Oxytocin neuron activation prevents hypertension that occurs with chronic intermittent hypoxia/hypercapnia in rats

Autor: Ryan Bateman, Heather Jameson, David Mendelowitz, Vivek Jain, Xin Wang, Peter Byrne, Jhansi Dyavanapalli
Rok vydání: 2016
Předmět:
Male
Time Factors
Physiology
Blood Pressure
Biosensing Techniques
030204 cardiovascular system & hematology
Oxytocin
Hypercapnia
Rats
Sprague-Dawley
0302 clinical medicine
Telemetry
Medicine
Hypoxia
Receptor
Neurons
medicine.anatomical_structure
Receptors
Oxytocin
Hypertension
medicine.symptom
Cardiology and Cardiovascular Medicine
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
medicine.drug
endocrine system
medicine.medical_specialty
Cardiovascular Neurohormonal Regulation
CHO Cells
Optogenetics
Transfection
03 medical and health sciences
Cricetulus
Channelrhodopsins
In vivo
Physiology (medical)
Internal medicine
Animals
business.industry
Hypoxia (medical)
Disease Models
Animal
Dorsal motor nucleus
Endocrinology
nervous system
Paraventricular nucleus of hypothalamus
Chronic Disease
Neuron
business
030217 neurology & neurosurgery
Paraventricular Hypothalamic Nucleus
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 310:H1549-H1557
ISSN: 1522-1539
0363-6135
DOI: 10.1152/ajpheart.00808.2015
Popis: 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.
Databáze: OpenAIRE
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