Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to examine the combined effect of nitric oxide (NO) and hyperoxia on lung edema and Na,K-ATPase expression. Newborn piglets were exposed to room air (FiO2 = 0.21), room air plus 50 ppm NO, hyperoxia (FiO2 >/= 0.96) or to hyperoxia plus 50 ppm NO for 4-5 days. Animals exposed to NO in room air experienced only a slight decrease in Na,K-ATPase alpha subunit protein level. Hyperoxia, in the absence of NO, induced both the mRNA and the protein level of Na,K-ATP-ase alpha subunit and significantly increased wet lung weight, extravascular lung water, and alveolar permeability. NO in hyperoxia decreased the hyperoxic-mediated induction of Na,K-ATPase alpha subunit mRNA and protein while wet lung weight, extravascular lung water, and alveolar permeability remained elevated. These results suggest that 50 ppm of inhaled NO may not improve hyperoxic-induced lung injury and may interfere with the expression of Na,K-ATPase which constitutes a part of the cellular defense mechanism against oxygen toxicity.
 ...
PMID:Influence of inhaled nitric oxide and hyperoxia on Na,K-ATPase expression and lung edema in newborn piglets. 992 7

Loss of alveolar barrier function is important in the development of pulmonary edema, but quantitation of its integrity has been difficult in the intact lung. We report a new non-radioactive method to assess paracellular and transcellular permeability of alveolar barrier in buffer-perfused rabbit lungs. Changes in alveolar barrier parameters were then correlated with different types of lung edema formation. The paracellular and transcellular barrier function was quantified by calculating the apparent epithelial permeability-surface area products (PS) for a fluorescent hydrophilic solute, FITC-dextran (FD-4), and a hydrophobic solute, rhodamine B, respectively. In control lungs, the apparent epithelial PS for FD-4 and rhodamine B were 0.7+/-0.05 x 10(-4) and 40.0+/-4.1 x 10(-4) ml/sec, respectively. The apparent epithelial PS of FD-4 could be increased 25-fold by inhibition of epithelial anion exchange with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) without affecting the PS of rhodamine B. The apparent epithelial PS of FD-4 could be increased 6- and 1.7-fold by disrupting microtubules with nocodazole and colchicine respectively, but microtubule agents decreased PS for rhodamine B. A pattern similar was produced when ATP production in the lung was inhibited by 2-deoxyglucose or when oxidative injury was induced by ischemia-reperfusion. Neither DIDS nor nocodazole altered endothelial permeability to albumin. DIDS, but not nocodazole, increased transcapillary liquid filtration and calculated interstitial compliance of the lung during hydrostatic challenge. We conclude that epithelial permeability in the intact lung can be assessed using fluorescent solutes, and that increased permeation of hydrophilic solutes may enhance lung edema formation.
 ...
PMID:Alveolar barrier function assessed by hydrophobic and hydrophilic fluorescent solutes in rabbit lung. 1238 40

Increased pulmonary capillary pressure and inhibition of alveolar Na+ transport putatively contribute to the formation of pulmonary edema in alveolar hypoxia such as at high altitude. Since both events might be linked to the inhibition of K+ channels, we studied whether in vivo application of minoxidil, a stimulator of ATP-gated K channels (K+ ATP channel activator) prevents both effects. In a double- blind, placebo-controlled crossover study on 17 volunteers with no known susceptibility to high altitude pulmonary edema, we tested whether a single dose of minoxidil (5 mg) prevents pulmonary hypertension and inhibition of nasal-epithelial Na+ transport in normobaric hypoxia (12% O2, 2 h). In hypoxia, arterial SO2 was decreased to about 80%, and systolic pulmonary artery pressure (PAP) measured by Doppler echocardiography increased significantly from approximately 25 mmHg (normoxia) to approximately 38 mmHg (hypoxia; range 22 to 61 mmHg). Minoxidil decreased PAP in hypoxia in those individuals who had the highest increase in PAP in hypoxia when taking placebo. Nasal potentials decreased by about 10% in hypoxia. Although minoxidil had no effect on nasal potentials in normoxia, it increased nasal potentials significantly above normoxic control values after 2-h hypoxia. These results show that the K+ ATP activator minoxidil prevents the decrease in nasal-epithelial potential by hypoxia and seems to blunt an exaggerated increase in PAP in acute hypoxia.
 ...
PMID:K+ channel activation with minoxidil stimulates nasal-epithelial ion transport and blunts exaggerated hypoxic pulmonary hypertension. 1654 67

