losartan-potassium has been researched along with Hypercapnia* in 12 studies
1 trial(s) available for losartan-potassium and Hypercapnia
11 other study(ies) available for losartan-potassium and Hypercapnia
| Article | Year |
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Brain-derived erythropoietin protects from intermittent hypoxia-induced cardiorespiratory dysfunction and oxidative stress in mice.
Based on the fact that erythropoietin (Epo) administration in rodents protects against spatial learning and cognitive deficits induced by chronic intermittent hypoxia (CIH)-mediated oxidative damage, here we tested the hypothesis that Epo in the brain protects against cardiorespiratory disorders and oxidative stress induced by CIH in adult mice.. Adult control and transgenic mice overexpressing Epo in the brain only (Tg21) were exposed to CIH (21%-10% O2-10 cycles/hour-8 hours/day-7 days) or room air. After CIH exposure, we used the tail cuff method to measure arterial pressure, and whole-body plethysmography to assess the frequency of apneic episodes at rest, minute ventilation, and ventilatory responses to hypoxia and hypercapnia. Finally, the activity of pro-oxidant (XO-xanthine oxidase, and NADPH) and antioxidant (super oxide dismutase) enzymes was evaluated in the cerebral cortex and brainstem.. Exposure of control mice to CIH significantly increased the heart rate and arterial pressure, the number of apneic events, and the ventilatory response to hypoxia and hypercapnia. Furthermore, CIH increased the ratio of pro-oxidant to antioxidant enzymes in cortex and brainstem tissues. Both physiological and molecular changes induced by CIH were prevented in transgenic Tg21 mice.. We conclude that the neuroprotective effect of Epo prevents oxidative damage in the brain and cardiorespiratory disorders induced by CIH. Considering that Epo is used in clinics to treat chronic kidney disease and stroke, our data show convincing evidence suggesting that Epo may be a promising alternative drug to treat sleep-disorder breathing. Topics: Animals; Apnea; Arterial Pressure; Brain; Brain Stem; Cerebral Cortex; Erythropoietin; Heart Rate; Hypercapnia; Hypoxia; Male; Mice; Mice, Transgenic; NADP; Oxidative Stress; Plethysmography, Whole Body; Pulmonary Ventilation; Reactive Oxygen Species; Rest; Sleep Apnea Syndromes; Superoxide Dismutase; Xanthine Oxidase | 2018 |
Hematological changes in severe early onset growth-restricted fetuses with absent and reversed end-diastolic flow in the umbilical artery.
Erythropoietin seems to play an important role in the regulation of fetal hypoxemia. The present prospective study was designed to determine if changes in erythropoietin levels can be found in fetuses with severe early-onset growth restriction and hemodynamic compromise.. Erythropoietin, hemoglobin, hematocrit, platelet counts, normoblasts, lacate, arterial and venous blood gasses in the umbilical cord were determined in 42 fetuses with fetal growth restriction (IUGR) with absent (zero-flow) and 26 IUGR fetuses with retrograde end-diastolic flow (reverse-flow) in the umbilical artery. Color Doppler measurements were performed on the middle cerebral artery (PI) and ductus venosus [(S-a)/D and (S-a)/Vmean]. Erythropoietin concentrations were significantly lower in the zero-flow group (median: 128.0 mU/mL; range: 60.3-213 mU/mL) compared with the reverse-flow group (median: 202.5 mU/mL; range: 166-1182 mU/mL). Significant differences in median lactate concentrations were observed between the zero-flow group: 3.28 mmol/L (range; 2.3-4.7 mmol/L), and reverse-flow group: 5.6 mmol/L (range: 3.8-7.5 mmol/L). Fetuses with reverse-flow had significantly lower median platelet counts than fetuses with zero-flow (74 vs. 155/μL) and significantly lower normoblast counts (63 vs. 342/100 WBC).. Fetuses with severe IUGR due to chronic placental insufficiency and absent or reversed flow in the umbilical artery show increased erythropoietin levels. Topics: Blood Flow Velocity; Erythropoietin; Female; Fetal Growth Retardation; Humans; Hypercapnia; Hypoxia; Platelet Count; Pregnancy; Prospective Studies; Thrombocytopenia; Ultrasonography, Doppler, Color; Ultrasonography, Prenatal; Umbilical Arteries | 2017 |
Polycythemia and high levels of erythropoietin in blood and brain blunt the hypercapnic ventilatory response in adult mice.
