Orexins/hypocretins excite XXXX sympathetic preganglionic neurons in vivo and in vitro.

@entity1169 @entity22658 @entity3159 @entity4774 @entity4524 @entity35 @entity551
The two recently isolated hypothalamic peptides @entity22658 and orexin B, also known as hypocretin 1 and 2, are reported to be important signaling molecules in feeding and sleep/wakefulness. Orexin-containing neurons in the lateral hypothalamus project to numerous areas of the @entity35 brain and spinal cord including the intermediolateral cell column (IML) of the thoracolumbar spinal cord. An in vivo and in vitro study was undertaken to evaluate the hypothesis that orexins, acting on sympathetic preganglionic neurons (SPNs) in the @entity35 spinal cord, increase sympathetic outflow. First, @entity22658 (0.3, 1, and 10 nmol) by intrathecal injection increased mean arterial pressure (MAP) and heart rate (HR) by an average of 5, 18, and 30 mmHg and 10, 42, and 85 beats/min in @entity4774 -anesthetized @entity35 . Intrathecal injection of saline had no significant effects. Orexin B (3 nmol) by intrathecal administration increased MAP and HR by an average of 11 mmHg and 40 beats/min. The pressor effects of @entity22658 were attenuated by prior intrathecal injection of @entity22658 antibodies (1:500 dilution) but not by normal serum albumin. Intravenous administration of the alpha(1)-adrenergic receptor antagonist @entity3159 (0.5 mg/kg) or the beta-adrenergic receptor antagonist @entity1169 (0.5 mg/kg) markedly diminished, respectively, the @entity22658 -induced @entity551 . Second, whole cell patch recordings were made from antidromically identified SPNs of spinal cord slices from 12- to 16-day-old @entity35 . Superfusion of @entity22658 or orexin B (100 or 300 nM) excited 12 of 17 SPNs, as evidenced by a membrane depolarization and/or increase of neuronal discharges. @entity22658 - or B-induced depolarizations persisted in @entity4524 (0.5 microM)-containing Krebs solution, indicating that the peptide acted directly on SPNs. Results from our in vivo and in vitro studies together with the previous observation of the presence of @entity22658 -immunoreactive fibers in the IML suggest that orexins, when released within the IML, augment sympathetic outflow by acting directly on SPNs.