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of acute respiratory failure associated with high morbidity and mortality. Although ALI/ARDS pathogenesis is only partly understood, pulmonary endothelium plays a major role by regulating lung fluid balance and pulmonary edema formation. Consequently, endothelium-targeted therapies may have beneficial effects in ALI/ARDS. Recently, attention has been given to the therapeutic potential of purinergic agonists and antagonists for the treatment of cardiovascular and pulmonary diseases. Extracellular purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are important signaling molecules that mediate diverse biological effects via cell-surface P2Y receptors. We previously described ATP-induced endothelial cell (EC) barrier enhancement via a complex cell signaling and hypothesized endothelial purinoreceptors activation to exert anti-inflammatory barrier-protective effects. To test this hypothesis, we used a murine model of ALI induced by intratracheal administration of endotoxin/lipopolysaccharide (LPS) and cultured pulmonary EC. The nonhydrolyzed ATP analog ATPgammaS (50-100 muM final blood concentration) attenuated inflammatory response with decreased accumulation of cells (48%, P < 0.01) and proteins (57%, P < 0.01) in bronchoalveolar lavage and reduced neutrophil infiltration and extravasation of Evans blue albumin dye into lung tissue. In cell culture model, ATPgammaS inhibited junctional permeability induced by LPS. These findings suggest that purinergic receptor stimulation exerts a protective role against ALI by preserving integrity of endothelial cell-cell junctions.
 ...
PMID:Protective effect of purinergic agonist ATPgammaS against acute lung injury. 1799 88

Phosgene is a toxic gas that is widely used in modern industry, and its inhalation can cause severe pulmonary edema. There is no effective clinical treatment because the mechanism of phosgene-induced pulmonary edema still remains unclear. Many studies have demonstrated that the Na(+)/K(+)-ATPase plays a critical role in clearing pulmonary edema and the inhibition of Na(+)/K(+)-ATPase protein expression has been found in many other pulmonary edema models. In the present study, after the mice were exposed to phosgene, there was serious pulmonary edema, indicating the dysfunction of the ATPases in mice. However, in vitro enzyme study showed that there were increases in the activities of the Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Further investigation showed that the ATP content and mitochondrial respiratory control ratio (RCR) in the lungs decreased significantly. The oxidative stress product, malondialdehyde (MDA), increased while the antioxidants (GSH, SOD, and TAC) decreased significantly. These results indicate that mitochondrial respiration is the target of phosgene. The dysfunction of ATPases due to impaired mitochondrial respiration may be a new mechanism of phosgene-induced pulmonary edema.
 ...
PMID:The dysfunction of ATPases due to impaired mitochondrial respiration in phosgene-induced pulmonary edema. 1816 70

Chronic obstructive lung diseases are characterized by the inability to prevent bacterial infection and a gradual loss of lung function caused by recurrent inflammatory responses. In the past decade, numerous studies have demonstrated the importance of nucleotide-mediated bacterial clearance. Their interaction with P2 receptors on airway epithelia provides a rapid 'on-and-off' signal stimulating mucus secretion, cilia beating activity and surface hydration. On the other hand, abnormally high ATP levels resulting from damaged epithelia and bacterial lysis may cause lung edema and exacerbate inflammatory responses. Airway ATP concentrations are regulated by ecto nucleoside triphosphate diphosphohydrolases (E-NTPDases) which are expressed on the mucosal surface and catalyze the sequential dephosphorylation of nucleoside triphosphates to nucleoside monophosphates (ATP --> ADP --> AMP). The common bacterial product, Pseudomonas aeruginosa lipopolysaccharide (LPS), induces an acute reduction in azide-sensitive E-NTPDase activities, followed by a sustained increase in activity as well as NTPDase 1 and NTPDase 3 expression. Accordingly, chronic lung diseases, including cystic fibrosis (CF) and primary ciliary dyskinesia, are characterized by higher rates of nucleotide elimination, azide-sensitive E-NTPDase activities and expression. This review integrates the biphasic regulation of airway E-NTPDases with the function of purine signaling in lung diseases. During acute insults, a transient reduction in E-NTPDase activities may be beneficial to stimulate ATP-mediated bacterial clearance. In chronic lung diseases, elevating E-NTPDase activities may represent an attempt to prevent P2 receptor desensitization and nucleotide-mediated lung damage.
 ...
PMID:E-NTPDases in human airways: Regulation and relevance for chronic lung diseases. 1840 79

Epithelia, in general, and the lung epithelium, in particular, are exposed to mechanical forces, but little is known about their impact on pulmonary ion transport. In our present study, we employed transepithelial ion transport measurements on Xenopus lung preparations using custom-built Ussing chambers. Tissues were exposed to mechanical stress by increasing the water column (5 cm) at one side of the tissues. Apical exposure to hydrostatic pressure significantly decreased the short circuit current (I (SC): 24 +/- 1%, n = 152), slightly decreased the transepithelial resistance (R (T): 7 +/- 2%, n = 152), but increased the apical membrane capacitance (C (M): 16 +/- 6%, n = 9). The pressure-induced effect was sensitive to Na+ (amiloride), Cl(-) (DIDS, NFA, NPPB) and K+ channel blockers (Ba2+), glibenclamide). Further on, it was accompanied by increased extracellular ATP levels. The results show that mechanical stress leads to an activation of Na+, Cl(-), and K+ conductances in a native pulmonary epithelium resulting in a net decrease of ion absorption. This could be of considerable interest, since an altered ion transport may contribute to pathophysiological conditions, e.g., the formation of pulmonary edema during artificial ventilation.
 ...
PMID:Impact of mechanical stress on ion transport in native lung epithelium (Xenopus laevis): short-term activation of Na+, Cl (-) and K+ channels. 1858 Nov 36

