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

The membrane potential hypothesis that the responses to hypercapnia of carotid chemosensory activity is mediated by voltage-gated Ca2+ channels was investigated by measuring directly the chemosensory output from rat and cat carotid bodies, perfused and superfused in vitro. We found that the inorganic and organic blockers of voltage-gated Ca2+ channels suppressed the hypercapnic responses, thereby supporting the membrane potential hypothesis.
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PMID:Acid-sensing by carotid body is inhibited by blockers of voltage-sensitive Ca2+ channels. 937 13

We compare and contrast the putative mechanisms underlying CO2 chemoreceptor function in air breathing vertebrates and terrestrial pulmonate snails. We discuss the role of intracellular pH (pHi) in central respiratory responses to CO2 and describe a variety of patterns of pHi regulation in chemosensory areas. One pattern, in which pHi retains a fixed relationship to the CO2 stimulus over time, seems well suited to chemoreceptor cells. Alphastat regulation of ventilation is apparent in both air breathing vertebrates and terrestrial pulmonate snails. Diethyl pyrocarbonate inhibits respiratory responses to hypercapnia in both groups of animals. The neuronal basis of chemosensitivity is similar, in that putative chemoreceptor cells depolarize during hypercapnic stimulation, but the ionic basis of excitability appears to be a potassium conductance in the vertebrates studied to date and a calcium conductance in the snails. Despite divergent evolutionary histories, chemosensory responses and mechanisms are remarkably similar in air breathing vertebrates and terrestrial pulmonate snails.
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PMID:Comparative aspects of central CO2 chemoreception. 940 10

Although previous results have shown unequivocally that pre-ischaemic hyperglycaemia aggravates brain damage due to transient ischaemia, several questions have remained unanswered. First, is the effect of hyperglycaemia due to a further fall in intra- and extracellular pH? Second, is aggravation of damage a step function of a continuous function of plasma glucose concentration or of pH? Third, which are the mechanisms responsible for aggravation of damage, notably for the transformation of selective neuronal damage to infarction, for oedema development, and for post-ischaemic seizures? Recent results have provided new information on all of these issues. Thus, normoglycaemic animals with superimposed hypercapnia showed a similar, albeit not identical, aggravation of ischaemic damage, suggesting that acidosis is one major mediator. Furthermore, experiments with graded increase in plasma glucose concentration revealed a threshold effect at values of 10-12 mM, while microelectrode measurements showed a narrow extracellular pH range (6.4-6.5) for post-ischaemic seizure development. These results suggest that aggravation of damage due to excessive acidosis is due to mechanisms with a steep pH dependence. Finally, results are now at hand suggesting that the effect of acidosis is not mediated by a further perturbation of cell calcium metabolism. The more likely mediators are free radicals. Thus, acidosis is known to enhance iron-catalysed production of reactive oxygen species, probably by releasing iron from its bindings to transferrin, ferritin and other proteins.
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PMID:Role of hyperglycaemia-related acidosis in ischaemic brain damage. 942 66

The cellular mechanism responsible for the reduction of tension in cerebral small arteries to acidosis is not known. In this study the role of smooth muscle intracellular Ca2+ concentration ([Ca2+]i) and membrane potential for the relaxation to acidosis was investigated in isolated rat cerebral small arteries. Isometric force was measured simultaneously with [Ca2+]i (fura 2) or with membrane potential (intracellular microelectrodes), and acidosis was induced by increasing PCO2 or reducing HCO3- of the bathing solution. Both hypercapnic and normocapnic acidosis were associated with a reduction of intracellular pH [measured with 2',7'-bis-(carboxyethyl)-5 (and -6)-carboxyfluorescein], caused relaxation, and reduced [Ca2+]i. However, whereas hypercapnic acidosis caused hyperpolarization, normocapnic acidosis was associated with depolarization. It is concluded that a reduction of [Ca2+]i is in part responsible for the direct effect of the acidosis on the vascular smooth muscle both during normo- and hypercapnia. The mechanism responsible for the reduction of [Ca2+]i differs between the hypercapnic and normocapnic acidosis, being partly explained by hyperpolarization during hypercapnic acidosis, whereas it is seen despite depolarization during normocapnic acidosis.
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PMID:Effect of acidosis on tension and [Ca2+]i in rat cerebral arteries: is there a role for membrane potential? 948 71

