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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have demonstrated that suprapontine areas of the brain modulate the respiratory responses to hypoxia and hypercapnia. The purpose of the present study was to determine if neurons in the posterior hypothalamus are responsible for this modulation. The respiratory (monitored from diaphragmatic activity) and cardiovascular responses to hypoxia and to hypercapnia were examined in anesthetized rats before and after microinjection of a GABA synthesis inhibitor (3-mercaptopropionic acid, 3-MP) into the posterior hypothalamus. Unilateral micro-injection of 3-MP into the posterior hypothalamus elicited an increase in minute diaphragmatic activity (+54.9 +/- 15.8%), arterial pressure (10.5 +/- 3.2 mmHg) and heart rate (26.8 +/- 10.7 min-1) after a delay of 15-20 minutes. The respiratory responses to hypercapnia but not the cardiovascular responses were greatly accentuated after hypothalamic microinjections of 3-mercaptopropionic acid. In contrast, none of the responses (increases in diaphragmatic activity and heart rate; fall in arterial pressure) elicited by hypoxia were altered after microinjections of the GABA synthesis inhibitor into the posterior hypothalamus. These findings indicate that a GABAergic inhibition of posterior hypothalamic neurons modulates the respiratory response to hypercapnia.
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PMID:Hypothalamic GABAergic mechanism involved in respiratory response to hypercapnia. 154 Aug 37

During moderate hypercapnia, spectrum analysis of efferent phrenic nerve activity (PNA) of urethane anesthetized rabbits revealed high-frequency oscillations (HFO). The spectral peak (mean frequency 111 Hz) was reversibly eliminated by the glycine receptor antagonist strychnine administered into the 4th cerebral ventricle. In contrast, blockade of brainstem GABAA receptors by bicuculline did not abolish HFO but even reinforced or induced HFO. Thus, there is evidence that fast synaptic inhibition via glycine receptors is involved in the generation of HFO within the medullary respiratory center, whereas GABA may play a modulatory role.
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PMID:Involvement of fast synaptic inhibition in the generation of high-frequency oscillation in central respiratory system. 272 Apr 1

gamma-Aminobutyric acid (GABA) content of the brain increases during hypoxia and hypercapnia and GABA by itself is a central ventilatory depressant and may depress metabolism as well. Therefore the effect of centrally administered GABA by ventriculocisternal perfusion on O2 consumption (VO2) and CO2 production (VCO2) was studied in pentobarbital-anesthetized dogs. GABA (30 mM) in mock cerebrospinal fluid (CSF) was perfused for 15 min at the rate of 1.0 ml/min followed by perfusion with mock CSF alone. Body temperature, perfusion pressure, and CSF pH were kept constant. Minute ventilation (VE) was kept constant mechanically. Under these conditions, VO2, VCO2, alveolar ventilation (VA), and relative pulmonary dead space volume (VD/VT) were measured. During perfusion with 30 mM GABA, mean VO2 (+/- SE) decreased from 96.5 +/- 3.3 to 81.9 +/- 5.1 ml/min, VCO2 from 72.1 +/- 3.8 to 60.7 +/- 3.0 ml/min, and VA from 1.7 +/- 0.1 to 1.3 +/- 0.1 l/min. VD/VT increased from 0.55 +/- 0.02 to 0.65 +/- 0.01. Perfusion with mock CSF alone restored these parameters to initial levels within 15 min. We conclude that centrally administered GABA depresses VO2 and VCO2. This reduction in metabolic function is independent of the central modulatory effects of GABA on respiration.
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PMID:Effect of centrally administered gamma-aminobutyric acid on metabolic function. 309 66

The intrinsic processes involved in the initiation and arrest of seizures are not completely understood. Cortical and cerebellar inhibitory mechanisms, accumulation of metabolic products, and glial uptake of extracellular potassium (K+o), anions, and released neurotransmitters are all important processes that limit focal firing and terminate a seizure once it has been initiated. Of these, the intrinsic cortical inhibitory mechanisms--i.e., recurrent and surround inhibition--appear to be the most important. Active cation and anion transport processes are two metabolic events that have yet to be elucidated but clearly could be involved in terminating a seizure discharge. For example, without an active mechanism to transport chloride, opening of the chloride channel by the inhibitory transmitter GABA would not result in increased chloride permeability. The transient hypoxia and hypercapnia and lactic acidosis that follows a severe tonic-clonic seizure produces a mixed systemic metabolic and respiratory acidosis. In experimental animals, the hypercapnia that results is sufficient to block seizure discharges. Increasing the CO2 concentration significantly reduces the extension to flexion (E/F) ratio of mice given maximal electroshock seizures (MES) and increases the time required for 50% of the animals to recover sufficiently from a first MES to be able to have another MES. The decreased E/F ratio and the increased recovery time (RT50) are both indicative of a decrease in seizure activity. Since the extent to which CO2 is allowed to accumulate in the brain is regulated by the glial specific enzyme carbonic anhydrase (CA), it follows that the glial cell has an integral role in the mechanisms involved in arresting seizure activity. In contrast, hypoxia increased the E/F ratio and decreased the RT50, evidence that seizure activity was enhanced. Another metabolic factor affecting duration of seizure activity, susceptibility to seizures, and recovery from seizures is glucose. Recovery from seizures depends in part on an adequate supply of this energy source. An inverse correlation (R = 0.95) between RT50 and blood sugar was found when the blood sugar was altered experimentally by treatments that altered the endocrine status (pancreatectomy, treatment with alloxan, cortisol, insulin, glucagon, and dextrose). Since glial cells contain (as glycogen) the small amount of glucose present in the brain, they probably hasten the ability of the brain to recover normal function following a seizure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of glial cation and anion transport mechanisms in etiology and arrest of seizures. 370 23