AMP-activated protein kinase (AMPK) is activated by increases in the intracellular AMP-to-ATP ratio and plays a central role in cellular responses to metabolic stress. Although activation of AMPK has been shown to have anti-inflammatory effects, there is little information concerning the role that AMPK may play in modulating neutrophil function and neutrophil-dependent inflammatory events, such as acute lung injury. To examine these issues, we determined the effects of pharmacological activators of AMPK, 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) and barberine, on Toll-like receptor 4 (TLR4)-induced neutrophil activation. AICAR and barberine dose-dependently activated AMPK in murine bone marrow neutrophils. Exposure of LPS-stimulated neutrophils to AICAR or barberine inhibited release of TNF-alpha and IL-6, as well as degradation of IkappaBalpha and nuclear translocation of NF-kappaB, compared with findings in neutrophil cultures that contained LPS without AICAR or barberine. Administration of AICAR to mice resulted in activation of AMPK in the lungs and was associated with decreased severity of LPS-induced lung injury, as determined by diminished neutrophil accumulation in the lungs, reduced interstitial pulmonary edema, and diminished levels of TNF-alpha and IL-6 in bronchoalveolar lavage fluid. These results suggest that AMPK activation reduces TLR4-induced neutrophil activation and diminishes the severity of neutrophil-driven proinflammatory processes, including acute lung injury.
 ...
PMID:Activation of AMPK attenuates neutrophil proinflammatory activity and decreases the severity of acute lung injury. 1858 54

Recent observations suggest the presence of 20S proteasomes (20S) in the lung epithelial lining fluid. However, the physiological relevance of 20S in the alveolar space and possible contribution to disease processes are unknown. Thus, we evaluated whether extracellular proteasomes could have a pathophysiological role in the injured lung using a rat model of lung contusion (LC). Bronchoalveolar lavage fluids (BALF) were obtained at various time points for up to 168 h after LC or sham procedure. Enzyme activities, ELISA and Western blots indicated enzymatically active 20S, the 19S subunit Rpt5 and ubiquitin in BALF. 20S and ubiquitin increased significantly after LC, peaked at 24 h and normalized within 168 h. Mg(2+)/ATP-dependent peptidase activities were detectable 6-24 h after LC. BALF after LC also contained ubiquitin-protein-ligase activity. Addition of Mg(2+)/ATP to BALF after LC led to significant proteolysis and could be prevented with epoxomicin and EDTA. These data suggest for the first time that the Mg(2+)/ATP-dependent 26S proteasome complex exists outside the cell, is released into the lung epithelial lining fluid after LC and contributes to the proteolysis of the bulk of protein in the alveolar space of the injured lung. We infer that proteasome complexes may have a pathophysiological role during lung edema clearance.
 ...
PMID:Detection and possible role of proteasomes in the bronchoalveolar space of the injured lung. 1863 7

Lung alveolar epithelial cells are normally very well oxygenated but may be exposed to hypoxia in many pathological conditions such as pulmonary edema, acute respiratory distress syndrome, chronic obstructive pulmonary diseases, or in some environmental conditions such ascent to high altitude. The ability of alveolar epithelial cells to cope with low oxygen tensions is crucial to maintain the structural and functional integrity of the alveolar epithelium. Alveolar epithelial cells appear to be remarkably tolerant to oxygen deprivation as they are able to maintain adequate cellular ATP content during prolonged hypoxic exposure when mitochondrial oxidative phosphorylation is limited. This property mostly relies on the ability of the cells to rapidly modify their gene expression program, stimulating the expression of genes involved in anaerobic energy supply and repressing expression of genes involved in some ATP-consuming cellular processes. This adaptive strategy of the cells is mostly, but not entirely, dependent on the expression of hypoxia-inducible factors (HIFs), known to be responsible for orchestrating a large number of hypoxia-sensitive genes. This review focuses on the role of HIF isoforms expressed in alveolar epithelial cells exposed to hypoxia and on the specific hypoxic gene regulation that takes place in alveolar epithelial cells either through HIF-dependent or -independent pathways.
 ...
PMID:Gene regulation in the adaptive process to hypoxia in lung epithelial cells. 1911 91


<< Previous 1 2 3 4 Next >>