Changes in arterial Po2, Pco2, and pH are the strongest stimuli sensed by peripheral and central chemoreceptors to adjust ventilation to the metabolic demand. Erythropoietin (Epo), the main regulator of red blood cell production, increases the hypoxic ventilatory response, an effect attributed to the presence of Epo receptors in both carotid bodies and key brainstem structures involved in integration of peripheral inputs and control of breathing. However, it is not known whether Epo also has an effect on the hypercapnic chemoreflex. In a first attempt to answer this question, we tested the hypothesis that Epo alters the ventilatory response to increased CO2 levels. Basal ventilation and hypercapnic ventilatory response (HCVR) were recorded from control mice and from two transgenic mouse lines constitutively expressing high levels of human Epo in brain only (Tg21) or in brain and plasma (Tg6), the latter leading to polycythemia. To tease apart the potential effects of polycythemia and levels of plasma Epo in the HCVR, control animals were injected with an Epo analog (Aranesp), and Tg6 mice were treated with the hemolytic agent phenylhydrazine after splenectomy. Ventilatory parameters measured by plethysmography in conscious mice were consistent with data from electrophysiological recordings in anesthetized animals and revealed a blunted HCVR in Tg6 mice. Polycythemia alone and increased levels of plasma Epo blunt the HCVR. In addition, Tg21 mice with an augmented level of cerebral Epo also had a decreased HCVR. We discuss the potential implications of these findings in several physiopathological conditions. Topics: Animals; Brain; Electrophysiological Phenomena; Erythropoietin; Gene Expression Regulation; Hypercapnia; Mice; Mice, Transgenic; Polycythemia; Respiratory Physiological Phenomena; Vagus Nerve | 2016 |
Hypercapnic ventilatory response is decreased in a mouse model of excessive erythrocytosis.
The impact of cerebral erythropoietin (Epo) in the regulation of the hypercapnic ventilatory response (HcVR) is controversial. While we reported that cerebral Epo does not affect the central chemosensitivity in C57Bl6 mice receiving an intracisternal injection of sEpoR (the endogenous antagonist of Epo), a recent study in transgenic mice with constitutive high levels of human Epo in brain and circulation (Tg6) and in brain only (Tg21), showed that Epo blunts the HcVR, maybe by interacting with central and peripheral chemoreceptors. High Epo serum levels in Tg6 mice lead to excessive erythrocytosis (hematocrit ~80-90%), the main symptom of chronic mountain sickness (CMS). These latter results support the hypothesis that reduced central chemosensitivity accounts for the hypoventilation observed in CMS patients. To solve this intriguing divergence, we reevaluate HcVR in Tg6 and Tg21 mouse lines, by assessing the metabolic rate [O consumption (V̇) and CO production (V̇)], a key factor modulating ventilation, the effect of which was not considered in the previous study. Our results showed that the decreased HcVR observed in Tg6 mice (~70% reduction; < 0.01) was due to a significant decrease in the metabolism (~40%; < 0.0001) rather than Epo's effect on CO chemosensitivity. Additional analysis in Tg21 mice did not reveal differences of HcVR or metabolism. We concluded that cerebral Epo does not modulate the central chemosensitivity system, and that a metabolic effect upon CO inhalation is responsible for decreased HcVR observed in Tg6 animals. As CMS patients also show decreased HcVR, our findings might help to better understand respiratory disorders at high altitude. Topics: Animals; Brain; Carbon Dioxide; Erythropoietin; Hypercapnia; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Polycythemia; Pulmonary Ventilation | 2016 |
Increased HIF-1α and HIF-2α accumulation, but decreased microvascular density, in chronic hyperoxia and hypercapnia in the mouse cerebral cortex.
The partial pressure of oxygen in the brain parenchyma is tightly controlled, and normal brain function is delicately sensitive to continuous and controlled oxygen delivery. The objective of this study was to determine brain angiogenic adaptive changes during chronic normobaric hyperoxia and hypercapnia in mice. Four-month-old C56BL/6 J mice were kept in a normobaric chamber at 50 % O2 and 2.5 % CO2 for up to 3 weeks. Normoxic littermates were kept adjacent to the chamber and maintained on the same schedule. Physiological variables were measured at time points throughout the 3 weeks or when the mice were sacrificed. Freshly collected or fixed brain specimens were analyzed by Western blot analysis and immunohistochemistry (IHC). We found significant accumulation of hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) and increased expression of erythropoietin (EPO), cyclooxygenase-2 (COX-2), and angiopoietin-2 (Ang-2) in hyperoxia and hypercapnia. Conversely, vascular endothelial growth factor (VEGF), and VEGF receptor-2 (KDR/Flk-1), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), and prolyl hydroxylase-2 (PHD-2) expressions were decreased in hyperoxia and hypercapnia. Capillary density was significantly diminished by the end of the 3rd week of hyperoxia and hypercapnia as compared to control. We conclude that HIF-independent mechanisms contribute to brain capillary density modulation that is continuously adjusted in accordance with tissue oxygen tension. Topics: Angiopoietin-2; Animals; Basic Helix-Loop-Helix Transcription Factors; Blood Gas Analysis; Cerebral Cortex; Cyclooxygenase 2; Erythropoietin; Hypercapnia; Hyperoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Male; Mice; Mice, Inbred C57BL; Microvessels; Neovascularization, Pathologic; Oxygen; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Transcription Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2 | 2013 |
Development of an in vitro model of myotube ischemia.
