Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0034063 (pulmonary edema)
10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this work the influence of Bacillus anthracis toxin, introduced intraperitoneally in a dose of LD100, on the content of prostaglandins E and F2 alpha, 6-ketoprostaglandin F1 alpha, thromboxane, cAMP and cGMP in the lungs, heart, liver and spleen of BALB/c mice in the time course of experimental intoxication has been studied. The concentration and proportion of prostaglandins and cyclic nucleotides have been shown to undergo-sharp changes in all organs under study in the process of intoxication. The level and proportion of prostaglandins in the lungs ensures the development of vaso- and bronchodilatation processes even at early stages of the action of the toxin. B. anthracis toxin sharply increases the content of cGMP in the organs under study and cAMP in the liver. The activating effect on the adenylate cyclase system of tissue cells is not linked with the action of the edematous factor of the toxin. The role of cyclic nucleotides and prostaglandins in the development of pulmonary edema in intoxication with B. anthracis toxin is discussed.
...
PMID:[The prostaglandin and cyclic nucleotide levels in the organs of mice with experimental anthrax intoxication]. 165 40

A substantial body of evidence indicates that active transport of ions is important in modulating the resolution process of pulmonary edema. The biochemical regulation of this ion transport mechanism is still under investigation. In this study we evaluated the effect of an adenosine 3',5'-cyclic monophosphate (cAMP) analogue [dibutyryl cAMP (DBcAMP)] and a phosphodiesterase inhibitor (aminophylline) given alone or together on lung liquid and protein clearance. To study lung liquid and protein clearance, we measured the removal of 100 ml of autologous serum from the air spaces of anesthetized and ventilated adult sheep. Either serum alone or serum mixed with 10(-3) M DBcAMP, 10(-3) M or 10(-5) M aminophylline, or 10(-3) M aminophylline plus 10(-3) M DBcAMP was instilled. After 4 h, the residual lung water was 73.5 +/- 8.7 ml when serum alone was instilled and 56.8 +/- 13.6 ml when aminophylline and DBcAMP were given together. Neither aminophylline nor DBcAMP alone increased lung liquid clearance. However, the increase in clearance cannot be explained by an increase in protein clearance or changes in the pulmonary hemodynamics. These data suggest that the cAMP second messenger system can stimulate lung liquid clearance in vivo.
...
PMID:Effect of exogenous cAMP and aminophylline on alveolar and lung liquid clearance in anesthetized sheep. 165 7

A review of the factors that oppose pulmonary edema formation (alveolar flooding) when capillary pressure is elevated are presented for a normal capillary endothelial barrier and for damaged endothelium associated with ischemia/reperfusion in rabbit, rat, and dog lungs. Normally, tissue pressure, the plasma protein osmotic pressure gradient acting across the capillary wall and lymph flow (Edema Safety Factors) increase to prevent the build-up of fluid in the lung's interstitium when capillary pressure increases. No measureable alveolar edema fluid accumulates until capillary pressure exceeds 30 mmHg. When the capillary wall has been damaged, interstitial edema develops at lower capillary pressures because the plasma protein osmotic pressure will not change greatly to oppose capillary filtration, but lymph flow increases to very high levels to remove the increased filtrate and the result is that capillary pressures can increase to 20-25 mmHg before alveolar flooding results. In addition, the mechanisms responsible for producing pulmonary endothelial damage with ischemia/reperfusion are reviewed and the effects of O2 radical scavengers, neutrophil depletion or altering their adherence to the endothelium, and increasing cAMP on reversing the damage to the pulmonary endothelium is presented.
...
PMID:Pulmonary edema: ischemia reperfusion endothelial injury and its reversal by c-AMP. 166 19