Respiratory muscle injury may result from excessive loading due to a decrease in respiratory muscle strength, an increase in the work of breathing, or an increase in the rate of ventilation. Other conditions such as hypoxemia, hypercapnia, aging, decreased nutrition, and immobilization may potentiate respiratory muscle injury. Respiratory muscle injury has been shown in animal models using direct muscle or phrenic nerve stimulation, acute inspiratory resistive loading, tracheal banding, corticosteroids, phrenic nerve section, and the mdx mouse. Although numerous examples of diaphragm injury have been shown in animal models, evidence in humans is sparse. Potential mechanisms which may contribute to respiratory muscle injury include high levels of intracellular calcium-activated degradative enzymes, non-uniformity of stresses and strains, plasma membrane disruptions, and activation of the inflammatory process.
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PMID:Respiratory muscle injury in animal models and humans. 954 50

The conclusion that cyclic 3'-5 guanosine monophosphate (cGMP) functions in a 'permissive' manner in promoting cerebrovasodilation during hypercapnia was based on findings showing that the nitric oxide synthase (NOS) inhibitor-induced repression of the CO2 response could be reversed upon addition of exogenous cGMP. We hypothesized that the action of cGMP revealed in those studies does not define its normal role in hypercapnic cerebral vasodilation, but rather is a unique function of the artificial situation of NOS inhibition coupled with cGMP repletion. Thus, although CO2 reactivity may be the same in normal versus cGMP-repleted animals, the factors contributing to that response may differ. To test that possibility, the effects of calcium-dependent (KCa) or ATP-sensitive (KATP) potassium channel blockers on pial arteriolar CO2 reactivity, in vivo, were evaluated in the presence and absence of NOS inhibition plus administration of a cGMP analogue. Pial arteriolar diameter changes in hypercapnia were measured in three principal groups of anesthetized rats: (I) KCa channel-inhibited (via iberiotoxin); (II) KATP channel-inhibited (via glibenclamide); and (III) controls. Group I and II rats were further divided into: (a) those treated with the neuronal NOS (nNOS) inhibitor, 7-nitroindazole (7-NI), followed by successive suffusions of the cGMP analogue, 8-bromo-cGMP (8Br-cGMP) and 8Br-cGMP+K-channel blocker; and (b) rats where 7-NI and 8Br-cGMP applications were omitted. Group III rats were divided into time and 8Br-cGMP controls. Hypercapnia (PCO2 congruent with60 mmHg, 3 min)-induced dilations were reduced by 70-80% following 7-NI and restored by 8Br-cGMP. That restoration was reversed by both K-channel blockers. In the absence of 7-NI and exogenous cGMP, CO2 reactivity was unaffected by K-channel inhibition. These findings confirmed that nNOS-derived NO is critically important to the hypercapnic reactivity of cerebral arterioles, and that cGMP repletion, following NOS inhibition, could restore CO2 reactivity. The observation that KCa and KATP channel blockade did not alter CO2 reactivity under baseline conditions, but attenuated CO2 reactivity only in the presence nNOS inhibition (and cGMP repletion), suggests that multiple, redundant, and interactive mechanisms participate in CO2-induced vasodilation. These results also imply that current strategies for revealing permissive actions of cGMP (or NO) may need to be re-evaluated.
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PMID:Calcium-dependent and ATP-sensitive potassium channels and the 'permissive' function of cyclic GMP in hypercapnia-induced pial arteriolar relaxation. 963 Jun 23

The hypothesis that dopamine (DA) overflow corresponds to carotid sinus nerve (CSN) discharge during hypercapnia and is dependent on [Ca2+]0 was tested. We simultaneously measured the time course of DA overflow and CSN discharge of the cat carotid body, perfused/superfused in vitro at 37 degrees C at decreasing [Ca2+]0, during transition from normocapnia (PCO2 approximately 30-35 Torr) to hypercapnia (PCO2 approximately 60-65 Torr). In the presence of normal [Ca2+]0, hypercapnia instantaneously increased nerve discharge to peak levels followed by a decrease to steady states which were above the basal rate of activity. CSN discharge rate did not differ at decreasing [Ca2+]0 between 2.2 and 1.0 mM, and it began to decline at 0.1 mM [Ca2+]0, culminating to zero level in most cases, at zero [Ca2+]0. DA overflow increased slightly during hypercapnic peak CSN activity. Thereafter it declined to steady state levels below those of normocapnic conditions. Decreases in steady state DA levels were significantly less at 0 mM [Ca2+]0 compared to the higher calcium concentrations (0.1, 1.0 and 2.2 mM). Overall, steady state CSN activity and DA overflow were inversely related. Thus, DA release cannot have excitatory implications for carotid chemoreceptors during hypercapnia in the cat.
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PMID:Inhibition of dopamine release with simultaneous chemosensory excitation by hypercapnia with and without [Ca2+]0 in the cat carotid body. 969 75

