title: Orexinergic activation of medullary premotor neurons modulates the adrenal sympathoexcitation to hypothalamic glucoprivation.
abstract: Glucoprivation activates neurons in the perifornical hypothalamus (PeH) and in the rostral ventrolateral medulla (RVLM), which results in the release of adrenaline. The current study aimed to establish 1) whether neuroglucoprivation in the PeH or in the RVLM elicits adrenaline release in vivo and 2) whether direct activation by glucoprivation or orexin release in the RVLM modulates the adrenaline release. Neuroglucoprivation in the PeH or RVLM was elicited by microinjections of 2-deoxy-D-glucose or 5-thio-D-glucose in anesthetized, euglycemic rats. Firstly, inhibition of neurons in the PeH abolished the increase in adrenal sympathetic nerve activity (ASNA) to systemic glucoprivation. Secondly, glucoprivation of neurons in the PeH increased ASNA. Thirdly, in vivo or in vitro glucoprivation did not affect the activity of RVLM adrenal premotor neurons. Finally, blockade of orexin receptors in the RVLM abolished the increase in ASNA to neuroglucoprivation in the PeH. The evoked changes in ASNA were directly correlated to levels of plasma metanephrine but not to normetanephrine. These findings suggest that orexin release modulates the activation of adrenal presympathetic neurons in the RVLM.
authors.affiliation: Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia willian.korim@unimelb.edu.au.
authors.forename: Willian S
authors.initials: WS
authors.lastname: Korim
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Lama
authors.initials: L
authors.lastname: Bou Farah
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: McMullan
authors.affiliation: Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Anthony J M
authors.initials: AJ
authors.lastname: Verberne
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism*; D005947:Glucose / Q000031:analogs & derivatives; D007031:Hypothalamus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000503:physiopathology*; D008676:Metanephrine / Q000097:blood; D008845:Microinjections; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; C003002:5-thio-D-glucose; D008676:Metanephrine; D005947:Glucose; D004837:Epinephrine