The pathogenesis of adult respiratory distress syndrome (ARDS) is not clear, and its therapy is still a problem. Pentoxifylline, a methylxanthine derivative, can inhibit phosphodiesterase activity and thus increase the intracellular cAMP. There are also some hypotheses that pentoxifylline can attenuate pulmonary edema. In order to evaluate the protective effect of pentoxifylline in acute lung injury, we set up an isolated lung perfusion model in rats and induced experimental acute lung injury similar to ARDS by intravenously infused phorbol myristate acetate (PMA) 7.5 micrograms/300 g body weight. Four groups of experimental rats were studied: group 1, normal control group, neither PMA nor pentoxifylline was used in 6 rats; group 2 (acute lung injury group), only PMA was infused in 8 rats; group 3 (protective group), pentoxifylline 100 mg/300 g body weight was given intravenously before PMA infusion in 6 rats; group 4, only pentoxifylline was given in 6 rats. Pulmonary arterial pressure (PAP) as well as lung weight changes were recorded before and 5, 10, 15, 20 and 25 minutes after drug injection. Bronchial lavage fluids were then measured for albumin concentration. We found that PAP was strikingly increased in group 2 (54.0 +/- 8.8 mmHg), but the increase was significantly reduced in group 3 (29.8 +/- 5.8 mmHg, p less than 0.001). Similarly, the lung weight gain was markedly increased in group 2 (4.69 +/- 1.28 g), but was significantly attenuated in group 3 (1.25 +/- 1.60 g, p less than 0.001). There was no apparent change in PAP and lung weight gain throughout the entire procedure in groups 1 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Protective effect of pentoxifylline on phorbol myristate acetate-induced acute lung injury in rats. 198 33

Evidence has been accumulating that regulation of the rate of solute and fluid removal from the alveolar spaces may play an important role in the prevention and/or resolution of alveolar pulmonary edema. In this study, the isolated perfused rat lung was used to investigate the effects of an adenosine 3',5'-cyclic monophosphate (cAMP) analogue or a phosphodiesterase inhibitor on active sodium transport from airspace to vascular space. Three tracers were instilled into the airways of isolated Krebs-Ringer bicarbonate solution (KRB)-perfused rat lungs. The appearance of tracers in the single-pass perfusate was measured, and the apparent permeability-surface area products (PS) were calculated for each tracer at each sample time based on Fick's first law of diffusion. After steady-state PS values had been reached, a cAMP analogue or phosphodiesterase inhibitor was added to the perfusate. Both agents caused significant increases in the PS for 22Na. In another group of experiments, a cAMP analogue was added to the perfusate, followed by the subsequent addition of a sodium transport inhibitor and the resultant large decrease in the PS for 22Na. These data are consistent with the regulation of active sodium transport across the intact mammalian alveolar epithelium by a cAMP-mediated process leading to removal of sodium from the alveolar spaces, with anions and water following passively.
...
PMID:Evidence for regulation of sodium transport from airspace to vascular space by cAMP. 247 37

Lipid mediators of inflammation cause pulmonary edema, yet it is unclear to what degree hemodynamic alterations or increased vascular permeability contribute to lung edema formation. The isolated rat lung preparation was used to examine the effect of leukotriene C4 (LTC4) and platelet-activating factor (PAF) on pulmonary arterial pressure (Ppa), lung microvascular pressure (Pmv), lung wet-to-dry weight ratio, and the 125I-albumin escape index. We first defined the response of the isolated rat lung perfused with protein-free salt solution to hydrodynamic stress by raising the lung outflow pressure. Sustained elevation of the lung outflow pressure less than 5.5 cmH2O (4.01 mmHg) caused a negligible increase in Ppa and wet-to-dry lung weight ratio. Elevation of outflow pressures greater than 7.5 cmH2O (5.4 mmHg) increased the vascular albumin escape index more than the lung wet-to-dry weight ratio. Dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) inhibited the increase in albumin escape index because of increased lung outflow pressure, suggesting perhaps a pressure-independent microvascular membrane effect of db-cAMP. Both LTC4 (2-micrograms bolus) and PAF (2-2,000 ng/ml perfusate) increased the albumin escape index in association with increases in Ppa and Pmv. Because the increased albumin escape index after LTC4 or PAF injection was largely accounted for by the increased vascular pressures and because db-cAMP and papaverine inhibited the rise in vascular pressures and in the albumin escape index, we conclude that vasoconstriction is an important contributor to LTC4- and PAF-induced edema formation in rat lungs.
...
PMID:Importance of vasoconstriction in lipid mediator-induced pulmonary edema. 274 28

Acute, diffuse lung injury, the principal lesion in ARDS, is often refractory to treatment. Recently, pretreatment with several pulmonary vasodilators that increase cAMP levels: isoproterenol, terbutaline, theophylline, and prostacyclin, was found to reduce the severity of lung injury in animal models. We have investigated the possible modulation of HCl-induced pulmonary edema in rats by VIP, a lung neuropeptide with potent vasodilator and cAMP-producing properties. The lungs of rats were perfused in situ at 10 ml/min with Krebs-4% albumin solution, and ventilated at constant tidal volume (6.5 ml/kg). Peak airway pressure (PAW), mean pulmonary arterial pressure (PPA) were measured throughout the experiment, and wet to dry lung weight ratio (W/D), afterwards. All animals were observed for one hour. In 6 rats receiving HCl only, 0.2 N-HCl was instilled intratracheally at 2 ml/kg. Four rats received 2 ml/kg of physiological saline intratracheally as control. In 6 other animals, VIP was infused into the pulmonary artery at 1 micrograms/kg/min, beginning 10 minutes before HCl and for the rest of the experiment. Another 6 rats were pretreated with atrial natriuretic peptide (ANP, atriopeptin II) just like the VIP group. Lungs of saline control animals showed little or no chage in PAW or PPA. With HCl alone, PAW increased immediately and continued to rise for the rest of the hour, reaching 500% of basal value at 30 minutes. PPA increased by 68% and W/D by 74% compared to saline-instilled lungs. In the VIP + HCl group, all abnormalities were significantly reduced relative to the HCl group. The rise in PAW was attenuated by 79% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Vasoactive intestinal peptide (VIP) protects against acid-induced acute lung injury in isolated perfused rat lungs]. 281 Sep 67

There is a need for pharmacological agents for the treatment of pulmonary edema associated with the adult respiratory distress syndrome. Therefore, we examined the effects of isozyme-selective cyclic AMP phosphodiesterase (cAMP PDE) inhibitors, as well as aminophylline and dexamethasone, on the pulmonary edema, protein leakage into the airways and airway neutrophilia induced by aerosolized lipopolysaccharide (LPS) in intact guinea pigs. Twenty-four hours after LPS exposure lung wet/dry weight ratios increased from 4.9 +/- 0.004 to 5.8 +/- 0.02. Rolipram (PDE4 selective), CI-930 (PDE3 selective), aminophylline and dexamethasone (given p.o. 1 hr before and 4 hr after LPS exposure) inhibited pulmonary edema formation with ED50 values of 1.7, 0.5, 31 and 2.8 mg/kg, respectively. Maximum inhibition occurred with rolipram at 10 mg/kg (70 +/- 17%), CI-930 at 10 mg/kg (101 +/- 4%), aminophylline at 50 mg/kg (88 +/- 14%) and dexamethasone at 3 mg/kg (64 +/- 6%). Denbufylline and milrinone also inhibited pulmonary edema formation at 10 mg/kg i.p., supporting the inhibition of PDE4 and PDE3 as the mechanisms of action of rolipram and CI-930, respectively. Rolipram, CI-930, aminophylline and dexamethasone (at maximum doses for inhibiting pulmonary edema) inhibited the 3-fold increase in bronchoalveolar lavage albumin concentration 24 hr after LPS exposure (42 +/- 14%, 98 +/- 2%, 70 +/- 9% and 53 +/- 13%, respectively). However, none of these compounds (at maximum doses for inhibiting pulmonary edema) inhibited the corresponding 400-fold increase in lavage neutrophil counts.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Inhibition of lipopolysaccharide-induced pulmonary edema by isozyme-selective phosphodiesterase inhibitors in guinea pigs. 747 57

