Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085383 (hypocapnia)
 1,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The hydrogen ion is an important factor in the alteration of vascular tone in pulmonary circulation. Endothelial cells modulate vascular tone by producing vasoactive substances such as prostacyclin (PGI2) through a process depending on intracellular Ca2+ concentration ([Ca2+]i). We studied the influence of CO2-related pH changes on [Ca2+]i and PGI2 production in human pulmonary artery endothelial cells (HPAECs). Hypercapnic acidosis appreciably increased [Ca2+]i from 112 +/- 24 to 157 +/- 38 nmol/l. Intracellular acidification at a normal extracellular pH increased [Ca2+]i comparable to that observed during hypercapnic acidosis. The hypercapnia-induced increase in [Ca2+]i was unchanged by the removal of Ca2+ from the extracellular medium or by the depletion of thapsigargin-sensitive intracellular Ca2+ stores. Hypercapnic acidosis may thus release Ca2+ from pH-sensitive but thapsigargin-insensitive intracellular Ca2+ stores. Hypocapnic alkalosis caused a fivefold increase in [Ca2+]i compared with hypercapnic acidosis. Intracellular alkalinization at a normal extracellular pH did not affect [Ca2+]i. The hypocapnia-evoked increase in [Ca2+]i was decreased from 242 +/- 56 to 50 +/- 32 nmol/l by the removal of extracellular Ca2+. The main mechanism affecting the hypocapnia-dependent [Ca2+]i increase was thought to be the augmented influx of extracellular Ca2+ mediated by extracellular alkalosis. Hypercapnic acidosis caused little change in PGI2 production, but hypocapnic alkalosis increased it markedly. In conclusion, both hypercapnic acidosis and hypocapnic alkalosis increase [Ca2+]i in HPAECs, but the mechanisms and pathophysiological significance of these increases may differ qualitatively.
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PMID:Effects of hypercapnia and hypocapnia on [Ca2+]i mobilization in human pulmonary artery endothelial cells. 1135 71

The hypothesis that intracellular calcium ([Ca(2+)](i)) release in glomus cells via ryanodine receptor (RyR) activation by caffeine may be independent of natural stimuli and chemosensory discharge was tested in the rat carotid body (CB). CB type I cells were isolated, plated and preloaded with calcium-sensitive fluorescent probe, Indo-1AM. With the increase of caffeine dose (0-50 mM) cytosolic calcium ([Ca(2+)](c)) increased from 85+/-15 nM to 1933+/-190 nM (n=6) at normoxia (PO(2)=125-130 Torr, PCO(2)=25-30 Torr, pH 7.30-7.35). Hypoxia (PO(2)=10-15 Torr) increased and hypocapnia (PCO(2)=7-9 Torr) decreased the cytoplasmic calcium [Ca(2+)](c) levels, independent of caffeine. Caffeine-related [Ca(2+)](c) increase was the same in the presence and the absence of extracellular calcium ([Ca(2+)](o)), indicating the source of Ca(2+) ions is the cellular store. Permeabilization of the cell membrane with saponin (25 microg/ml) retained the caffeine response. Additional treatment of the cells with 50 microM ryanodine (an inhibitor of the caffeine-activated RyR site) abolished caffeine-stimulated response. In vitro CB chemosensory (carotid sinus nerve, CSN) responses to hypoxia (PO(2)=35-40 Torr) were not altered by caffeine. These results suggest that [Ca(2+)](i) stores in CB cells, mobilized by RyR activation, do not participate in the CSN responses to natural stimuli.
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PMID:Ryanodine receptor-mediated [Ca(2+)](i) release in glomus cells is independent of natural stimuli and does not participate in the chemosensory responses of the rat carotid body. 1159 88

23% of all septic patients develop septic encephalopathy which is associated with an increased mortality rate. Symptoms such as agitation, confusion and disorientation ranging from stupor to coma often develop in early sepsis. Severe hypotension is significantly associated with the development of septic encephalopathy. Several other factors which may play a role are also discussed: effects of inflammatory mediators on the brain, inadequate cerebral perfusion pressure, blood-brain barrier derangements, disturbances of the cerebral microcirculation, cerebral ischemia e.g. due to hypocapnia,metabolic changes, altered amino acid levels, transmitter imbalances, liver insufficiency, multiple organ failure and infections of the CNS, respectively. Compared to patients with an isolated infection,patients in septic shock have increased levels of aromatic amino acids such as phenylalanine and tryptophan in the plasma and brain as well as decreased levels of branched chain amino acids. Patients who died had higher levels of aromatic amino acids than the survivors. The correlation between aromatic amino acids and the APACHE II score was significant. The tryptophan metabolite quinolinic acid which can be synthesized in activated macrophages could act as an excitatory transmitter on the N-methyl-D-aspartate (NMDA) -receptor. Observations from experimental models indicate that activated NMDA receptors activate the neuronal isoform of the NO-synthase and other calcium dependent enzymes. This releases free radicals which may damage the DNA and activate the nuclear enzyme Poly-ADP-ribose-synthetase (PARS), resulting in energy depletion and cell death. Sepsis is the main cause of metabolic encephalopathies in critically ill patients. The differential diagnoses include hepatic, renal,hypoxic-ischemic or cardiovascular encephalopathies as well as encephalopathies,metabolic disorders and organ dysfunctions of other origin. Therapeutic interventions are numerous,however, so far only investigated in few controlled studies. The primary therapeutic goal is to maintain an adequate perfusion pressure and to prevent hypoxia and hypocapnia. Although the infusion of branched chain amino acids is controversial, experimental investigations demonstrated improvements improvements in an animal model with septic encephalopathy. Further investigations with respect to glutamate receptor antagonists, new radical scavengers, NO- and PARS-inhibitors may show whether these substances are suitable for the prophylaxis or early therapy of septic encephalopathy.
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PMID:[Septic encephalopathy. Diagnosis und therapy]. 1275 14

