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

Sympathoadrenal activity was studied in 13 young piglets during hypoxia. The piglets were anaesthetized with chloralose/urethane, tracheostomized, paralyzed with gallamine and artificially ventilated. A femoral artery catheter was inserted and used for blood sampling. The piglets were challenged with 6 min of 6% CO2, 10 min of 12% O2 and 6 min of 6% O2 before and after theophylline (an adenosine receptor antagonist) treatment 20 mg/kg (n = 9) or saline (n = 4). Plasma samples were obtained before, during and after each hypercapnic or hypoxic period and analysed for their content of noradrenaline, adrenaline and neuropeptide Y. Hypercapnia with 6% CO2 and moderate hypoxia with 12% O2 did not lead to any significant increase of either noradrenaline (NA), adrenaline (A) or neuropeptide Y (NPY). However, severe hypoxia with 6% O2 increased the NA level from 30 to 66 nmol/l; the A level from 1 to 28 nmol/l and NPY from 140 to 213 pmol/l. After treatment with theophylline the baseline NA increased from 27 to 40 nmol/l, A rom 1.5 to 4.0 and NPY concentration from 65 to 171 pmol/l. Theophylline moderately enhanced the release of NPY, NA and A during the 12% O2 challenge. However, during the severe hypoxia (6%), the increase of NA (from 49 to 333 nmol/l), A (from 8 to 214 nmol/l) and NPY (from 184 to 385 pmol/l) showed considerably enhancement after the theophylline treatment. The results obtained before and after saline were similar showing that the duration of the experiments per se did not change the baseline levels or the effect of the challenges on NA, A or NPY levels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Neuropeptide Y and catecholamine release in the piglet during hypoxia: enhancement by theophylline. 130 59

The effect of local administration of vasodilative concentrations of the adenosine receptor agonist 2-chloroadenosine (2-CADO) on the hyperemic responses of the pial and parenchymal microcirculations to graded hypercapnia was determined. The cranial window and brain microdialysis-hydrogen clearance techniques were utilized in two groups of isoflurane-anesthetized newborn pigs to measure changes in pial diameters and local CBF, respectively, in response to graded hypercapnia in the absence and presence of 2-CADO. Progressive size-dependent dilations of pial arterioles [small = 41 +/- 7 microns (mean +/- SD), intermediate = 78 +/- 13 microns, and large = 176 +/- 57 microns in diameter] occurred in response to graded hypercapnia alone (PaCO2 = 58 and 98 mm Hg) and to superfusions of 2-CADO (10(-5) M) during normocapnia; the magnitude of the dilative response to each of these stimuli was inversely proportional to vessel size. When hypercapnia was induced concomitantly with 2-CADO superfusion, the dilative effects of each stimulus were directly additive. Similarly, local microdialysis infusion of 10(-5) M 2-CADO, which doubled CBF during normocapnia, did not affect the hyperemic response of the parenchymal circulation to graded hypercapnia (PaCO2 = 69 and 101 mm Hg). Our findings are consistent with the participation of adenosine in the mediation of cerebral hypercapnic hyperemia. If, however, adenosine is not involved in this dilative response, our results indicate that concomitant vascular and neuromodulatory actions induced by adenosine receptor stimulation do not affect the mechanism responsible for the hypercapnic hyperemic response.
 ...
PMID:Effect of 2-chloroadenosine on cerebrovascular reactivity to hypercapnia in newborn pig. 161 43

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.
 ...
PMID:Adenosine in the control of the cerebral circulation. 270 69

