Orexinergic activation of medullary premotor neurons mediates the adrenal sympathoexcitation to hypothalamic glucoprivation

Glucoprivation activates neurons in the perifornical hypothalamus (PeH) and in the rostral ventrolateral medulla (RVLM), which results in release of adrenaline. The current study aimed to establish in vivo (i) whether neuroglucoprivation in the PeH or in the RVLM elicits adrenaline release; and (ii) whether direct activation of RVLM neurons by glucoprivation or the orexinergic drive to the RVLM mediates the release of adrenaline. Neuroglucoprivation in the PeH or RVLM was elicited by microinjections of 2-deoxy-D-glucose or 5-thio-D-glucose in anesthetized, euglycemic, rats. We found that 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 elicited an increase in 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 glucoprivation in the PeH elicits orexin release in the RVLM, capable of activating adrenal medullary presympathetic neurons in the RVLM.1 page(s