemic acidosis during HH, and it also attenuated, but did not completely prevent, the HH-induced C-fiber hypersensitivity. In conclusion, the pulmonary C-fiber sensitivity was elevated during HH, probably caused by the endogenous release of chemical substances (e.g., lactic acid) that were produced by tissue ischemia during HH. This enhanced C-fiber sensitivity may heighten the pulmonary protective reflexes mediated through these afferents (e.g., cough, J reflex) during hemorrhage when the body is more susceptible to other hazardous insults and pathophysiological stresses.

Keywords: C-fiber; hemorrhage; hypersensitivity; hypoxia; pulmonary.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials
  • Animals
  • Arterial Pressure
  • Chemoreceptor Cells / drug effects*
  • Chemoreceptor Cells / metabolism
  • Disease Models, Animal
  • Hemorrhage / complications*
  • Hemorrhage / physiopathology
  • Hydrogen-Ion Concentration
  • Hypotension / etiology*
  • Hypotension / metabolism
  • Hypotension / physiopathology
  • Lactic Acid / blood
  • Lung / innervation*
  • Male
  • Mechanoreceptors / drug effects*
  • Mechanoreceptors / metabolism
  • Mechanotransduction, Cellular
  • Nerve Fibers, Unmyelinated / drug effects*
  • Nerve Fibers, Unmyelinated / metabolism
  • Rats, Sprague-Dawley
  • Reflex
  • Sensory Thresholds / drug effects*
  • Stimulation, Chemical
  • Time Factors
  • Vagus Nerve / drug effects*
  • Vagus Nerve / metabolism
  • Vagus Nerve / physiopathology


  • Lactic Acid