scholarly journals Chronic Intermittent Hypoxia and Hypercapnia Inhibit the Hypothalamic Paraventricular Nucleus Neurotransmission to Parasympathetic Cardiac Neurons in the Brain Stem

Hypertension ◽  
2014 ◽  
Vol 64 (3) ◽  
pp. 597-603 ◽  
Author(s):  
Olga Dergacheva ◽  
Jhansi Dyavanapalli ◽  
Ramón A. Piñol ◽  
David Mendelowitz
Keyword(s):  
Brain Stem ◽  
Paraventricular Nucleus ◽  
Intermittent Hypoxia ◽  
Hypothalamic Paraventricular Nucleus ◽  
Chronic Intermittent Hypoxia ◽  
The Brain

scholarly journals Chronic intermittent hypoxia increases sympathetic control of blood pressure: role of neuronal activity in the hypothalamic paraventricular nucleus

2013 ◽  
Vol 305 (12) ◽  
pp. H1772-H1780 ◽  
Author(s):  
Amanda L. Sharpe ◽  
Alfredo S. Calderon ◽  
Mary Ann Andrade ◽  
J. Thomas Cunningham ◽  
Steven W. Mifflin ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Neuronal Activity ◽  
Paraventricular Nucleus ◽  
Intermittent Hypoxia ◽  
Body Fluid ◽  
Early Stage ◽  
Brain Regions ◽  
Hypothalamic Paraventricular Nucleus ◽  
Chronic Intermittent Hypoxia ◽  
Increased Sensitivity

Like humans with sleep apnea, rats exposed to chronic intermittent hypoxia (CIH) experience arterial hypoxemias and develop hypertension characterized by exaggerated sympathetic nerve activity (SNA). To gain insights into the poorly understood mechanisms that initiate sleep apnea/CIH-associated hypertension, experiments were performed in rats exposed to CIH for only 7 days. Compared with sham-treated normoxic control rats, CIH-exposed rats ( n = 8 rats/group) had significantly increased hematocrit ( P < 0.001) and mean arterial pressure (MAP; P < 0.05). Blockade of ganglionic transmission caused a significantly ( P < 0.05) greater reduction of MAP in rats exposed to CIH than control rats ( n = 8 rats/group), indicating a greater contribution of SNA in the support of MAP even at this early stage of CIH hypertension. Chemical inhibition of neuronal discharge in the hypothalamic paraventricular nucleus (PVN) (100 pmol muscimol) had no effect on renal SNA but reduced lumbar SNA ( P < 0.005) and MAP ( P < 0.05) more in CIH-exposed rats ( n = 8) than control rats ( n = 7), indicating that CIH increased the contribution of PVN neuronal activity in the support of lumbar SNA and MAP. Because CIH activates brain regions controlling body fluid homeostasis, the effects of internal carotid artery injection of hypertonic saline were tested and determined to increase lumbar SNA more ( P < 0.05) in CIH-exposed rats than in control rats ( n = 9 rats/group). We conclude that neurogenic mechanisms are activated early in the development of CIH hypertension such that elevated MAP relies on increased sympathetic tonus and ongoing PVN neuronal activity. The increased sensitivity of Na+/osmosensitive circuitry in CIH-exposed rats suggests that early neuroadaptive responses among body fluid regulatory neurons could contribute to the initiation of CIH hypertension.

Chronic intermittent hypoxia alters neurotransmission from lateral paragigantocellular nucleus to parasympathetic cardiac neurons in the brain stem

2015 ◽  
Vol 113 (1) ◽  
pp. 380-389 ◽  
Author(s):  
Olga Dergacheva
Keyword(s):  
Brain Stem ◽  
Rem Sleep ◽  
Cardiovascular Events ◽  
Intermittent Hypoxia ◽  
Female Rats ◽  
Parasympathetic Activity ◽  
Male Rats ◽  
Chronic Intermittent Hypoxia ◽  
Gabaergic Neurotransmission ◽  
The Brain

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.

scholarly journals Neuropeptide FF and neuropeptide VF inhibit GABAergic neurotransmission in parvocellular neurons of the rat hypothalamic paraventricular nucleus

2007 ◽  
Vol 292 (5) ◽  
pp. R1872-R1880 ◽  
Author(s):  
Jack H. Jhamandas ◽  
Frédéric Simonin ◽  
Jean-Jacques Bourguignon ◽  
Kim H. Harris
Keyword(s):  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Inhibitory Input ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Gabaergic Neurotransmission ◽  
Whole Cell Patch Clamp ◽  
Neuropeptide Ff ◽  
Parvocellular Neurons ◽  
The Brain

Neuropeptide FF (NPFF) and neuropeptide VF (NPVF) are octapeptides belonging to the RFamide family of peptides that have been implicated in a wide variety of physiological functions in the brain, including central autonomic and neuroendocrine regulation. The effects of these peptides are mediated via NPFF1 and NPFF2 receptors that are abundantly expressed in the rat brain, including the hypothalamic paraventricular nucleus (PVN), an autonomic nucleus critical for the secretion of neurohormones and the regulation of sympathetic outflow. In this study, we examined, using whole cell patch-clamp recordings in the brain slice, the effects of NPFF and NPVF on inhibitory GABAergic synaptic input to parvocellular PVN neurons. Under voltage-clamp conditions, NPFF and NPVF reversibly and in a concentration-dependent manner reduced the evoked bicuculline-sensitive inhibitory postsynaptic currents (IPSCs) in parvocellular PVN neurons by 25 and 31%, respectively. RF9, a potent and selective NPFF receptor antagonist, blocked NPFF-induced reduction of IPSCs. Recordings of miniature IPSCs in these neurons following NPFF and NPVF applications showed a reduction in frequency but not amplitude, indicating a presynaptic locus of action for these peptides. Under current-clamp conditions, NPVF and NPFF caused depolarization (6–9 mV) of neurons that persisted in the presence of TTX but was abolished in the presence of bicuculline. Collectively, these data provide evidence for a disinhibitory role of NPFF and NPVF in the hypothalamic PVN via an attenuation of GABAergic inhibitory input to parvocellular neurons of this nucleus and explain the central autonomic effects of NPFF.

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