Critical limb ischemia causes severe damage to the skeletal muscle. This study develops a reproducible model of myotube ischemia by simulating, in vitro, the critical parameters that occur in skeletal muscle ischemia. Monolayers of C2C12 myoblasts were differentiated into mature myotubes and exposed to nutrition depletion, hypoxia and hypercapnia for variable time periods. A range of culture media and gas mixture combinations were used to obtain an optimum ischemic environment. Nuclear staining, cleaved caspase-3 and lactate dehydrogenase (LDH) release assay were used to assess apoptosis and myotube survival. HIF-1α concentration of cell lysates, pH of conditioned media as well as partial pressures of oxygen (PO₂) and carbon dioxide (PCO₂) in the media were used to confirm ischemic simulation. Culturing myotubes in depleted media, in a gas mixture containing 20% CO+80% N₂ for 6-12 h increased the PCO₂ and decreased the pH and PO₂ of culture media. This attempts to mimic the in vivo ischemic state of skeletal muscle. These conditions were used to study the potential tissue-protective effects of erythropoietin (EPO) in C2C12 myotubes exposed to ischemia. EPO (60 ng/ml) suppressed LDH release, decreased cleaved caspase-3 and reduced the number of apoptotic nuclei, suggesting significantly decreased ischemia-induced apoptosis in myotubes (P<0.01) and a potential role in tissue protection. Additional therapeutic agents designed for tissue protection can also be evaluated using this model. Topics: Animals; Apoptosis; Carbon Dioxide; Caspase 3; Cell Differentiation; Cell Line; Cell Nucleus; Chromatin; Erythropoietin; Hydrogen-Ion Concentration; Hypercapnia; Hypoxia; Ischemia; L-Lactate Dehydrogenase; Mice; Models, Biological; Muscle Fibers, Skeletal; Myoblasts, Skeletal; Oxygen; Receptors, Erythropoietin | 2011 |
[Circadian rhythm of serum erythropoietin in obstructive sleep apnea/hypoventilation syndrome].
Topics: Adult; Circadian Rhythm; Erythropoietin; Humans; Hypercapnia; Hyperoxia; Hypoventilation; Hypoxia; Male; Middle Aged; Sleep Apnea, Obstructive; Syndrome | 2004 |
[Hypoxia, acidosis and nephrology].
In a survey the correlations between hypoxia, acidosis and nephrology are presented. In chronic oxygen deficiency the individual aspects concern the uncertainties of erythropoietin and the carotid-sinusoidal natriuresis stimulated by chemoreceptors. The effects of acute ischaemic hypoxic reactions are described with regard to the acute renal failure. The regulatory renal function of acidification and its disturbance in chronic renal insufficiency as well as the renotubular acidosis are discussed. Finally the authors enter the influence on the renal function during positive pressure respiration (e.g. for the purpose of the normalisation of the pulmonary gas exchange in acute respiratory insufficiency) as well as on reactions of the haemodialysis (bicarbonate and acetate dialysis) to the blood gas and acid-base metabolism, taking into consideration the pulmonary function. Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Acidosis, Respiratory; Acute Kidney Injury; Erythropoietin; Glomerular Filtration Rate; Humans; Hypercapnia; Hypoxia; Kidney; Kidney Tubules; Natriuresis; Positive-Pressure Respiration; Renal Dialysis | 1987 |
Erythropoietin and intrarenal oxygenation in hypercapnic versus normocapnic hypoxemia.
Topics: Acidosis; Animals; Blood Gas Analysis; Electric Stimulation; Erythropoietin; Hemoglobins; Hypercapnia; Hypoxia; Iron; Kidney; Male; Oxygen Consumption; Protein Binding; Rabbits | 1984 |
Regulatory mechanism of erythropoietin production: effects of hypoxemia and hypercarbia.
The purpose of this study was twofold: (1) to define the relationship between erythropoietin (Ep) production and some of the coincident variables which control oxygen delivery in hypoxic and hypoxic-hypercarbic rats (2) to define the mechanism whereby hypercarbia suppresses Ep production in hypoxemic rats. Rats were exposed to O2 concentrations ranging from 5% to 9% O2 for either 3 or 16 h. Arterial whole blood pH, pCO2, pO2, O2 saturation, p50 and Ep levels were measured in each rat. There was a highly significant inverse correlation between both the arterial pO2 and O2 saturation and the Ep level. Ep levels were not increased above normal if the pO2 was greater than 50 mm Hg or the O2 saturation was greater than 80%. The addition of 5% CO2 to all inhaled gas mixtures was associated with a 10 mm Hg increment in the pO2 together with a marked reduction in plasma Ep levels. Of the measured variables only the pO2 and O2 saturation showed a consistent correlation with the Ep levels when rats exposed to hypoxia were compared with rats exposed to hypoxia + CO2. Topics: Alkalosis, Respiratory; Animals; Carbon Dioxide; Erythropoietin; Female; Hydrogen-Ion Concentration; Hypercapnia; Hypoxia; Iron; Oxygen; Rats | 1981 |
Inhibition of erythropoietin production in unanesthetized rabbits exposed to an acute hypoxic-hypercapnic environment.
Topics: Acute Disease; Anesthesia; Animals; Erythropoietin; Female; Hemoglobins; Hydrogen-Ion Concentration; Hypercapnia; Hypoxia; Lactates; Male; Mice; Oxygen; Oxygen Consumption; Phosphates; Rabbits; Time Factors | 1978 |