Blockade of orexin receptors reduces glutamatergic excitation of adrenal premotor neurons in the rostral ventrolateral medulla

Abstract

Excitation of adrenal sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) elicits epinephrine release as part of the glucose counter‐regulatory response to hypoglycemia. It is known that this response is partly mediated by excitatory inputs from hypothalamic orexin neurons. Although some orexin neurons co‐express glutamate, whether orexin and glutamate interact in order to facilitate adrenal sympathetic premotor neurons is unknown. In pentobarbitone‐anesthetized male Sprague‐Dawley rats, we show tested whether glutamatergic activation of adrenal premotor neurons depends on activation of orexin receptors (Ox‐R). Microinjection of glutamate (50 mM/50 nl) into the RVLM, where adrenal premotor neurons are found, increased adrenal sympathetic nerve activity (ASNA). The increase in ASNA was reduced following non‐selective blockade of orexin receptors. RVLM orexin receptors were blocked by microinjecting a combination of SB334867 (Ox1‐R antagonist) and TCS OX2 29 (Ox2‐R antagonist) into the RVLM. The reduction in ASNA in response to glutamate microinjection into the RVLM was dose dependent (0.1–10 mM/50 nl), and the response was abolished with 1 mM of the combined antagonists (P<0.05). The results suggest that the counter‐regulatory release of epinephrine during hypoglycemia depends on the interaction between glutamate and orexin receptors located on the adrenal sympathetic premotor neurons.Support or Funding InformationNHMRC AustraliaAustin Medical Research Foundation