title: Chronic intermittent hypoxia and hypercapnia inhibit the hypothalamic paraventricular nucleus neurotransmission to parasympathetic cardiac neurons in the brain stem.
abstract: Obstructive sleep apnea is associated with chronic intermittent hypoxia/hypercapnia (CIHH) episodes during sleep that heighten sympathetic and diminish parasympathetic activity to the heart. Although one population of neurons in the paraventricular nucleus of the hypothalamus strongly influences sympathetic tone and has increased activity after CIHH, little is known about the role of this pathway to parasympathetic neurons and how this network is altered in CIHH. We hypothesized that CIHH inhibits the excitatory pathway from the paraventricular nucleus of the hypothalamus to parasympathetic cardiac vagal neurons in the brain stem. To test this hypothesis, channelrhodopsin was selectively expressed, using viral vectors, in neurons in the paraventricular nucleus of the hypothalamus and channelrhodopsin-expressing fibers were photoactivated to evoke postsynaptic currents in cardiac vagal neurons in brain stem slices. Excitatory postsynaptic currents were diminished in animals exposed to CIHH. The paired-pulse and prolonged facilitation of the postsynaptic current amplitudes and frequencies evoked by paired and bursts of photoactivation of channelrhodopsin fibers, respectively, occurred in unexposed rats but were blunted in CIHH animals. In response to an acute challenge of hypoxia/hypercapnia, the amplitude of postsynaptic events was unchanged during, but increased after hypoxia/hypercapnia in unexposed animals. In contrast, postsynaptic currents were inhibited during hypoxia/hypercapnia in rats exposed to CIHH. In conclusion, the excitatory pathway to cardiac vagal neurons is diminished in response to both acute and chronic exposures to hypoxia/hypercapnia. This could elicit a reduced cardioprotective parasympathetic activity and an enhanced risk of adverse cardiovascular events in episodes of apnea and chronic obstructive sleep apnea.
authors: From the Department of Pharmacology and Physiology, Department of Anesthesiology and Critical Care Medicine, The George Washington University, Washington, DC.
authors: Olga
authors: O
authors: Dergacheva
authors: From the Department of Pharmacology and Physiology, Department of Anesthesiology and Critical Care Medicine, The George Washington University, Washington, DC.
authors: Jhansi
authors: J
authors: Dyavanapalli
authors: From the Department of Pharmacology and Physiology, Department of Anesthesiology and Critical Care Medicine, The George Washington University, Washington, DC.
authors: Ramón A
authors: RA
authors: Piñol
authors: From the Department of Pharmacology and Physiology, Department of Anesthesiology and Critical Care Medicine, The George Washington University, Washington, DC. dmendel@gwu.edu.
authors: David
authors: D
authors: Mendelowitz
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000294:innervation*; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000503:physiopathology*; D010286:Paraventricular Hypothalamic Nucleus / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins
keywords: anoxia; hypercapnia; hypothalamus