Variations of arterial PCO2 and pH are known to influence myocardial blood flow (MBF) in that hypercapnia results in a coronary vasodilatation, while hypocapnia possibly decreases MBF. The present study was performed to examine if hypocapnia and hypercapnia might influence the sensitivity to exogenous administration of adenosine. Aminophylline, an adenosine receptor blocking agent, was administered to rule out the effect of endogenously liberated adenosine during variations of PCO2 and pH. In the last part of the study, it was examined whether verapamil, a calcium-channel blocker, might influence the MBF response to variations in PCO2 and pH. Closed-chest dogs were anaesthetized with pentobarbital, and hypocapnia induced by hyperventilation. Carbon dioxide was added to the inspiratory gas to create normocapnia and hypercapnia. In the control group hypocapnia did not significantly reduce MBF although a decrease in coronary sinus (CS) SO2 indicated a coronary vasoconstriction. During continuous adenosine infusion (7.5 +/- 0.3 mg/kg/h) which increased MBF 116% during normocapnia, creating hypocapnia caused a 40% decrease in MBF. Hypercapnia seemed to potentiate the vasodilating effect of adenosine. During administration of aminophylline hypocapnia did not cause any decrease in MBF, while hypercapnia increased MBF by 39%, and these results are in harmony with the results obtained in the control group without aminophylline. Verapamil did not result in any altered MBF response to hypocapnia and hypercapnia when compared to the unblocked control group. These observations do not support the idea of any major influence of the Ca2+ fluxes blocked by verapamil as the cause of MBF changes during variations in PCO2 and pH.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Adenosine modifies canine myocardial blood flow response to hypocapnia and hypercapnia, while aminophylline and verapamil do not. 312 Mar 3

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)
 ...
PMID:Nitric oxide and adenosine mediate vasodilation during functional activation in cerebellar cortex. 753 29

Episodes of hypoxia often occur in hypoglycemic newborns, but it is not known whether dysfunctions in cerebrovascular regulation contribute to brain injury incurred by these affected neonates. We tested the hypotheses that 1) perinatal hypoglycemia impairs cerebrovascular responses to hypoxia and 2) a reduced vascular smooth muscle sensitivity to adenosine accounts for this impairment. Responses of 25- to 50-mu m-diam pial arterioles were determined using the cranial window technique in isoflurane-anesthetized newborn piglets < 5 days of age. Hypoxia (arterial PO2 = 28 +/- 1 mmHg) caused a 47 +/- 5% increase (P = 0.0008) in arteriolar diameter, 89% of which could be blocked by prior superfusion of the window space with the preferential A2-adenosine receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX; 50 microM). Insulin-induced hypoglycemia (blood glucose = 18 +/- 1 mg/dl without isoelectric electroencephalogram) caused a 31 +/- 5% increase (P = 0.002) in arteriolar diameter; however, no additional dilatative response to hypoxia (arterial PO2 = 28 +/- 1 mmHg) could be elicited in these animals. Arteriolar dilation of 41 +/- 6% (P = 0.002) induced by superfusion of 20 microM adenosine under normoglycemic conditions was also completely abolished after the animals were rendered hypoglycemic. Unlike the response to hypoxia and adenosine, hypoglycemia only attenuated prostanoid-dependent dilations to hypercapnia (arterial PCO2 = 68 +/- 3 mmHg) by 55 +/- 9%. These results indicate that, in the newborn, hypoglycemia selectively abolishes hypoxic reactivity through an impairment in adenosine-mediated cerebrovascular dilation.
 ...
PMID:Hypoglycemia selectively abolishes hypoxic reactivity of pial arterioles in piglets: role of adenosine. 786 14

Caffeine is an adenosine receptor antagonist commonly used as a respiratory stimulant to treat neonatal apneas of premature newborn. Neonatal caffeine treatment (NCT) has long-term effects on adenosine receptor expression and distribution; however, the potential effects of NCT on respiratory control development are unknown. To address this issue, rat pups received orally each day from postnatal d 3-12, 15 mg/kg of caffeine (NCT), water (vehicle), or were undisturbed during early life (control). Measurements of resting ventilation, apnea index, and ventilatory response to moderate hypercapnia (FiCO2 = 0.05) were made using whole-body plethysmography at postnatal d 20 (juvenile) and adulthood. At d 20, resting respiratory variables were not affected by the treatments. Juvenile NCT male rats showed a 22% higher minute ventilation response to hypercapnia than vehicle rats. However, oral gavage alone increased the frequency component of the response by 11%. In adult males, caffeine increased the resting respiratory frequency by 15%. In these animals, the tidal volume response to hypercapnia was increased by 15%, whereas the frequency response was decreased by 20%. In juvenile and adult females, no differences were observed between treatments. In juvenile rats of both sexes, gavage increased the apnea index by at least 200%. These results show that NCT and gavage influence respiratory control during early life and that these effects persist until adulthood. The underlying mechanisms are unclear, but may be related to persistent changes in adenosinergic neurotransmission because neonatal caffeine administration increases A1 adenosine receptor density in adult rats.
 ...
PMID:Long-term consequences of neonatal caffeine on ventilation, occurrence of apneas, and hypercapnic chemoreflex in male and female rats. 1654 22

