title: Serotonin nerve terminals in the dorsomedial medulla facilitate sympathetic and ventilatory responses to hemorrhage and peripheral chemoreflex activation.
abstract: Serotonin neurons of the caudal raphe facilitate ventilatory and sympathetic responses that develop following blood loss in conscious rats. Here, we tested whether serotonin projections to the caudal portion of the dorsomedial brain stem (including regions of the nucleus tractus solitarius that receive cardiovascular and chemosensory afferents) contribute to cardiorespiratory compensation following hemorrhage. Injections of the serotonin neurotoxin 5,7-dihydroxytryptamine produced >90% depletion of serotonin nerve terminals in the region of injection. Withdrawal of ∼21% of blood volume over 10 min produced a characteristic three-phase response that included 1) a normotensive compensatory phase, 2) rapid sympathetic withdrawal and hypotension, and 3) rapid blood pressure recovery accompanied by slower recovery of heart rate and sympathetic activity. A gradual tachypnea developed throughout hemorrhage, which quickly reversed with the advent of sympathetic withdrawal. Subsequently, breathing frequency and neural minute volume (determined by diaphragmatic electromyography) declined below baseline following termination of hemorrhage but gradually recovered over time. Lesioned rats showed attenuated sympathetic and ventilatory responses during early compensation and later recovery from hemorrhage. Both ventilatory and sympathetic responses to chemoreceptor activation with potassium cyanide injection were attenuated by the lesion. In contrast, the gain of sympathetic and heart rate baroreflex responses was greater, and low-frequency oscillations in blood pressure were reduced after lesion. Together, the data are consistent with the view that serotonin innervation of the caudal dorsomedial brain stem contributes to sympathetic compensation during hypovolemia, possibly through facilitation of peripheral chemoreflex responses.
authors.affiliation: Neuroscience Institute and Department of Molecular Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA.
authors.forename: Ling-Hsuan
authors.initials: LH
authors.lastname: Kung
authors.forename: Karie E
authors.initials: KE
authors.lastname: Scrogin
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage; D000222:Adaptation, Physiological; D000818:Animals; D017704:Baroreflex; D001794:Blood Pressure; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D006339:Heart Rate; D006470:Hemorrhage / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007022:Hypotension / Q000378:metabolism / Q000503:physiopathology; D020896:Hypovolemia / Q000378:metabolism / Q000503:physiopathology; D007267:Injections; D007668:Kidney / Q000294:innervation; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D011190:Potassium Cyanide / Q000008:administration & dosage; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012123:Pulmonary Ventilation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018490:Serotonin Agents / Q000008:administration & dosage; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D011190:Potassium Cyanide