Decompensated hemorrhage activates serotonergic neurons in the subependymal parapyramidal region of the rat medulla.
According to prior evidence opioid and serotonin release by lower brain stem neurons may contribute to hemorrhage-induced sympathoinhibition (HISI). Here we seek direct evidence for the activation of opioidergic, GABAergic, or serotonergic neurons by severe hemorrhage in the medulla oblongata. Blood was withdrawn from awake rats (40-50% total volume) causing hypotension and profound initial bradycardia. Other rats received the vasodilator hydralazine, causing tachycardia and hypotension. Neuronal activation was gauged by the presence of Fos-immunoreactive (ir) nuclei after 2 h. Serotonergic, enkephalinergic, and GABAergic neurons were identified by the presence of a diagnostic enzyme or mRNA. Hemorrhaged rats had 30% fewer non-GABAergic Fos-ir neurons in the rostral ventrolateral medulla (RVLM) than hydralazine-treated rats, but they had six times more Fos-ir neurons within the subependymal parapyramidal nucleus (SEPPN). Fos-labeled SEPPN neurons were serotonergic (40-60%), GABAergic (31%), enkephalinergic (15%), or had mixed phenotypes. The data suggest that a reduced sympathoexcitatory drive from RVLM may contribute to HISI. SEPPN neuronal activation may also contribute to HISI or could mediate defensive thermoregulatory mechanisms triggered by hemorrhage-induced hypothermia.
Department of Pharmacology, University of Virginia Health System, Charlottesville, Virginia 22908-0735, USA.
Nicole M
NM
Pelaez
Ann M
AM
Schreihofer
Patrice G
PG
Guyenet
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004745:Enkephalins / Q000235:genetics; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006830:Hydralazine / Q000494:pharmacology; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D011498:Protein Precursors / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D004745:Enkephalins; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014665:Vasodilator Agents; D006830:Hydralazine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; C033660:preproenkephalin