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)

Adenosine-5'-carboxylic acid-amide (1 mug/kg/min) and adenosine (500 mug/kg/min), given in a 10-min infusion to anaesthetized dogs, produced qualitatively and quantitatively comparable cardiovascular effects, namely a marked increase in coronary blood flow and a generalized vasodilation, concomitantly with an increase in heart rate, left ventricular dp/dt, heart work, myocardial oxygen consumption, and pulmonary blood pressure; the pulmonary vascular resistance remained unchanged. Hypercapnic acidosis enhanced the coronary dilator effect of both compounds. These results indicate that adenosine and adenosine-5'-carboxylic acid-amide act at the same receptor sites.
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PMID:Haemodynamic effects of adenosine-5'-carboxylic acid-amide in the anaesthetized dog during normal respiration and hypercapnic acidosis. 126 38

Intravenously administered adenosine may increase ventilation (VI) and the ventilatory response to CO2 (HCVR). Inasmuch as we have previously hypothesized that those with higher HCVR may be more prone to periodic breathing during sleep, we measured VI and HCVR and monitored ventilatory pattern in seven healthy subjects before and during an infusion of adenosine (80 micrograms.kg-1.min-1) during uninterrupted sleep. Adenosine increased the mean sleeping VI (7.6 +/- 0.4 vs. 6.5 +/- 0.4 l/min, P less than 0.05) and decreased mean end-tidal CO2 values (42.4 +/- 1.2 vs. 43.7 +/- 1.0 Torr, P = 0.06, paired t test) during stable breathing. In six of seven subjects, periodic breathing occurred during this infusion. The amplitude (maximum VI--mean VI) and period length of this periodic breathing was variable among subjects and not predicted by baseline HCVR [correlation coefficients (r) = 0.64, P = 0.17 and r = -0.1, P = 0.9, respectively]. Attempts to measure HCVR during adenosine infusion were unsuccessful because of frequent arousals and continued periodic breathing despite hyperoxic hypercapnia. We conclude that adenosine infusion increases VI and produces periodic breathing during sleep in most normal subjects studied.
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PMID:Adenosine infusion and periodic breathing during sleep. 156 53

Adenosine has been proposed as a metabolic factor involved in the regulation of cerebral blood flow. The evidence in support of this hypothesis, presented in this review, includes information on the adenosine receptors associated with cerebral blood vessels, the synthesis and metabolism of adenosine, and the release of adenosine from the brain. Adenosine dilates cerebral blood vessels, acting at an A2 receptor. The critical evidence implicating an involvement of adenosine in cerebrovascular regulation is derived from experiments with adenosine antagonists and potentiators. The antagonists include methylxanthine adenosine receptor antagonists and the enzyme adenosine deaminase. Potentiators include transport inhibitors, enzyme inhibitors, and adenosine precursors. Adenosine has been implicated in vascular regulation during hypoxia/ischemia, hypercapnia, seizures, severe hypotension, and hypoglycemia. Adenosine possesses a number of properties that can be used to minimize neuronal degeneration during cerebral insults, such as ischemia, including vasodilatation, reduction of excitatory transmitter release, reduction of membrane calcium permeability, inhibition of platelets, and neutrophil aggregation. Several recent studies have demonstrated that manipulation of central adenosine tone can alter the extent of cerebral ischemic damage, indicating a potential new therapeutic approach for the treatment of stroke.
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PMID:Adenosine in the control of the cerebral circulation. 270 69

