Orexinergic Activation of Medullary Premotor Neurons Modulates the Adrenal Sympathoexcitation to Hypothalamic Glucoprivation
- 1Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
- 2Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia
- Corresponding author: Willian S. Korim, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1073/-/DC1.
- Received July 15, 2013.
- Accepted February 10, 2014.
- © 2014 by the American Diabetes Association.
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