High tidal volume ventilation is detrimental to alveolar fluid clearance (AFC), but effects of ventilation pressure (P) on AFC are unknown. In anesthetized BALB/c mice ventilated at constant tidal volume (8 ml/kg), mean AFC rate was 12.8% at 6 cmH(2)O P, but increased to 37.3% at 18 cmH(2)O P. AFC rate declined at 22 cmH(2)O P, which also induced lung damage. Increased AFC at 18 cmH(2)O P did not result from elevated plasma catecholamines, hypercapnia, or hypocapnia, but was due to augmented Na(+) and Cl(-) absorption. PKA agonists and beta-agonists stimulated AFC at 10 cmH(2)O P by upregulating amiloride-sensitive Na(+) transport. However, at 18 cmH(2)O P, PKA agonists and beta-agonists reduced AFC. At 15 cmH(2)O P, the AFC rate was intermediate (mean 26.6%), and forskolin and beta-agonists had no effect. Comparable P dependency of AFC and beta-agonist responsiveness was found in C57BL/6 mice. The effect on AFC of increasing P to 18 cmH(2)O was blocked by adenosine deaminase or an A(2b)-adenosine receptor antagonist, and could be mimicked by adenosine in mice ventilated at 10 cmH(2)O P. Modulation of adenosine signaling also resulted in altered responsiveness to beta-agonists. These findings indicate that, in the normal mouse lung, basal AFC rates and responses to beta-agonists are impacted by ventilation pressure in an adenosine-dependent manner.
 ...
PMID:Effect of ventilation pressure on alveolar fluid clearance and beta-agonist responses in mice. 1968 2

Caffeine is commonly used clinically to treat apnoeas and unstable breathing associated with premature birth. Caffeine antagonizes adenosine receptors and acts as an efficient respiratory stimulant in neonates. Owing to its persistent effects on adenosine receptor expression in the brain, neonatal caffeine administration also has significant effects on maturation of the respiratory control system. However, since adenosine receptors are critically involved in sleep regulation, and sleep also modulates breathing, we tested the hypothesis that neonatal caffeine treatment disrupts regulation of sleep and breathing in the adult rat. Neonatal caffeine treatment (15 mg kg(-1) day(-1)) was administered from postnatal days 3-12. At adulthood (8-10 weeks old), sleep and breathing were measured with a telemetry system and whole-body plethysmography respectively. In adult rats treated with caffeine during the neonatal period, sleep time was reduced, sleep onset latency was increased, and non-rapid eye movement (non-REM) sleep was fragmented compared to controls. Ventilation at rest was higher in caffeine-treated adult rats compared to controls across sleep/wake states. Hypercapnic ventilatory responses were significantly reduced in caffeine-treated rats compared to control rats across sleep/wake states. Additional experiments in adult anaesthetized rats showed that at similar levels of arterial blood gases, phrenic nerve activity was enhanced in caffeine-treated rats. This study demonstrates that administration of caffeine in the neonatal period alters respiratory control system activity in awake and sleeping rats, as well as in the anaesthetized rats, and also has persistent disrupting effects on sleep that are apparent in adult rats.
 ...
PMID:Caffeine in the neonatal period induces long-lasting changes in sleep and breathing in adult rats. 1991 11

We studied the role of the role of mitoK+ATp channels and Al-adenosine receptor in the mechanism of increasing the resistance to acute hypoxia after hypoxic, hypercapnic and hypercapnic-hypoxic preconditioning. It is shown that mitochondrial ATP-sensitive potassium channels and Al-adenosine receptors, an important mechanism of preconditioning have a high value to increase the resistance to acute hypoxia/ischemia in the combined effect of hypoxia and hypercapnia. However, with regard to the adenosine receptor, this mechanism is realized without the participation hypercapnic component, which apparently starts neuroprotection without activation of the adenosine Al receptors.
 ...
PMID:[The role of adenosine Al receptors and mitochondrial K+ATP channels in the mechanism of increasing the resistance to acute hypoxia in the combined effects of hypoxia and hypercapnia]. 2598 Feb 26


1 2 Next >>