Orexin A in rat rostral ventrolateral medulla is pressor, sympatho-excitatory, increases barosensitivity and attenuates the somato-sympathetic reflex

Br J Pharmacol. 2012 Apr;165(7):2292-303. doi: 10.1111/j.1476-5381.2011.01694.x.


Background and purpose: The rostral ventrolateral medulla (RVLM) maintains sympathetic nerve activity (SNA), and integrates adaptive reflexes. Orexin A-immunoreactive neurones in the lateral hypothalamus project to the RVLM. Microinjection of orexin A into RVLM increases blood pressure and heart rate. However, the expression of orexin receptors, and effects of orexin A in the RVLM on splanchnic SNA (sSNA), respiration and adaptive reflexes are unknown.

Experimental approach: The effect of orexin A on baseline cardio-respiratory variables as well as the somato-sympathetic, baroreceptor and chemoreceptor reflexes in RVLM were investigated in urethane-anaesthetized, vagotomized and artificially ventilated male Sprague-Dawley rats (n= 50). orexin A and its receptors were detected with fluorescence immunohistochemistry.

Key results: Tyrosine hydroxylase-immunoreactive neurones in the RVLM were frequently co-localized with orexin 1 (OX(1) ) and orexin 2 (OX(2) ) receptors and closely apposed to orexin A-immunoreactive terminals. Orexin A injected into the RVLM was pressor and sympatho-excitatory. Peak effects were observed at 50 pmol with increased mean arterial pressure (42 mmHg) and SNA (45%). Responses to orexin A (50 pmol) were attenuated by the OX(1) receptor antagonist, SB334867, and reproduced by the OX(2) receptor agonist, [Ala(11) , D-Leu(15) ]orexin B. Orexin A attenuated the somato-sympathetic reflex but increased baroreflex sensitivity. Orexin A increased or reduced sympatho-excitation following hypoxia or hypercapnia respectively.

Conclusions and implications: Although central cardio-respiratory control mechanisms at rest do not rely on orexin, responses to adaptive stimuli are dramatically affected by the functional state of orexin receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baroreflex / drug effects
  • Baroreflex / physiology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Chemoreceptor Cells / drug effects
  • Chemoreceptor Cells / physiology
  • Intracellular Signaling Peptides and Proteins / administration & dosage
  • Intracellular Signaling Peptides and Proteins / pharmacology*
  • Intracellular Signaling Peptides and Proteins / physiology
  • Male
  • Medulla Oblongata / drug effects*
  • Medulla Oblongata / physiology*
  • Neuropeptides / administration & dosage
  • Neuropeptides / pharmacology*
  • Neuropeptides / physiology
  • Orexin Receptors
  • Orexins
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / physiology
  • Receptors, Neuropeptide / agonists
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Receptors, Neuropeptide / physiology
  • Reflex / drug effects
  • Reflex / physiology
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology


  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide