title: Acute hypoxia activates neuroendocrine, but not presympathetic, neurons in the paraventricular nucleus of the hypothalamus: differential role of nitric oxide.
abstract: Hypoxia results in decreased arterial Po2, arterial chemoreflex activation, and compensatory increases in breathing, sympathetic outflow, and neuroendocrine secretions, including increased secretion of AVP, corticotropin-releasing hormone (CRH), adrenocorticotropin hormone (ACTH), and corticosterone. In addition to a brain stem pathway, including the nucleus tractus solitarius (nTS) and the rostral ventrolateral medulla (RVLM), medullary pathways to the paraventricular nucleus of the hypothalamus (PVN) contribute to chemoreflex responses. Experiments evaluated activation of specific cell phenotypes within the PVN following an acute hypoxic stimulus (AH; 2 h, 10% O2) in conscious rats. Retrograde tracers (from spinal cord and RVLM) labeled presympathetic (PreS) neurons, and immunohistochemistry identified AVP- and CRH-immunoreactive (IR) cells. c-Fos-IR was an index of neuronal activation. Hypoxia activated AVP-IR (~6%) and CRH-IR (~15%) cells, but not PreS cells in the PVN, suggesting that sympathoexcitation during moderate AH is mediated mainly by a pathway that does not include PreS neurons in the PVN. Approximately 14 to 17% of all PVN cell phenotypes examined expressed neuronal nitric oxide synthase (nNOS-IR). AH activated only nNOS-negative AVP-IR neurons. In contrast ~23% of activated CRH-IR neurons in the PVN contained nNOS. In the median eminence, CRH-IR terminals were closely opposed to tanycyte processes and end-feet (vimentin-IR) in the external zone, where vascular NO participates in tanycyte retraction to facilitate neuropeptide secretion into the pituitary portal circulation. Results are consistent with an inhibitory role of NO on AVP and PreS neurons in the PVN and an excitatory role of NO on CRH secretion in the PVN and median eminence.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri.
authors.forename: K Max
authors.initials: KM
authors.lastname: Coldren
authors.affiliation: Department of Critical Care, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Li
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri.|Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri.|Interdisciplinary Neuroscience Program, University of Missouri, Columbia, Missouri.
authors.forename: David D
authors.identifier: 0000-0003-3269-0184
authors.initials: DD
authors.lastname: Kline
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri.|Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri.|Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri; and.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Hasser
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri; HeeschC@missouri.edu.|Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri.|Interdisciplinary Neuroscience Program, University of Missouri, Columbia, Missouri.
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Heesch
mesh_terms: D000208:Acute Disease; D000320:Adrenergic Fibers / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004195:Disease Models, Animal; D063928:Ependymoglial Cells / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009433:Neural Inhibition; D055099:Neuroendocrine Cells / Q000378:metabolism*; D026602:Nitrergic Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism* / Q000503:physiopathology; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D014746:Vimentin / Q000378:metabolism
chemical_list: D014746:Vimentin; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D003346:Corticotropin-Releasing Hormone; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat
keywords: AVP; CRH; corticotropin-releasing hormone; median eminence; nitric oxide; vasopressin