Adenosine infusion (100 micrograms X kg-1 X min-1) in humans stimulates ventilation but also causes abdominal and chest discomfort. To exclude the effects of symptoms and to differentiate between a central and peripheral site of action, we measured the effect of adenosine infused at a level (70-80 micrograms X kg-1 X min-1) below the threshold for symptoms. Resting ventilation (VE) and progressive ventilatory responses to isocapnic hypoxia and hyperoxic hypercapnia were measured in six normal men. Compared with a control saline infusion given single blind on the same day, adenosine stimulated VE [mean increase: 1.3 +/- 0.8 (SD) l/min; P less than 0.02], lowered resting end-tidal PCO2 (PETCO2) (mean fall: -3.9 +/- 0.9 Torr), and increased heart rate (mean increase: 16.1 +/- 8.1 beats/min) without changing systemic blood pressure. Adenosine increased the hypoxic ventilatory response (control: -0.68 +/- 0.4 l X min-1 X %SaO2-1, where %SaO2 is percent of arterial O2 saturation; adenosine: -2.40 +/- 1.2 l X min-1 X %SaO2-1; P less than 0.01) measured at a mean PETCO2 of 38.3 +/- 0.6 Torr but did not alter the hypercapnic response. This differential effect suggests that adenosine may stimulate ventilation by a peripheral rather than a central action and therefore may be involved in the mechanism of peripheral chemoreception.
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PMID:Effects of adenosine on ventilatory responses to hypoxia and hypercapnia in humans. 378 85

Hog carotid artery media was incubated under conditions of normocapnia (95% O2-5% CO2) and hypercapnia (nominally 75% O2-25%CO2). The intracellular pH (pHi) was determined from the distribution of 14C-labeled 5,5-dimethyloxazoladine-2,4-dione, alpha- and beta-receptor antagonists were used to block the effects of endogenous catecholamines. With 5% CO2, adenosine had no effect on the pHi. High K+ (25mM) and dipyridamole (DPM) induced a cellular metabolic acidosis that was reversed by adenosine and not affected by 0.5 mM ca2+ or ouabain. Hypercapnia decreased the resting pHi from 7.30 to 6.79. Adenosine significantly attenuated this decrease. With high K+ or DPM, a similar degree of hypercapnia only depressed the pHi to 6.91 and 6.90, respectively. The alkalinizing effect of high K+ and DPM was not altered by 0.5 mM Ca2+, was partically reversed by ouabain, and was completely reversed by adenosine. These results suggest that, under normocapnic conditions, although adenosine relaxes the contraction associated with K+-depolarization, it does not do so by elevating cellular proton levels. However, adenosine may decrease a tissue's ability to attenuate a local respiratory acidosis characteristic of increased O2 demand, resulting in relaxation under hypercapnic conditions. In any case, this demonstrates an interaction, with respect to the acid-base state of the vascular smooth muscle cells, among adenosine, K+, and H+, all suggested components of the metabolic theory of blood flow autoregulation.
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PMID:Adenosine and the acid-base state of vascular smooth muscle. 679 Apr 98

We used the open-chest, anesthetized dog to investigate the possible influence of blood PCO2 on alpha-adrenergic constriction (ansa subclavia stimulation) of previously dilated (adenosine infusion into the left anterior descendens LAD) coronary vessels. During hypercapnia, LAD flow was increased to a significantly greater degree by adenosine than during normocapnia. Adenosine infusion during hypocapnia was least effective in dilating the coronary vasculature. Ansa stimulation at the peak of the adenosine response attenuated LAD flow by 7 and 33 percent respectively during hypo- and hypercapnia. Although there was a significant effect of PCO2 on the vascular response to adenosine, the ability of the adrenergic nerves to attenuate this response in the presence of an altered PCO2 seemed to relate to this pre-existing level of coronary tone.
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PMID:Adenosine coronary vasodilation and sympathetic adrenergic vasoconstriction during altered PCO2. 681 34

Involvement of neurotransmitters in metabolic depression under hypoxia and hypercapnia was examined in Sipunculus nudus. Concentration changes of several putative neurotransmitters in nervous tissue during anoxic or hypercapnic exposure or during combined anoxia and hypercapnia were determined. Among amino acids (gamma-aminobutyric acid, glutamate, glycine, taurine, serine, and aspartate) and monoamines (serotonin, dopamine, and norepinephrine), some changes were significant, but none were consistent with metabolic depression under all experimental conditions applied. Only the neuromodulator adenosine displayed concentration changes in accordance with metabolic depression under all experimental conditions. Levels increased during anoxia, during hypercapnia, and to an even greater extent during anoxic hypercapnia. Adenosine infusions into coelomic fluid via an indwelling catheter induced a significant depression of the normocapnic rate of O2 consumption from 0.36 +/- 0.04 to a minimum of 0.24 +/- 0.02 (SE) mumol.g-1.h-1 after 90 min (n = 6). Application of the adenosine antagonist theophylline caused a transient rise in O2 consumption 30 min after infusion during hypercapnia but not during normocapnia. Effects of adenosine and theophylline were observed in intact individuals but not in isolated body wall musculature. The results provide evidence for a role of adenosine in inducing metabolic depression in S. nudus, probably through the established effects of decreasing neuronal excitability and neurotransmitter release. In consideration of our previous finding that metabolic depression in isolated body wall musculature was elicited by extracellular acidosis, it is concluded that central and cellular mechanisms combine to contribute to the overall reduction in metabolic rate in S. nudus.
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PMID:A role for adenosine in metabolic depression in the marine invertebrate Sipunculus nudus. 903 28

Adenosine is one of the most important neuromodulators in the CNS, both under physiological and pathological conditions. In the isolated spinal cord of the neonatal rat in vitro, acute hypercapnic acidosis (20% CO2, pH 6.7) reversibly depressed electrically evoked spinal reflex potentials. This depression was partially reversed by 8-cyclopentlyl-1,3-dimethylxanthine (CPT), a selective A1 adenosine receptor antagonist. Isohydric hypercapnia (20% CO2, pH 7.3), but not isocapnic acidosis (5% CO2, pH 6.7), depressed the reflex potentials, which were also reversed by CPT. An ecto-5'-nucleotidase inhibitor did not affect the hypercapnic acidosis-evoked depression. An inhibitor of adenosine kinase, but not deaminase, mimicked the inhibitory effect of hypercapnic acidosis on the spinal reflex potentials. Accumulation of extracellular adenosine and inhibition of adenosine kinase activity were caused by hypercapnic acidosis and isohydric hypercapnia, but not isohydric acidosis. These results indicate that the activation of adenosine A1 receptors is involved in the hypercapnia-evoked depression of reflex potentials in the isolated spinal cord of the neonatal rat. The inhibition of adenosine kinase activity is suggested to cause the accumulation of extracellular adenosine during hypercapnia.
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PMID:Involvement of adenosine in depression of synaptic transmission during hypercapnia in isolated spinal cord of neonatal rats. 1677 47

Adenosine is one of the key neurotransmitters involved in hypoxic signaling in the carotid body (CB), and it was recently found to have a modulatory role in mediating hypercapnic sensitivity in the CB. Herein we have investigated the contribution of adenosine to the hypercapnic response in the rat CB and studied the adenosine receptors responsible for this effect. Experiments were performed in Wistar rats. Adenosine release in normoxia (21% O2) and in response to hypercapnia (10% CO2) was quantified by HPLC. Carotid sinus nerve (CSN) chemosensory activity was evaluated in response to hypercapnia in the absence and presence of ZM241385 (300 nM), an A2 antagonist, and SCH58261 (20 nM), a selective A2A antagonist. Hypercapnia increased the extracellular concentrations of adenosine by 50.01%. Both, ZM241385 and SCH58261, did not modify significantly the basal frequency of discharges of the CSN. Also, ZM241385 and SCH58261 did not modify the latency time and the time to peak in CSN chemosensory activity. CSN activity evoked by hypercapnia decreased by 58.82 and 33.59% in response to ZM241385 and to SCH58261, respectively. In conclusion, the effect of adenosine in mediating the hypercapnic response in the rat CB involves an effect on A2A and A2B adenosine receptors.
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PMID:Adenosine Mediates Hypercapnic Response in the Rat Carotid Body via A2A and A2B Receptors. 3035 38