title: Chronic intermittent hypoxia alters neurotransmission from lateral paragigantocellular nucleus to parasympathetic cardiac neurons in the brain stem.
abstract: Patients with sleep-related disorders, including obstructive sleep apnea (OSA), have an increased risk of cardiovascular diseases. OSA events are more severe in rapid eye movement (REM) sleep. REM sleep further increases the risk of adverse cardiovascular events by diminishing cardioprotective parasympathetic activity. The mechanisms underlying REM sleep-related reduction in parasympathetic activity likely include activation of inhibitory input to cardiac vagal neurons (CVNs) in the brain stem originating from the lateral paragigantocellular nucleus (LPGi), a nucleus that plays a role in REM sleep control. This study tests the hypothesis that chronic intermittent hypoxia and hypercapnia (CIHH), an animal model of OSA, inhibits CVNs because of exaggeration of the GABAergic pathway from the LPGi to CVNs. GABAergic neurotransmission to CVNs evoked by electrical stimulation of the LPGi was examined with whole cell patch-clamp recordings in an in vitro brain slice preparation in rats exposed to CIHH and control rats. GABAergic synaptic events were enhanced after 4-wk CIHH in both male and female rats, to a greater degree in males. Acute hypoxia and hypercapnia (H/H) reversibly diminished the LPGi-evoked GABAergic neurotransmission to CVNs. However, GABAergic synaptic events were enhanced after acute H/H in CIHH male animals. Orexin-A elicited a reversible inhibition of LPGi-evoked GABAergic currents in control animals but evoked no significant changes in CIHH male rats. In conclusion, exaggerated inhibitory neurotransmission from the LPGi to CVNs in CIHH animals would reduce cardioprotective parasympathetic activity and enhance the risk of adverse cardiovascular events.
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, District of Columbia olgad@gwu.edu.
authors.forename: Olga
authors.initials: O
authors.lastname: Dergacheva
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D053444:Inhibitory Postsynaptic Potentials; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000008:administration & dosage / Q000378:metabolism; D000068797:Orexins; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D020181:Sleep Apnea, Obstructive; D009435:Synaptic Transmission / Q000502:physiology*; D046509:Tissue Culture Techniques; D014630:Vagus Nerve / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D005680:gamma-Aminobutyric Acid
keywords: REM sleep; apnea; brain stem; cardiac vagal neurons; hypercapnia; hypoxia