The purpose of this study was to measure changes in local cerebral blood flow (1-CBF) during generalized seizures, and to study whether or not formation of prostaglandins or related substances contributes to the increased flow rates. Seizures were induced in ventilated rats maintained on 70% N2O and 30% O2 by the i.v. injection of the GABA receptor blocker bicuculline (1.2 mg . kg-1). Formation of prostaglandins was inhibited by the administration of the fatty acid cyclo-oxygenase inhibitor indomethacin (10 mg . kg-1). Local CBF in 21 defined brain structures was measured autoradiographically with 14C-iodoantipyrine as the diffusible tracer. After 20 min of continuous seizure activity 1-CBF increased 1.5--5-fold, the smallest increases (less than 200% of control) being observed in frontal and auditory cortex and in the caudoputamen, and the largest (greater than 400% of control) in substantia nigra, thalamus, visual cortex, lateral geniculate and hypothalamus. In general, the largest increases in 1-CBF occurred in sensory and limbic systems (and hypothalamus) while motor systems showed a pronounced variability. In the majority of structures examined indomethacin failed to modify the CBF response during seizures. Although this result suggests that seizures, in contrast to hypercapnia, lead to an increased CBF by other mechanisms than those related to prostaglandin formation, some structures (nucleus ruber, cerebellum, and superior colliculus) showed a clearly reduced 1-CBF in indomethacin-treated animals.
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PMID:Local cerebral blood flow in the brain during bicuculline-induced seizures and the modulating influence of inhibition of prostaglandin synthesis. 728 97

Activation of the cerebellar parallel fibers (PF) releases glutamate and leads to depolarization of Purkinje cells and interneurons. These cells, in turn, release GABA. We have studied the role of glutamate, GABA, nitric oxide (NO) and adenosine in the increases in cerebellar cortex blood flow (BFcrb) elicited by PF stimulation. In anesthetized rats (halothane 1%) the cerebellar vermis was exposed and the site was superfused with Ringer (37 degrees C, pH 7.4). The PF were stimulated electrically (50-100 microA; 30 Hz) and the increases in BFcrb were recorded using a laser-Doppler flowmeter. Field potentials were recorded using glass microelectrodes. During Ringer superfusion, PF stimulation increased BFcrb by 58 +/- 5% (P < 0.001; analysis of variance; n = 6). Superfusion with the broad spectrum glutamate receptor antagonist kynurenic acid (Kyn; 5 mM) abolished the negative component of the field potential (n = 4), a finding reflecting lack of depolarization of Purkinje cells and interneurons, and blocked the increase in BFcrb (P > 0.05 from Ringer; n = 6). In contrast, Kyn did not influence the increase in BFcrb evoked by hypercapnia (pCO2 55.4 +/- 1.1 mmHg) or by superfusion with the NO donor SIN-1 (0.1, 1 mM; P > 0.05; n = 6). Superfusion with the adenosine receptor antagonist 8-sulphophenyltheophylline (8-SPT; 100 microM) reduced the elevation in BFcrb by 45 +/- 4% (P < 0.05; n = 6) and co-application of 8-SPT and of the NO synthase inhibitor nitro-L-arginine (L-NA; 1 mM) attenuated the vasodilation further (-82 +/- 4% from Ringer; P < 0.01 from 8-SPT alone).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide and adenosine mediate vasodilation during functional activation in cerebellar cortex. 753 29

