Hypothalamic Modulation of Adrenal Sympathetic Nerve Activity and the Glucose Counter‐Regulatory Response: Involvement of Medullary and Spinal Glutamate Receptors

Abstract

The rostral ventrolateral medulla (RVLM) and perifornical hypothalamus (PeF) control adrenaline release during the glucose counter-regulatory response (GCRR) but the circuitry is not well-defined. In anesthetised rats, we measured ASNA after RVLM or PeF electrical stimulation (0.5Hz, 50-400µA, 1ms). We gave intrathecal kynurenate (KYN; 5µmol/10μl) or vehicle before stimulation and 2-deoxyglucose (2-DG) iv or into PeF after KYN or vehicle into RVLM. Hexamethonium (hex; 20-40mg/kg iv) discriminated pre- and post-ganglionic ASNA responses. In other rats, we injected the tracer CTB into the adrenal medulla and immunoperoxidase stained cord sections for CTB+orexin. After RVLM stimulation, ASNA showed pre- or post-ganglionic early peaks (63±3 ms; 56±6 ms) and pre- or post-ganglionic late peaks (132±7 ms; 139±4 ms). Intrathecal KYN reduced all peaks (P<0.05). After PeF stimulation, ASNA consisted of pre- or post-ganglionic early peaks (84±1 ms; 91±1 ms) and pre- or post-ganglionic late peaks (133±2 ms; 143±2 ms). Hex reduced or abolished all RVLM-evoked peaks but only the PeF-evoked early peak (P<0.05). KYN in RVLM (5nmol/100nl) reduced (P<0.05) ASNA after iv and PeF 2-DG. Orexin terminals apposed sympathoadrenal neurons in the spinal cord. These data implicate a monosynaptic PeF-spinal pathway, long latency pre-ganglionic responses and orexin input in control of adrenaline release. Glutamatergic circuits including PeF, RVLM and spinal cord may underpin the GCRR.