The present study addresses the hypothesis that CO produced from endogenous heme oxygenase (HO) can dilate newborn cerebral arterioles. HO-2 protein was highly expressed in large and small blood vessels, as well as parenchyma, of newborn pig cerebrum. Topically applied CO dose-dependently dilated piglet pial arterioles in vivo over the range 10(-11)-10(-9) M (maximal response). CO-induced cerebrovascular dilation was abolished by treatment with the Ca2+-activated K+ channel inhibitors tetraethylammonium chloride and iberiotoxin. The HO substrate heme-L-lysinate also produced tetraethylammonium-inhibitable, dose-dependent dilation from 5 x 10(-8) to 5 x 10(-7) M (maximal). The HO inhibitor chromium mesoporphyrin blocked dilation of pial arterioles in response to heme-L-lysinate. In addition to inhibiting dilation to heme-L-lysinate, chromium mesoporphyrin also blocked pial arteriolar dilations in response to hypoxia but did not alter responses to hypercapnia or isoproterenol. We conclude that CO dilates pial arterioles via activation of Ca2+-activated K+ channels and that endogenous HO-2 potentially can produce sufficient CO to produce the dilation.
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PMID:Carbon monoxide and cerebral microvascular tone in newborn pigs. 1033 Feb 49

Systemic hyperglycemia and hypercapnia severely aggravate ischemic brain damage when instituted prior to cerebral ischemia. An aberrant cell signaling following ischemia has been proposed to be involved in ischemic cell death, affecting protein kinase C (PKC) and the calcium calmodulin kinase II (CaMKII). Using a cardiac arrest model of global brain ischemia of 10 min duration, we investigated the effect of hyperglycemia (20 mM) and hypercapnia (pCO(2) 300 mmHg) on the subcellular redistribution of PKC (alpha, beta, gamma) and CaMKII to synaptic membranes and to the microsomes, as well as the effect on PKC activity. We confirmed the marked translocation of PKC and CaMKII to cell membranes induced by ischemia, concomitantly with a decrease in the PKC activity in both the membrane fraction and cytosol. Hyperglycemia and hypercapnia markedly enhanced the translocation of PKC-gamma to cell membranes while other PKC isoforms were less affected. There was no effect of acidosis on PKC activity, or on translocation of CaMKII to cell membranes. Our data strongly suggest that the enhanced translocation of PKC to cell membranes induced by hyperglycemia and hypercapnia may contribute to the detrimental effect of tissue acidosis on the outcome following ischemia.
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PMID:Acidosis enhances translocation of protein kinase C but not Ca(2+)/calmodulin-dependent protein kinase II to cell membranes during complete cerebral ischemia. 1059 93

Since glomus cell intracellular calcium ([Ca(2+)](i)) plays a key role in generating carotid sinus nerve (CSN) discharge, we hypothesized that glomus cell [Ca(2+)](i) would correspond to CSN discharge rates during P(O(2))-P(CO(2)) stimulus interaction in adult rat carotid body (CB). Accordingly, we measured steady state P(O(2))-P(CO(2)) interaction in CSN discharge rates during hypocapnia (P(CO(2))=8-10 Torr), normocapnia (P(CO(2))=33-35 Torr) and hypercapnia (P(CO(2))=68-70 Torr) in normoxia (P(O(2)) approximately 130 Torr) and hypoxia (P(O(2)) approximately 36 Torr). The results showed P(O(2))-P(CO(2)) stimulus interaction in CSN responses. [Ca(2+)](i) levels were measured in isolated type I cells (2-3 cells/field), using Ca(2+) sensitive fluoroprobe indo-1AM. The [Ca(2+)](i) responses increased with increasing P(CO(2)) in normoxia. In hypoxia, [Ca(2+)](i) did not increase during hypocapnia but increased during normocapnia, showing P(O(2))-P(CO(2)) interaction. However, CSN response during hypoxia was far greater than that for [Ca(2+)](i) response, particularly during hypocapnic hypoxia. Thus, the [Ca(2+)](i) interaction cannot account for the whole CSN interaction. The origin of this CSN P(O(2)-)P(CO(2)) interaction must have occurred in part beyond cellular [Ca(2+)](i) interaction. Interactions at both sites (glomus cell membrane and sinus nerve endings) are reminiscent of reversible O(2)-heme protein reaction with a Bohr effect.
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PMID:P(O(2))-P(CO(2)) stimulus interaction in [Ca(2+)](i) and CSN activity in the adult rat carotid body. 1093 97


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