Neutrophil-derived hydrogen peroxide (H2O2) is believed to play an important role in the pathogenesis of vascular injury and pulmonary edema. H2O2 time- and dose-dependently increased the hydraulic conductivity and decreased the selectivity of an endothelial cell monolayer derived from porcine pulmonary arteries. Effects of H2O2 on endothelial permeability were completely inhibited by adenylate cyclase activation with 10(-12) M cholera toxin or 0.1 microM forskolin. 10(-8) M Sp-cAMPS, a cAMP-dependent protein kinase A agonist, was similarly effective. The phosphodiesterase (PDE) inhibitors motapizone (10(-4) M), rolipram (10(-6) M), and zardaverine (10(-8) M), which specifically inhibit PDE-isoenzymes III, IV, and III/IV potently blocked H2O2-induced endothelial permeability when combined with 10(-6) M prostaglandin E1. Overall cellular cAMP content and inhibition of H2O2 effects on endothelial permeability were poorly correlated. H2O2 exposure resulted in a rapid and substantial decrease in endothelial cAMP content. The analysis of the PDE isoenzyme spectrum showed high activities of isoenzymes II, III, and IV in porcine pulmonary endothelial cells. The data suggest that adenylate cyclase activation/PDE inhibition is a powerful approach to block H2O2-induced increase in endothelial permeability. This concept appears especially valuable when endothelial PDE isoenzyme pattern and PDE inhibitor profile are matched optimally.
...
PMID:Role of phosphodiesterases in the regulation of endothelial permeability in vitro. 838 87

The regulation of endothelial permeability is poorly understood. An increase in endothelial permeability in the pulmonary microvasculature, however, is critical in noncardiogenic pulmonary edema and other diffuse inflammatory reactions. In the present study thrombin and Escherichia coli hemolysin (HlyA), a membrane-perturbing bacterial exotoxin, were used to alter hydraulic permeability of porcine pulmonary artery and human endothelial cell monolayers. We also investigated the pharmacological approach of adenylyl cyclase activation/phosphodiesterase (PDE) inhibition to block endothelial hyperpermeability. Thrombin (1-5 units/ml) and HlyA (0.5-3 hemolytic units/ml) dose and time dependently (> 15 min) increased endothelial permeability. Forskolin, cholera toxin, and prostaglandin E1, which all stimulate adenylyl cyclase activity, abrogated this effect. One mM dibutyryl cAMP, a cell membrane-permeable cAMP analogue, was similarly active. Endothelial hyperpermeability was also reduced dose dependently by inhibitors of different PDE isoenzymes (motapizone, rolipram, and zardaverine, which block PDE3 and/or PDE4). The effectiveness of PDE inhibitors was increased in the presence of adenylyl cyclase activators. Analysis of cyclic nucleotide hydrolyzing PDE activity in lysates of human umbilical vein endothelial cells showed high activities of PDE isoenzymes 2, 3, and 4. Consistent with the functional data PDE3 and PDE4 were the major cAMP hydrolysis enzymes in intact endothelial cells. We conclude that the hyperpermeability of pulmonary endothelial monolayers, evoked by thrombin or HlyA, can be blocked by the simultaneous activation of adenylyl cyclase and inhibition of PDEs, especially of PDE3 and PDE4. The demonstration of PDE isoenzymes 2-4 in human endothelial cells will help optimize this therapeutic approach.
...
PMID:Hyperpermeability of pulmonary endothelial monolayer: protective role of phosphodiesterase isoenzymes 3 and 4. 883 Jan 94


1 2 3 4 5 6 Next >>

---