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

Pulmonary edema is cleared via active Na(+) transport by alveolar epithelial Na(+)/K(+)-ATPases and Na(+) channels. Rats exposed to acute hyperoxia have a high mortality rate, decreased Na(+)/K(+)-ATPase function, and decreased alveolar fluid clearance (AFC). We hypothesized that Na(+)/K(+)-ATPase subunit gene overexpression could improve AFC in rats exposed to hyperoxia. We delivered 4 x 10(9) PFU of recombinant adenoviruses containing rat alpha(1) and beta(1) Na(+)/K(+)-ATPase subunit cDNAs (adalpha(1) and adbeta(1), respectively) to rat lungs 7 days prior to exposure to 100% O(2) for 64 hr. As compared with controls and ad alpha(1), AFC in the adbeta(1) rats was increased by >300%. Permeability for large solutes was less in the ad beta(1) than in the other hyperoxia groups. Glutathione oxidation, but not superoxide dismutase activity, was increased only in the adbeta(1) group. Survival through 14 days of hyperoxia was 100% in the adbeta(1) group but was not different from hyperoxic controls in animals given adalpha(1). Our data show that overexpression of a beta(1) Na(+)/K(+)-ATPase subunit augments AFC and improves survival in this model of acute lung injury via antioxidant-independent mechanisms. Conceivably, restoration of AFC via gene transfer of Na(+)/K(+)-ATPase subunit genes may prove useful for the treatment of acute lung injury and pulmonary edema.
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PMID:Adenovirus-mediated transfer of an Na+/K+-ATPase beta1 subunit gene improves alveolar fluid clearance and survival in hyperoxic rats. 1108 80

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.
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PMID:The dysfunction of ATPases due to impaired mitochondrial respiration in phosgene-induced pulmonary edema. 1816 70

Hypoxia impairs alveolar fluid clearance by inhibition of Na(+) reabsorption, and also impairs beta(2) adrenergic signaling in alveolar epithelium. Since both are major rescue mechanisms preventing pulmonary edema, we studied whether acute and prolonged treatment with terbutaline would prevent hypoxic inhibition of ion transport. Short circuit currents (ISC) were measured on normoxic and hypoxic (1.5% O(2); 24h) primary rat alveolar type II (ATII) cells in absence and presence of terbutaline (1 to 100 microM, 24h). Control and pre-treated cells were stimulated acutely with terbutaline. Transepithelial transport was measured as short circuit current (ISC) in Ussing chambers. Terbutaline induced a rapid decrease ISC (-20%) followed by a slow raise. The transient change in ISC was not inhibited by amiloride but was prevented after Cl(-) depletion indicating a Cl(-) current. The slow increase after this transient was amiloride-sensitive indicating a Na(+) current. Total ISC, its amiloride-sensitive component, and the transient decrease upon terbutaline stimulation were decreased by hypoxia. 24h treatment with terbutaline stimulated these currents in normoxia and hypoxia, although stimulation was less in the latter. 24h treatment with terbutaline increased the capacity of Na(+)/K(+)-ATPase and ENaC as measured after permeabilization with amphotericin. These changes were not paralleled by altered mRNA expression. Acutely applied terbutaline induced a 4-fold increase in cAMP formation in normoxia; terbutaline-induced cAMP-formation was impaired by hypoxia (-20%). Pre-treatment with terbutaline for 24h decreased terbutaline-induced cAMP formation by 85%. Despite this desensitization, addition of terbutaline to terbutaline pre-treated cells caused a larger increase in Cl(-) and Na(+) transport both in normoxia and hypoxia than in non pre-treated cells. These results indicate that beta(2) adrenergic stimulation increased Na(+)- and Cl(-) transport in ATII cells even in hypoxia thus restoring normal reabsorption.
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PMID:Beta2-adrenergic stimulation blunts inhibition of epithelial ion transport by hypoxia of rat alveolar epithelial cells. 2005 51

Dexamethasone has been found to reduce the incidence of high-altitude pulmonary oedema. Mechanisms explaining this effect still remain unclear. We assessed the effect of dexamethasone using established cell lines, including rat alveolar epithelial cells (AEC), pulmonary artery endothelial cells (RPAEC) and alveolar macrophages (MAC), in an environment of low oxygen, simulating a condition of alveolar hypoxia as found at high altitude. Inflammatory mediators and ion transporter expression were quantified. Based on earlier results, we hypothesized that hypoxic conditions trigger inflammation. AEC, RPAEC and MAC, pre-incubated for 1 h with or without dexamethasone (10(-7) mol/l), were subsequently exposed to mild hypoxia (5% O(2), or normoxia as control) for 24 h. mRNA and protein levels of cytokine-induced neutrophil chemoattractant-1, monocyte chemoattractant protein-1 and interleukin-6 were analysed. mRNA expression and functional activity of the apical epithelial sodium channel and basolateral Na(+)/K(+)-ATPase were determined using radioactive marker ions. In all three types of pulmonary cells hypoxic conditions led to an attenuated secretion of inflammatory mediators, which was even more pronounced in dexamethasone pretreated samples. Function of Na(+)/K(+)-ATPase was not significantly influenced by hypoxia or dexamethasone, while activity of epithelial sodium channels was decreased under hypoxic conditions. When pre-incubated with dexamethasone, however, transporter activity was partially maintained. These findings illustrate that long-term hypoxia does not trigger an inflammatory response. The ion transport across apical epithelial sodium channels under hypoxic conditions is ameliorated in cells treated with dexamethasone.
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PMID:Effect of hypoxia and dexamethasone on inflammation and ion transporter function in pulmonary cells. 2277 86