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- W1277776080 abstract "Patients with obstructive sleep apnea (OSA) have an increased risk of cardiovascular diseases and altered plasma levels of orexin. REM sleep further increases the incidence of adverse cardiovascular events. The mechanisms underlying REM sleep-related reduction in parasympathetic activity include activation of inhibitory input to cardiac vagal neurons (CVNs) in the brainstem originating from the lateral paragigantocellular nucleus (LPGi), a nucleus which plays a role in REM sleep control. This study tests the hypotheses that (1) chronic intermittent hypoxia and hypercapnia (CIHH) inhibits CVNs due to exaggeration of GABAergic pathway from the LPGi to CVNs; (2) orexinergic signaling in CVNs is diminished by CIHH; and (3) identified orexin neurons (orexin-EGFP-2A-Cre rat) are inhibited by acute hypoxia/hypercapnia. GABAergic neurotransmission to CVNs evoked by electrical stimulation of the LPGi was examined using whole-cell patch-clamp recordings in rats exposed to CIHH and control rats. GABAergic synaptic events were enhanced following 4 weeks of CIHH. Orexin-A elicited inhibition of LPGi-evoked GABAergic current in control animals but evoked no significant changes in CIHH rats. Acute hypoxia/hypercapnia inhibited the firing activity of orexin neurons and diminished glutamatergic neurotransmission to orexin neurons. In summary, repetitive episodes of hypoxia/hypercapnia would diminish activity of orexin neurons, including the orexinergic neurotransmission to CVNs. Diminished orexinergic signaling, along with exaggerated inhibitory neurotransmission from the LPGi to CVNs would reduce cardio-protective parasympathetic activity and increase risk of cardiovascular diseases. Support: Christian Gillin Research Grant 004GN12 to O.D. and NIH grants HL49965, HL59895 and HL72006 to D.M." @default.
- W1277776080 created "2016-06-24" @default.
- W1277776080 creator A5029190163 @default.
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- W1277776080 date "2015-04-01" @default.
- W1277776080 modified "2023-10-13" @default.
- W1277776080 title "Hypoxia and Hypercapnia Impairs Cardiac Vagal Control: the Role of Orexin" @default.
- W1277776080 doi "https://doi.org/10.1096/fasebj.29.1_supplement.985.1" @default.
- W1277776080 hasPublicationYear "2015" @default.
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