title: Orexin A in rat rostral ventrolateral medulla is pressor, sympatho-excitatory, increases barosensitivity and attenuates the somato-sympathetic reflex.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
authors.forename: Israt Z
authors.initials: IZ
authors.lastname: Shahid
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Rahman
authors.forename: Paul M
authors.initials: PM
authors.lastname: Pilowsky
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology*; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide