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)

Smoking increases plasma levels of thromboxane (Tx) B2. Since intravenous nicotine is without effect on platelet TxB2 synthesis, it is likely that lung parenchyma is the site of metabolic importance. This study examines the TxB2 response and functional consequences to the lungs of intratracheal and intravenous instillations of nicotine tartrate. Rat lungs perfused with Krebs-Henseleit (K-H) solution without recirculation were used. After hemodynamic stabilization, the perfusate was either left unaltered or switched to 5 X 10(-4) M nicotine. After 20 minutes of K-H perfusion, effluent levels of TxB2 fell from 41 +/- 6 pg/ml (mean +/- standard error) to 16 +/- 5 pg/ml. A similar decline was noted with nicotine perfusion. K-H perfusion was used throughout the second set of experiments. The lungs were instilled with either saline solution (1 ml/kg body weight) or 5 X 10(-4) M nicotine in saline solution. In the nicotine group, TxB2 levels rose to 86 +/- 5 pg/ml versus 22 +/- 3 pg/ml in saline-instilled controls (p less than 0.05). In addition, pulmonary edema developed in nicotine-instilled lungs. Pretreatment with the Tx synthase inhibitor OKY-046 prevented the rise in TxB2 concentration after nicotine instillation and led to a wet weight/dry weight ratio of 4.0 +/- 0.4 versus 7.5 +/- 1.5 in untreated control lungs (p less than 0.05). Pretreatment with the lipoxygenase inhibitor diethylcarbamazine increased TxB2 levels to 235 +/- 34 pg/ml (p less than 0.05). Diethylcarbamazine also lowered pulmonary artery pressure from 18 +/- 1 mm Hg to 6.1 +/- 0.7 mm Hg in control lungs (p less than 0.05) but did not reduce edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Nicotine stimulates pulmonary parenchymal thromboxane synthesis. 377 53

It is known that reactive oxygen species cause lung injury in association with activation of arachidonate metabolism. Because metabolites of the cyclooxygenase pathway do not appear to mediate the injury, we considered that the 5-lipoxygenase pathway might be activated and that inhibition of the pathway could interfere with the development of the injury. Thus, we sought to induce an oxidant lung injury and to prevent such injury by inhibiting lipoxygenase pathway or by blocking leukotriene action. In isolated rat lungs, glucose oxidase added to a glucose-containing, cell-free perfusate was used to produce the injurious oxygen species. Lung edema occurred and increased with increasing oxygen tension in the inspired air. Light microscopy of the lung showed perivascular fluid cuffs, and electron microscopy showed endothelial cell damage. Measurements in the lung effluent showed that concentrations of 5-hydroxyeicosatetraenoic acid (5-HETE) and of cyclooxygenase metabolites increased after glucose oxidase administration; BW 755C, U60,257, and FPL 55712 inhibited the glucose-oxidase-induced lung edema. And U60,257 also inhibited the glucose-oxidase-induced increase in 5-HETE without concomitant inhibition of cyclooxygenase metabolites. Thus, glucose oxidase via generation of active oxygen species stimulated the lung 5-lipoxygenase pathway, and inhibitors of 5-lipoxygenase protected against the oxidant lung injury. Further, in these experiments, the injury occurred in the absence of circulating blood cells and was augmented by increasing the inspired oxygen concentration.
...
PMID:Leukotriene inhibitors attenuate rat lung injury induced by hydrogen peroxide. 392 81

We describe neutrophil chemoattractant activity that is produced by cultured bovine aortic and pulmonary arterial endothelial cells when incubated with thiourea, a substance that causes increased permeability pulmonary edema in animals. The chemoattractant activity was present in culture supernates and cell lysates of endothelial cells incubated with thiourea but was not present in untreated cells. Production of chemoattractant activity was not associated with cell death; viable cell counts and cell homogenate angiotensin converting enzyme levels were not affected, and Cr release was only slightly elevated after incubation with thiourea. At least 1.5 h of incubation with 0.5 mM thiourea was necessary for generation of neutrophil chemoattractant activity. Culture supernates from pulmonary vascular smooth muscle cells and lung fibroblasts did not show increased neutrophil chemoattractant activity after incubation with thiourea. The chemoattractant had both chemokinetic and chemotactic properties, was heat stable, and was extractable into organic solvents. Meclofenamate, a cyclooxygenase inhibitor, minimally inhibited chemoattractant production, whereas 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of both cyclooxygenase and lipoxygenase, completely abolished generation of chemoattractant activity, suggesting that the activity could be a product of arachidonic acid metabolism. These results demonstrate that endothelial cells can produce a substance(s) with neutrophil chemotactic activity. Production of neutrophil chemoattractant activity by endothelial cells could be important in polymorphonuclear leukocyte accumulation at injured vascular sites.
...
PMID:Thiourea causes endothelial cells in tissue culture to produce neutrophil chemoattractant activity. 643 Jan 36

The possible contribution of metabolites of arachidonic acid to the increased permeability of the alveolar-capillary barrier in the adult respiratory distress syndrome was examined by quantifying the pulmonary edema fluid concentrations of lipoxygenase and cyclooxygenase products. The concentration of leukotriene D4 in pulmonary edema fluid of 10 patients with the adult respiratory distress syndrome (18.5 +/- 6.8 pmol/ml; mean +/- SD), assessed by specific radioimmunoassay after isolation of the mediator, was significantly higher (P less than 0.001) than that of five patients with cardiogenic pulmonary edema (4.4 +/- 1.1 pmol/ml). The concentrations of leukotrienes B4 and C4, prostaglandin E2, and thromboxane B2 in edema fluid were not significantly different in the adult respiratory distress syndrome patients than in the other subjects with pulmonary edema. The edema fluid concentration of leukotriene D4 correlated with the ratio of edema fluid to plasma concentrations of albumin (r = 0.64). Leukotriene D4 thus may contribute to the permeability defect which allows an accumulation of protein-rich alveolar fluid in the adult respiratory distress syndrome.
...
PMID:Elevated concentrations of leukotriene D4 in pulmonary edema fluid of patients with the adult respiratory distress syndrome. 651 65

The adult respiratory distress syndrome is pulmonary edema with low heart pressures and hypoxemia. Based on experimental models of the human disease, it is likely that functional injury to the lung includes pulmonary vasoconstriction, a loss of hypoxic vasoconstriction, increases in resistance to airflow across the lungs, decreases in lung compliance (perhaps both resulting from airway constriction), and lung microvascular injury resulting in pulmonary edema. Data accumulated over the last several years strongly suggest an important role for both cyclo-oxygenase metabolites and lipoxygenase metabolites of arachidonic acid in mediating lung vascular injury in this syndrome. Likewise, more recent evidence suggests a causative role for granulocytes in mediating the lung injury. Based on what is known about the biological activity of products of granulocytes and metabolites of arachidonic acid, it is reasonable to hypothesize a sequence of events in which arachidonate metabolites and granulocytes interact to result in pulmonary vasoconstriction, loss of hypoxic vasoconstriction, airway responses and capillary injury. It remains possible, perhaps even likely, that other humoral mediators, platelets and perhaps even other cellular mediators (for example, mast cells or lymphocytes) participate in the pathogenic sequence of events in ARDS. Specific delineation of the mechanisms of lung injury in this syndrome must await further research.
...
PMID:Mechanisms of lung injury. 680 59

Liberation and metabolism of arachidonic acid may be the common final pathway of different stimuli on the pulmonary vascular bed. In a model of isolated, ventilated rabbit lungs, perfused with Krebs Henseleit albumin buffer in a recirculating system, changes of pulmonary vascular resistance and of vascular permeability are monitored continuously. The addition of free arachidonic acid or of the Ca-ionophore A 23187 to the perfusion fluid consistently evokes a biphasic increase in vascular resistance as well as an initially reversible increase in vascular permeability, followed by pulmonary edema. Both phases of increased vascular resistance are completely suppressed by inhibition of the cyclooxygenase, decreased to a large degree by inhibitors of thromboxane synthetase, and markedly augmented by short preincubation of arachidonic acid with ram seminal vesicular microsomes and by sulfhydryl reagents. The increased pulmonary vascular permeability is augmented by inhibition of cyclooxygenase and reduced by simultaneous lipoxygenase inhibition. Antagonists of histamine, serotonin and sympathic or parasympathic activity do not have any influence. PG F2alpha., TxB2, PG E2 and PG I2 alter the pulmonary vascular resistance, but do not increase vascular permeability. In conclusion, increased availability of free arachidonic acid evokes a rise in pulmonary vascular resistance, which can be ascribed to cyclooxygenase products, especially to thromboxane, and causes a rise in vascular permeability which can be ascribed to lipoxygenase products. The findings may be related to acute pulmonary lesions with increase in vascular resistance and with vascular leakage.
...
PMID:Increased pulmonary vascular resistance and permeability due to arachidonate metabolism in isolated rabbit lungs. 680 41

Release and metabolism of arachidonic acid are supposed to form the common final pathway of different stimuli on the pulmonary vascular endothelium. In a model of isolated, ventilated and perfused rabbit lungs we investigated the influence of increased availability of free arachidonic acid on pulmonary vascular resistance and permeability. Addition of arachidonic acid to the perfusion fluid or release of arachidonic acid by Ca-ionophore A 23187 regularly produces a characteristic biphasic increase of the pulmonary vascular resistance as well as a continuous increase in permeability, followed by pulmonary edema. Inhibition of cyclooxygenase by indomethacin prevents the augmentation of vascular resistance, the increase of vascular permeability however is enhanced. thus the raise in pulmonary vascular resistance can be ascribed to cyclooxygenase products, the increased pulmonary vascular permeability to lipoxygenase products of arachidonic acid.
...
PMID:[Increase of pulmonary vascular resistance and permeability due to the metabolism of free arachidonic acid (author's transl)]. 727 87

