Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study we investigated the involvement of the hypothalamic paraventricular nucleus (PVN) in the modulation of sympathoexcitatory reflex activated by peripheral and central chemoreceptors. We measured mean arterial blood pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) before and after blocking neurotransmission within the PVN by bilateral microinjection of 2% lidocaine (100 nl) during specific stimulation of peripheral chemoreceptors by potassium cyanide (KCN, 75 microg/kg iv, bolus dose) or stimulation of central chemoreceptors with hypercapnia (10% CO(2)). Typically stimulation of peripheral chemoreceptors evoked a reflex response characterized by an increase in MAP, RSNA, and PNA and a decrease in HR. Bilateral microinjection of 2% lidocaine into the PVN had no effect on basal sympathetic and cardiorespiratory variables; however, the RSNA and PNA responses evoked by peripheral chemoreceptor stimulation were attenuated (P < 0.05). Bilateral microinjection of bicuculline (50 pmol/50 nl, n = 5) into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation (P < 0.05). Conversely, the GABA agonist muscimol (0.2 nmol/50 nl, n = 5) injected into the PVN attenuated these reflex responses (P < 0.05). Blocking neurotransmission within the PVN had no effect on the hypercapnia-induced central chemoreflex responses in carotid body denervated animals. These results suggest a selective role of the PVN in processing the sympathoexcitatory and ventilatory component of the peripheral, but not central, chemoreflex.
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PMID:Differential role of the paraventricular nucleus of the hypothalamus in modulating the sympathoexcitatory component of peripheral and central chemoreflexes. 1610 20

We discuss the influence of astrocytes on respiratory function, particularly central CO2 chemosensitivity. Fluorocitrate (FC) poisons astrocytes, and studies in intact animals using FC provide strong evidence that disrupting astrocytic function can influence CO2 chemosensitivity and ventilation. Gap junctions interconnect astrocytes and contribute to K+ homeostasis in the extracellular fluid (ECF). Blocking gap junctions alters respiratory control, but proof that this is truly an astrocytic effect is lacking. Intracellular pH regulation of astrocytes has reciprocal effects on extracellular pH. Electrogenic sodium-bicarbonate transport (NBCe) is present in astrocytes. The activity of NBCe alkalinizes intracellular pH and acidifies extracellular pH when activated by depolarization (and a subset of astrocytes are depolarized by hypercapnia). Thus, to the extent that astrocytic intracellular pH regulation during hypercapnia lowers extracellular pH, astrocytes will amplify the hypercapnic stimulus and may influence central chemosensitivity. However, the data so far provide only inferential support for this hypothesis. A lactate shuttle from astrocytes to neurons seems to be active in the retrotrapezoid nucleus (RTN) and important in setting the chemosensory stimulus in the RTN (and possibly other chemosensory nuclei). Thus astrocytic processes, so vital in controlling the constituents of the ECF in the central nervous system, may profoundly influence central CO2 chemosensitivity and respiratory control.
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PMID:Glia modulation of the extracellular milieu as a factor in central CO2 chemosensitivity and respiratory control. 2011 May 40

Release of hypocretins (orexins) by neurons in the lateral hypothalamus is an important contributor to arousal state, thermoregulation, feeding behavior, and has recently been proposed to play a role in breathing and central chemosensitivity. Using the in situ arterially perfused juvenile rat preparation, we determined the effect of hypocretin-1 (hcrt-1) and SB-408124 (antagonist for hypocretin receptor subtype 1, hcrt-r1) on phrenic nerve activity, a neural correlate of breathing (neuroventilation), and the neuroventilatory sensitivity to CO(2). Application of hcrt-1 through the perfusate had little effect on baseline firing. Blocking hcrt-r1, however, prevented the phrenic burst frequency response normally associated with hypercapnia. These data suggest that endogenous hypocretinergic modulation enhances neuroventilatory chemosensitivity. Further studies using the in vitro medullary slice preparation explored the effect of hcrt-1 on hypoglossal nerve activity, a correlate of ventilation in vitro. Application of exogenous hcrt-1 failed to significantly alter hypoglossal burst output in neonatal rat slices, indicating that this portion of the neuroventilatory circuit is insensitive to hcrt-1. Taken together, these data suggest that hcrt-1 is a modulator of central chemosensitivity.
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PMID:Modulation of respiratory activity by hypocretin-1 (orexin A) in situ and in vitro. 2021 31