We studied the formation of vasomotor reflexes in hypokinesia and responses of the brain vessels to the action of GABA, hypotension, and hypercapnia. We found that the response of the brain vessels to GABA is delayed and the mechanisms which supported an adequate cerebral vasculation are distorted in hypotension. At the same time the disturbance of the reflectory reaction of the brain vessels in the course of forming the vasomotor reflexes and the absence of significant changes in response to GABA were noticed. The capability of GABA of inhibiting cerebral blood circulation arising in hypokinesia is shown.
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PMID:[The cerebral blood circulation during hypokinesia under the influence of hypercapnia, hypotonia, GABA and neurosensory stimulation]. 758 Jul 46

Prior results from this laboratory have demonstrated that the respiratory response to hypercapnia is enhanced by microinjection of GABA antagonists or GABA synthesis inhibitors into the caudal hypothalamus of both cats and rats. However, no evidence was found for modulation of the respiratory response to hypoxia by a hypothalamic GABAergic mechanism. The purpose of the present study was to determine if synaptic input other than GABAergic onto caudal hypothalamic neurons affects the respiratory responses to hypoxia. The respiratory (diaphragmatic EMG) responses to hypoxia (10% O2) and hypercapnia (5% CO2) were recorded in anesthetized rats before and after bilateral microinjection of a blocker of synaptic transmission (CoCl2, 100 mM) or an excitatory amino acid receptor antagonist (kynurenic acid, 50 mM) into the caudal hypothalamus. Both hypoxia and hypercapnia elicited increases in tidal diaphragmatic activity and respiratory frequency prior to the microinjections. The respiratory response to hypercapnia was increased (+10.5%) after CoCl2 microinjections, which is consistent with prior results obtained with blockade of GABAergic input. Kynurenic acid did not alter the respiratory response to hypercapnia. A new finding was that the respiratory response to hypoxia was diminished after both CoCl2 (-13.0%) and kynurenic acid (-25.0%) microinjections. The results of this study support our prior findings that neurons in the caudal hypothalamus modulate the respiratory response to hypercapnia. In addition, our findings suggest that an excitatory input acting through excitatory amino acid receptors in the caudal hypothalamus modulates the respiratory responses to hypoxia.
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PMID:Modulation of the respiratory responses to hypoxia and hypercapnia by synaptic input onto caudal hypothalamic neurons. 789 38

Premature infants respond to hypercapnia by an attenuated ventilatory response that is characterized by a decrease in respiratory frequency. We hypothesized that this impaired hypercapnic ventilatory response is of central origin and is mediated via gamma-aminobutyric acid-ergic (GABAergic) pathways. We therefore studied two groups of maturing Sprague-Dawley rats: unrestrained rats in a whole body plethysmograph at four postnatal ages (5, 16-17, 22-23, and 41-42 days); and ventilated, decerebrate, vagotomized, paralyzed rats in which phrenic nerve responses to hypercapnia were measured at 4-6 and 37-39 days of age. In the unrestrained group, the increase in minute ventilation induced by hypercapnia was significantly lower at 5 days vs. beyond 16 days. Although there was an increase in tidal volume at all ages, frequency decreased significantly from baseline at 5 days, whereas it increased significantly at 16-17, 22-23, and 41-42 days. The decrease in frequency at 5 days of age was mainly due to a significant prolongation in expiratory duration (TE). In the ventilated group, hypercapnia also caused prolongation in TE at 4-6 days but not at 37-39 days of age. Intravenous administration of bicuculline (GABA(A)-receptor blocker) abolished the prolongation of TE in response to hypercapnia in the newborn rats. We conclude that newborn rat pups exhibit a characteristic ventilatory response to CO(2) expressed as a centrally mediated prolongation of TE that appears to be mediated by GABAergic mechanisms.
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PMID:Changes in respiratory timing induced by hypercapnia in maturing rats. 1044 2

In these studies, we determined the contribution of central mechanisms and the role of GABA(A)-receptor signal transduction pathways in mediating hypercapnia-induced slowing of breathing frequency. Experiments were performed in decerebrate, vagotomized, paralyzed and mechanically ventilated piglets of 3-5 days and 2-3 weeks of age (n=19). Repeated exposure to progressive hyperoxic hypercapnia induced a reproducible increase in phrenic nerve activity, accompanied by a CO2 concentration-dependent increase in expiratory duration. No differences were observed in piglets with intact or cut carotid sinus nerves. Intravenous administration of bicuculline (2 mg/kg: n=7), a gamma-aminobutyric acid (GABA(A)) receptor antagonist, significantly reduced the CO2-induced prolongation of TE. These data demonstrate for the first time that in early postnatal life, hypercapnia induced increase in phrenic activity is associated with centrally mediated prolongation of expiratory duration. Furthermore. the results suggest that brainstem GABAergic mechanisms play an important role in CO2-induced prolongation of expiratory time during early development.
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PMID:CO2-induced prolongation of expiratory time during early development. 1048 98


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