Intrathecal orexin A increases sympathetic outflow and respiratory drive, enhances baroreflex sensitivity and blocks the somato-sympathetic reflex

Br J Pharmacol. 2011 Feb;162(4):961-73. doi: 10.1111/j.1476-5381.2010.01102.x.


Background: Intrathecal (i.t.) injection of orexin A (OX-A) increases blood pressure and heart rate (HR), but the effects of OX-A on sympathetic and phrenic, nerve activity, and the baroreflex(es), somato-sympathetic and hypoxic chemoreflex(es) are unknown.

Experimental approach: Urethane-anaesthetized, vagotomized and artificially ventilated male Sprague-Dawley rats were examined in this study. The effects of i.t. OX-A (20 nmol 10 µL⁻¹) on cardiorespiratory parameters, and responses to stimulation of the sciatic nerve (electrical), arterial baroreceptors (phenylephrine hydrochloride, 0.01 mg kg⁻¹ i.v.) and peripheral (hypoxia) chemoreceptors were also investigated.

Key results: i.t. OX-A caused a prolonged dose-dependent sympathoexcitation, pressor response and tachycardia. The peak effect was observed at 20 nmol with increases in mean arterial pressure, HR and splanchnic sympathetic nerve activity (sSNA) of 32 mmHg, 52 beats per minute and 100% from baseline respectively. OX-A also dose-dependently increased respiratory drive, as indicated by a rise in phrenic nerve amplitude and a fall in phrenic nerve frequency, an increase in neural minute ventilation, a lengthening of the expiratory period, and a shortening of the inspiratory period. All effects of OX-A (20 nmol) were attenuated by the orexin receptor 1 antagonist SB 334867. OX-A significantly reduced both sympathoexcitatory peaks of somato-sympathetic reflex while increasing baroreflex sensitivity. OX-A increased the amplitude of the pressor response and markedly amplified the effect of hypoxia on sSNA.

Conclusions: Thus, activation of OX receptors in rat spinal cord alters cardiorespiratory function and differentially modulates sympathetic reflexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia, Spinal
  • Animals
  • Baroreflex / drug effects
  • Baroreflex / physiology*
  • Benzoxazoles / pharmacology
  • Evoked Potentials, Somatosensory / drug effects
  • Injections, Spinal
  • Intracellular Signaling Peptides and Proteins / administration & dosage
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Kinetics
  • Male
  • Naphthyridines
  • Neurons / drug effects
  • Neurons / physiology
  • Neuropeptides / administration & dosage
  • Neuropeptides / antagonists & inhibitors
  • Neuropeptides / physiology*
  • Orexin Receptors
  • Orexins
  • Peripheral Nervous System / drug effects
  • Peripheral Nervous System / physiology
  • Phrenic Nerve / drug effects
  • Phrenic Nerve / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Respiration* / drug effects
  • Splanchnic Nerves / drug effects
  • Splanchnic Nerves / physiology*
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology*
  • Tachycardia / chemically induced
  • Urea / analogs & derivatives
  • Urea / pharmacology
  • Vagotomy


  • 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
  • Benzoxazoles
  • Intracellular Signaling Peptides and Proteins
  • Naphthyridines
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Urea