title: Oxytocin neuron activation prevents hypertension that occurs with chronic intermittent hypoxia/hypercapnia in rats.
abstract: Hypertension is a common outcome associated with obstructive sleep apnea (OSA), a prevalent yet poorly treated cardiovascular disease. Recent studies showed oxytocin (OXT), released from hypothalamic paraventricular nucleus (PVN) neurons, activates cardiac vagal neurons in the dorsal motor nucleus of the vagus (DMNX) and may blunt cardiovascular responses to stress. This study tests whether the release of OXT from PVN fibers in the DMNX is diminished with chronic intermittent hypoxia-hypercapnia (CIH/H) exposure, an animal model of OSA, and whether activation of PVN OXT neurons restores OXT release in the DMNX and prevents the hypertension resulting from CIH/H. To assess OXT release from PVN fibers, Chinese hamster ovarian (CHO) cells were engineered to be highly sensitive to OXT by stable expression of the human recombinant OXT receptor and the calcium indicator R-GECO1. PVN fibers in the DMNX were selectively photoactivated in vitro by expression of channelrhodopsin. The release of OXT onto CHO cells in the DMNX was blunted in rats exposed to 21 days of CIH/H. Chronic activation of PVN OXT neurons in vivo, using designer receptors exclusively activated by designer drugs, restored the release of OXT onto CHO cells in the DMNX. Chronic PVN OXT neuron activation in vivo also prevented the hypertension that occurred in conscious unrestrained telemetry-equipped sham rats exposed to 3 wk of CIH/H. These results demonstrate that chronic activation of OXT neurons restores the release of OXT from PVN fibers in the DMNX and prevents the hypertension that occurs with 3 wk of CIH/H exposure.
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, DC; Institute for Biomedical Sciences, The George Washington University, Washington, DC;
authors.forename: Heather
authors.initials: H
authors.lastname: Jameson
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, DC;
authors.forename: Ryan
authors.initials: R
authors.lastname: Bateman
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, DC;
authors.forename: Peter
authors.initials: P
authors.lastname: Byrne
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, DC;
authors.forename: Jhansi
authors.initials: J
authors.lastname: Dyavanapalli
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, DC; Institute for Biomedical Sciences, The George Washington University, Washington, DC;
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medicine, The George Washington University, Washington, DC.
authors.forename: Vivek
authors.initials: V
authors.lastname: Jain
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, DC; Institute for Biomedical Sciences, The George Washington University, Washington, DC; dmendel@gwu.edu.
authors.forename: David
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D001794:Blood Pressure; D016466:CHO Cells; D000075402:Channelrhodopsins; D002908:Chronic Disease; D003412:Cricetulus; D004195:Disease Models, Animal; D006935:Hypercapnia / Q000150:complications*; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D062308:Optogenetics; D010121:Oxytocin / Q000235:genetics / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013686:Telemetry; D013997:Time Factors; D014162:Transfection
chemical_list: D000075402:Channelrhodopsins; C569600:OXTR protein, human; D018045:Receptors, Oxytocin; D010121:Oxytocin
keywords: hypoxia; oxytocin; paraventricular nucleus of hypothalamus