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)

Changes in pulmonary endothelial permeability and in microvascular hemodynamics in response to cumulative concentrations of acetylcholine (ACh) (10(-8) M to 10(-5) M) were investigated in isolated, perfused rabbit lungs. The total pressure gradient was partitioned into four components: arterial, pre- and postcapillary and venous. The capillary filtration coefficient (Kf, c) also was evaluated. ACh caused a significant increase in arterial and precapillary pressures at concentrations higher than 3 x 10(-6) M. The total pressure gradient and precapillary were significantly increased whereas arterial, postcapillary and venous pressure gradient remained unchanged. In papaverine (3 x 10(-4) M)-pretreated lungs, the vasoconstriction was abolished and a concentration-dependent increase in Kf,c was recorded from 10(-8) to 10(-5) M ACh. This reaction was accompanied by pulmonary edema. Atropine, indomethacin, aspirin, ketanserin, clonidine, morphine and (+/-)-CP 96-345, an antagonist of neurokinin NK1 receptors, completely prevented the effects of ACh on Kf,c. In contrast, cromolyn sodium and SR48968, a neurokinin NK2 antagonist, did not inhibit the response to ACh. Terfenadine together with cimetidine had a partially inhibitory effect. Changes in the Kf, c similar to those observed with ACh were induced by capsaicin (10(-4) M) by exogenous substance P (10(-7) M) and by 5-hydroxytryptamine (5-HT) (10(-4) M). The effects of SP were inhibited by aspirin, (+/-)-CP 96,345 and ketanserin, but not by atropine and antihistaminics. 5-HT effects were prevented by aspirin and not by (+/-)-CP 96,345. It was concluded that ACh-induced pulmonary edema was due to an increase in the capillary filtration coefficient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of neuropeptides in acetylcholine-induced edema in isolated and perfused rabbit lungs. 768 2

Protease-activated receptors (PARs) and tachykinin-immunoreactive fibers are located in the lung as sentries to respond to a variety of pathological stimuli. The effects of PAR activation on the lung have not been adequately studied. We report on the effects of instilling PAR-activating peptides (PAR-APs, including PAR1-, PAR2-, and PAR4-AP) into the lungs of ventilated or spontaneously breathing mice. PAR2-AP, but not PAR1-AP or PAR4-AP, caused a sharp increase in lung endothelial and epithelial permeability to protein, extravascular lung water, and airway tone. No responses to PAR2-AP were detected in PAR2 knockout mice. In bronchoalveolar lavage, PAR2 activation caused 8- and 5-fold increase in MIP-2 and substance P levels, respectively, and a 12-fold increase in the number of neutrophils. Ablation of sensory neurons (by capsaicin) markedly decreased the PAR2-mediated airway constriction, and virtually abolished PAR2-mediated pulmonary inflammation and edema, as did blockade of NK1 or NK2 receptors. Thus, PAR2 activation in the lung induces airway constriction, lung inflammation, and protein-rich pulmonary edema. These effects were either partly or completely neuropeptide dependent, suggesting that PAR2 can cause lung inflammation by a neurogenic mechanism.
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PMID:Protease-activated receptor-2 activation induces acute lung inflammation by neuropeptide-dependent mechanisms. 1608 34

Neurotensin, a bioactive tridecapeptide, has been shown to regulate inflammatory process in lung tissues. However, the effect of neurotensin on LPS-induced lung injury and underlying detailed molecular mechanisms has not been studied. The aim of present study is to investigate the effect of neurotensin on LPS-induced acute lung injury in mice. Mice were treated with LPS intratracheally to induce acute lung injury. 1 hour after ALI induction, and then mice were treated with neurotensins (NTs) (20 mg/kg, 40 mg/kg, and 80 mg/kg) via tail vein injection. Next, the severity of lung injury, MPO activity, neutrophils infiltration, lung edema, protein and pro-inflammatory cytokines concentration in BALF were determined to evaluate the effect of Nts on ALI. Additionally, the expression of tachykinins receptors, including NK1, NK2, and NK3 and the production of IL-8, COX-2, and PGE2 mediated by tachykinins-tachykinins receptors pathway were determined to investigate the blocking effect of Nts on tachykinins and its receptors pathway. Neurotensins treatment significantly decreased the lung edema and the infiltration of inflammatory cells into lung tissue caused by LPS induction. Meanwhile, the elevation of pro-inflammatory cytokines and chemokine in BALF was dramatically reduced by neurotensins treatment. Furthermore, neurotensins could interact with tachykinins receptors and block the inflammatory responses activated by tachykinins pathways. In summary, neurotensins has a potentially protective effect on LPS-induced acute lung injury through the interaction with tachykinins receptors and subsequently blocking the inflammatory responses induced by activation of tachykinins pathway.
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PMID:Protective effects of neurotensins on lipopolysaccaride-induced acute lung injury by blocking tachykinin mediated pathway. 3196 69