During voluntary hyperventilation in unanesthetized humans, hypocapnia causes coronary vasoconstriction and decreased oxygen (O(2)) supply and availability to the heart. This can induce local epicardial coronary artery spasm in susceptible patients. Its diagnostic potential for detection of early heart disease is unclear. This is because such hypocapnia produces an inconsistent and irreproducible effect on electrocardiogram (ECG) in healthy subjects. To resolve this inconsistency, we have applied two new experimental techniques in normal, healthy subjects to measure the effects of hypocapnia on their ECG: mechanical hyperventilation and averaging of multiple ECG cycles. In 15 normal subjects, we show that hypocapnia (20 +/- 1 mmHg) significantly reduced mean T wave amplitude by 0.1 +/- 0.0 mV. Hypocapnia also increased mean heart rate by 4 beats/min without significantly altering blood pressure, ionized calcium or potassium levels, or the R wave or other features of the ECG. We therefore provide the first unequivocal demonstration that hypocapnia does consistently reduce T wave amplitude in normal, healthy subjects.
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PMID:Hypocapnia reduces the T wave of the electrocardiogram in normal human subjects. 1576 Nov 87

Nimodipine is a calcium entry blocker that shows promise in the therapy for cerebral ischemia. This study was undertaken to examine the interaction of nimodipine with the use of hypocapnia to control cerebral blood volume by reduction in cerebral blood flow (CBF), as might be applicable to patients undergoing anesthesia for neurosurgical procedures. Male adult Sprague-Dawley rats were anesthetized with pentobarbital 50 mg/kg i.p. and were mechanically ventilated at either normocapnia (Paco2 35-40 mm Hg) or hypocapnia (Paco2 23-25 mm Hg). Animals were randomized into four experimental groups in a 2 x 2 factorial design, employing Paco2 level and drug group as between-group factors: vehicle plus normocapnia (group 1, n = 6), nimodipine plus normocapnia (group 2, n = 7), vehicle plus hypocapnia (group 3, n = 6), and nimodipine plus hypocapnia (group 4, n = 6). Nimodipine (1 mug/kg/min) or vehicle was administered i.v. for a period of 45 min. CBF was then measured using [C]iodoantipyrine autoradiography. Hypocapnia decreased global CBF (p <0.0001) and nimodipine increased CBF (p <0.05). Although nimodipine increased global CBF (p <0.05) during normocapnia (89 +/- 8 versus 61 +/- 4 ml/100 g/min), during hypocapnia there was no significant difference between nimodipine and vehicle (45 +/- 3 versus 40 +/- 2 ml/100 g/min). Hypocapnia decreased local CBF in all structures examined, whereas nimodipine increased local CBF in some, but not all structures. In this model, prior institution of hypocapnia prevented nimodipine-induced global CBF increases.
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PMID:Nimodipine does not increase cerebral blood flow during hypocapnia in the rat. 1581 65

The role of carbon dioxide (CO2) is underestimated in the pathomechanism of neuropsychiatric disorders, though it is an important link between psyche and corpus. The actual spiritual status also influences respiration (we start breathing rarely, frequently, irregularly, etc.) causing pH alteration in the organism; on the other hand the actual cytosolic pH of neurons is one of the main modifiers of Ca2+-conductance, hence breathing directly, quickly, and effectively influences the second messenger system through Ca2+-currents. (Decreasing pCO2 turns pH into alkalic direction, augments psychic arousal, while increasing pCO2 turns pH acidic, diminishes arousal.) One of the most important homeostatic function is to maintain or restore the permanence of H+-concentration, hence the alteration of CO2 level starts cascades of contraregulation. However it can be proved that there is no perfect compensation, therefore compensational mechanisms may generate psychosomatic disorders causing secondary alterations in the "milieu interieur". Authors discuss the special physico-chemical features of CO2, the laws of interweaving alterations of pCO2 and catecholamine levels (their feedback mechanism), the role of acute and chronic hypocapnia in several hyperarousal disorders (delirium, panic disorder, hyperventilation syndrome, generalized anxiety disorder, bipolar disorder), the role of "locus minoris resistentiae" in the pathomechanism of psychosomatic disorders. It is supposed that the diseases of civilization are caused not by the stress itself but the lack of human instinctive reaction to it, and this would cause long-lasting CO2 alteration. Increased brain-pCO2, acidic cytosol pH and/or increased basal cytosolic Ca2+ level diminish inward Ca2+-current into cytosol, decrease arousal--they may cause dysthymia or depression. This state usually co-exists with ATP-deficiency and decreased cytosolic Mg2+ content. This energetical- and ion-constellation is also typical of ageing-associated and chronic organic disorders. It is the most important link between depression and organic disorders (e.g. coronary heart disease). The above-mentioned model is supported by the fact that H+ and/or Ca2+ metabolism is affected by several drugs (catecholemines, serotonin, lithium, triaecetyluridine, thyroxine) and sleep deprivation, they act for the logically right direction.
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PMID:The role of carbon dioxide (and intracellular pH) in the pathomechanism of several mental disorders. Are the diseases of civilization caused by learnt behaviour, not the stress itself? 2012 95

The effects of two transportation periods on physio- metabolic hemodynamic changes and gaseous exchange in commercial swine during transportation to the slaughterhouse was studied in 684 pigs, 357 barrows and 327 gilts, transported in 2 groups for 8 and 16 h. Transportation caused an increase of oxygen consumption and body temperature, a decrease in pH, lactic acid accumulation. Both transportation periods caused higher than normal plasma glucose levels, lactic acidosis and evidence of dehydration. The linear regression analysis for pigs transported for 8h indicates that the PO(2,) lactate and Ca(++) variables correlated negatively with the PCO(2.) Whilst the animals that were transported for 16 h had negative correlations between glucose, and calcium, hematocrit, lactate and potassium levels. It was concluded that regardless of transport time acidosis, hypocapnia, hypoxaemia, hypernatraemia, hypercalcaemia, hyperglycemia, lactacidemia and increased hematocrit levels occurred.
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PMID:Changes in blood constituents of swine transported for 8 or 16 h to an Abattoir. 2073 49

Hypocapnia and hypercapnia constrict and relax airway smooth muscle, respectively, through pH- and calcium (Ca(2+))-mediated mechanisms. In this study we explore a potential role for the airway epithelium in these responses to carbon dioxide (CO(2)). Contractile and relaxant responses of isolated rat bronchial rings were measured under hypocapnic, eucapnic, and hypercapnic conditions. Substance P was added to methacholine precontracted bronchial rings with and without epithelium. The role of Ca(2+) was assessed using Ca(2+)-free solutions and a Ca(2+) channel blocker, nifedipine. The effects of pH were assessed in solutions with HEPES buffer. Hypocapnic challenge increased the organ bath's pH and increased bronchial smooth muscle resting tension. This effect was abolished with HEPES buffer and partially inhibited by nifedipine. Hypocapnic conditions suppressed substance P-induced epithelium-dependent relaxation, whereas hypercapnia augmented the response. The epithelial hypocapnic effect was pH dependent, whereas the hypercapnic effect was pH independent. CO(2) had no effect on the epithelial independent smooth muscle agonists methacholine and isoproterenol. In conclusion our data indicate that, in addition to the effects of pH and Ca(2+), CO(2) affects airway smooth muscle by a pH-independent, epithelium-mediated mechanism. These findings could potentially lead to new treatments for asthma involving CO(2)-sensing receptors in the airways.
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PMID:Carbon dioxide enhances substance P-induced epithelium-dependent bronchial smooth muscle relaxation in Sprague-Dawley rats. 2181 29

We present a woman with heterozygous carnitine palmitoyl transferase 2 (CPT-2) deficiency who in the last 6 months suffered from episodic dyspnea and choking. Symptoms could not be attributed to her muscular energy defect, since heterozygous CPT-2 deficiency is usually asymptomatic or causes only mild muscle fatigability. Myopathy is usually triggered by concurrent factors, either genetic (additional muscle enzymes defects) or acquired (metabolic stress). The patient was referred to our respiratory clinic for suspect bronchial asthma. Spirometry showed mild decrease in inspiratory flows. Methacholine challenge was negative. Dyspnea was triggered by hyperventilation-induced hypocapnia, which produced marked decrease in airflow rates, particularly in inspiratory flows, consistent with laryngospasm. Nutritional assessment of the patient showed low serum level of calcium and vitamin D, attributable to avoidance of milk and dairy products for lactose intolerance and to insufficient sunlight exposure. After calcium and vitamin D supplementation episodic laryngospasm disappeared and hypocapnic hyperventilation test induced very mild change in airflow rates. Calcium and vitamin D deficiency may favour laryngeal spasm mimicking asthma, particularly in subjects with underlying myopathy.
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PMID:Laryngeal spasm mimicking asthma and vitamin d deficiency. 2484 4


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