Pulmonary edema following smoke inhalation is due to the chemical toxins in smoke and not to the heat. We have shown that acrolein, a common component of smoke, induces pulmonary edema, perhaps via release of leukotrienes. We, therefore, hypothesized that acrolein, a component of smoke from burning cotton, might have a major role in producing pulmonary edema in sheep after cotton smoke inhalation and that BW-755C, a combined cyclo- and lipoxygenase inhibitor, would prevent the edema, whereas indomethacin, a cyclooxygenase inhibitor, would not. In control anesthetized sheep (n = 7), 128 breaths of cotton smoke induced no change in pulmonary arterial pressure but induced increases (P < 0.05) in pulmonary lymph flow from 4.4 +/- 0.8 (SE) to 15 +/- 2.7 ml/h, lymph protein flux from 0.25 +/- 0.08 to 0.80 +/- 0.16 g/h, and blood-corrected wet-to-dry weight ratios from a normal value of 3.8 +/- 0.07 (n = 9) to 4.5 +/- 0.18. Indomethacin (n = 6) did not significantly prevent these changes, whereas BW-755C decreased lung lymph flow change from 5 +/- 1 to 7 +/- 2 ml/h (P = NS), lymph protein flux from 0.25 +/- 0.08 to 0.35 +/- 0.1 g/h (P = NS), and weight-to-dry ratio from normal to 3.9 +/- 2.1 (P = NS). These data suggest leukotrienes may have a role in producing cotton smoke-induced noncardiogenic pulmonary edema.
...
PMID:BW-755C diminishes smoke-induced pulmonary edema. 771 45

Inhalation of smoke containing acrolein, the most common toxin in urban fires after carbon monoxide, causes vascular injury with non-cardiogenic pulmonary edema containing potentially edematogenic eicosanoids such as thromboxane (Tx) B2, leukotriene (LT) B4, and the sulfidopeptide LTs (LTC4, LTD4, and LTE4). To determine which eicosanoids are important in the acute lung injury, we pretreated sheep with BW-755C (a combined cyclooxygenase and lipoxygenase inhibitor), U-63557A (a specific Tx synthetase inhibitor), or indomethacin (a cyclooxygenase inhibitor) before a 10-min exposure to a synthetic smoke containing carbon particles (4 microns) with acrolein and compared the results with those from control sheep that received only carbon smoke. Acrolein smoke induced a fall in arterial PO2 and rises in peak inspiratory pressure, main pulmonary arterial pressure, pulmonary vascular resistance, lung lymph flow, and the blood-free wet-to-dry weight ratio. BW-755C delayed the rise in peak inspiratory pressure and prevented the fall in arterial PO2, the rise in lymph flow, and the rise in wet-to-dry weight ratio. Neither indomethacin nor U-63557A prevented the increase in lymph flow or wet-to-dry weight ratio, although they did blunt and delay the rise in airway pressure and did prevent the rises in pulmonary arterial pressure and pulmonary vascular resistance. Thus, cyclooxygenase products, probably Tx, are responsible for the pulmonary hypertension after acrolein smoke and to some extent for the increased airway resistance but not the pulmonary edema. Prevention of high-permeability pulmonary edema after smoke with BW-755C suggests that LTB4, may be etiologic, as previous work has eliminated LTC4, LTD4, and LTE4.
...
PMID:Cyclooxygenase and lipoxygenase inhibition by BW-755C reduces acrolein smoke-induced acute lung injury. 800 44

Platelet-activating factor (PAF) is a cell membrane-derived ether lipid that plays an important role in acute lung vascular injury. We recently reported that PAF potentiates protamine-induced lung edema by enhancing pulmonary venoconstriction. As PAF is known to stimulate lung eicosanoid synthesis, we investigated the role of peptidoleukotrienes and other eicosanoids in this priming effect of PAF. Addition of PAF (1.6 nM), followed 10 min later by protamine (50 micrograms/ml), to perfusate of salt solution-perfused rat lungs resulted in marked arterial and venous constrictions and severe lung edema. Lung tissue thromboxane B2, 6-ketoprostaglandin F1 alpha and leukotriene C4 (LTC4) were markedly elevated 20 min after PAF/protamine. Pretreatment of the lungs with AA-861, a specific 5-lipoxygenase inhibitor, blocked PAF/protamine-induced leukotriene synthesis, arterial and venous constrictions, and lung edema. In addition, injection of LTC4 (1 microgram) markedly potentiated protamine-induced arterial and venous constrictions and caused lung edema similar to PAF/protamine. Indomethacin, a specific cyclooxygenase inhibitor, also reduced the vasoconstrictive and edemagenic responses to PAF/protamine. However, the pulmonary edema after LTC4/protamine was not blocked by indomethacin. In separate experiments, infusion of this "priming" dose of PAF into isolated perfused lungs induced LTC4 synthesis and augmented lung thromboxane A2 synthesis after arachidonic acid infusion. We conclude that both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism are involved in PAF-induced potentiation of protamine lung edema.
...
PMID:Platelet-activating factor potentiates protamine-induced lung edema. Role of eicosanoids. 811 95


<< Previous 1 2 3 4 Next >>

---