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

Israt Z. Shahid, Ahmed A. Rahman, Paul M. Pilowsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2292-2303
Number of pages12
JournalBritish Journal of Pharmacology
Volume165
Issue number7
DOIs
Publication statusPublished - Apr 2012

Keywords

  • baroreflex
  • chemoreflex
  • orexin A
  • somato-sympathetic reflex
  • sympathetic vasomotor tone

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