Blockade of orexin receptors with Almorexant reduces cardiorespiratory responses evoked from the hypothalamus but not baro- or chemoreceptor reflex responses

Kamon Iigaya, Jouji Horiuchi, Lachlan M. McDowall, Alex C B Lam, Yusuf Sediqi, Jaimie W. Polson, Pascal Carrive*, Roger A L Dampney

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Orexin neurons form a restricted group in the dorsal hypothalamus. The group is centered on the perifornical area within the classic hypothalamic defense area, an area which when activated produces marked cardiovascular and respiratory effects. Central administration of orexin can produce cardiorespiratory effects, but the extent to which orexin contributes to such responses evoked from the perifornical hypothalamus is not clear. To determine this, we used the dual orexin receptor antagonist Almorexant to challenge the cardiorespiratory effects evoked by disinhibition of the perifornical hypothalamus. Bicuculline (10 and 20 pmol) was microinjected in the perifornical area before and after administration of Almorexant (15 mg/kg iv) or vehicle in urethane-anesthetized rats. Almorexant significantly reduced the pressor, tachycardic, renal sympathoexcitatory, and tachypneic responses to bicuculline (10 pmol, by 55%, 53%, 28%, 77%; 20 pmol, by 54%, 27%, 51%, 72%, respectively). Reductions of similar magnitude were observed with bicuculline microinjections centered on more caudal sites just peripheral to the orexin neuron group, which would likely have activated fewer orexin neurons. In contrast, Almorexant had no effect on the cardiorespiratory response of the chemoreflex (sodium cyanide injection) or the sympathetic component of the baroreflex. Thus orexin makes a major contribution to the cardiorespiratory response evoked from the perifornical area even though orexin neurons represent only a fraction of the output of this area. Orexin neurons may also mediate cardiorespiratory responses from non-orexin neurons in the caudal hypothalamus. However, under resting conditions, blockade of orexin receptors does not affect the chemo- and baroreflexes.

Original languageEnglish
Pages (from-to)R1011-R1022
Number of pages12
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume303
Issue number10
DOIs
Publication statusPublished - 15 Nov 2012
Externally publishedYes

Keywords

  • Hypocretin
  • Perifornical area
  • Phrenic nerve activity
  • Sympathetic vasomotor activity

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