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

We studied the actions of saponin (ginsenosides) from Panax ginseng on free radical-induced pulmonary endothelial injury which is manifest as reversal of the normal vasodilator response to acetylcholine in perfused, vasoconstricted lungs. 50 or 200 micrograms/ml ginsenosides prevented this injury response and also reduced the pulmonary edema which follows free radical injury but did not alter the normal ACh-induced vasodilation in intact lungs. In control perfused lungs preconstricted with U46619, the ginsenoside mixture or purified ginsenosides Rb1 and Rg1 caused vasodilatation. This effect was eliminated by 100 microM nitro-L-arginine, an inhibitor of nitric oxide synthase. In cultured bovine aortic endothelial cells, ginsenosides (10 micrograms/ml) stimulated the conversion of [14C]-L-arginine to [14C]-L-citrulline. These data indicate that GS may cause vasorelaxation and prevent manifestations of oxygen free radical injury by promoting release of nitric oxide.
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PMID:Ginsenosides protect pulmonary vascular endothelium against free radical-induced injury. 147 38

Platelet-activating factor (PAF) causes pulmonary hypertension and lung edema in animals and isolated perfused lungs by poorly understood mechanisms. Because oxidative mechanisms have been implicated in PAF-mediated cellular injury, we tested the hypothesis that superoxide anion (O2-.) contributes to PAF-induced lung injury by determining whether superoxide dismutase (SOD) could prevent the lung injury. Isolated rabbit lungs were perfused with PAF (100 nM) at a dose that caused transient hypertension and mild edema. Lungs pretreated with Cu,Zn SOD (100 U/ml) for 10 min developed persistent pulmonary hypertension and more lung edema formation in response to PAF. Enhanced responses to PAF also were observed in lungs perfused with 200 U/ml Cu,Zn SOD, but not with 10 or 40 U/ml Cu,Zn SOD. The higher doses of SOD also decreased thromboxane B2 levels in the perfusate. Potentiation of the PAF effect by Cu,Zn SOD was eliminated if the enzyme was inactivated or if the lung was treated with an anion channel blocker. The augmented PAF response in the presence of SOD was not altered by catalase (200 U/ml) or by nitric oxide synthase inhibitor. The data suggest that excessive Cu,Zn SOD enzyme activity potentiates PAF-induced injury in perfused rabbit lung presumably by overscavenging extracellular O2.- generated from intercellular sources. The augmented responses to PAF are not directly attributable to increased hydrogen peroxide, nitric oxide-related products, or thromboxane A2 production. These results suggest the new hypothesis that a balance between O2-. production and its metabolism determines vascular and endothelial responses to PAF.
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PMID:Superoxide dismutase potentiates platelet-activating factor-induced injury in perfused lung. 751 30

At low concentrations, nitric oxide is a physiological transmitter, but in excessive concentrations it may cause cell and tissue injury. We report that in acute oxidant injury induced by the herbicide paraquat in isolated guinea pig lungs, nitric oxide synthesis was markedly stimulated, as evidenced by increased levels of cyclic GMP in lung perfusate and of nitrite and L-citrulline production in lung tissue. All signs of injury, including increased airway and perfusion pressures, pulmonary edema, and protein leakage into the airspaces, were dose-dependently attenuated or totally prevented by either NG-nitro-L-arginine methyl ester or N omega-nitro-L-arginine, selective and competitive inhibitors of nitric oxide synthase. Protection was reversed by excess L-arginine but not by its enantiomer D-arginine. When blood was added to the lung perfusate, the paraquat injury was moderated or delayed as it was when paraquat was given to anesthetized guinea pigs. The rapid onset of injury and its failure to occur in the absence of Ca2+ suggest that constitutive rather than inducible nitric oxide synthase was responsible for the stimulated nitric oxide synthesis. The findings indicate that nitric oxide plays a critical role in the production of lung tissue injury due to paraquat, and it may be a pathogenetic factor in other forms of oxidant tissue injury.
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PMID:Nitric oxide as a mediator of oxidant lung injury due to paraquat. 751 78

In the present study, we investigated the possible role of nitric oxide synthase in lung injury using female Fischer 344 rats as a model animal and O,O,S-trimethyl phosphorothioate as an example of lung toxicants. One form of nitric oxide synthase, Ca2+/calmodulin dependent type, decreased monotonously in a dose-dependent manner in the cerebellum. In contrast, O,O,S-trimethyl phosphorothioate increased activities of Ca2+ independent nitric oxide synthase in the lung in a dose-associated manner from 5 mg/kg to 15 mg/kg, but decreased at 30 mg/kg. Lung toxicity of O,O,S-trimethyl phosphorothioate, however, as judged both by functional impairments (PaCO2 and [HCO3-]) and histopathological changes, increased sharply at 30 mg/kg. We thus tested the hypothesis that a potent nitric oxide synthase inhibitor, NG-nitro-L-arginine-methyl ester, may modify lung injury induced by O,O,S-trimethyl phosphorothioate. Treatment with NG-nitro-L-arginine-methyl ester at 20 mg/kg/day aggravated lung injury induced by O,O,S-trimethyl phosphorothioate: Pulmonary oedema and bleeding occurred, leading to an increase in mortalities at 15 mg/kg of O,O,S-trimethyl phosphorothioate, at which level it did not induce such changes as when dosed alone. These findings indicate that nitric oxide synthase in the lung might play a protective role in lung injury.
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PMID:O,O,S-trimethyl phosphorothioate increases Ca2+ independent nitric oxide synthase activity in the lung but decreases Ca2+/calmodulin dependent type in the cerebellum in Fischer 344 rats. 752 78

The modulatory role of endogenous nitric oxide (NO) on pulmonary edema induced by acetylcholine (ACh), capsaicin, substance P (SP) and 5-hydroxytryptamine (5-HT) was investigated by using an inhibitor of NO synthase, N-omega-nitro-L-arginine (L-NNA). The effects of endogenous NO on the hemodynamic response to ACh, 5-HT and SP were also investigated. The capillary filtration coefficient (Kf,c), the total pressure gradient (delta Pt) and its four components [arterial (delta Pa), pre- (delta Pa') and post-capillary (delta Pv'), and venous gradient (delta Pv)] were evaluated on isolated, ventilated, perfused rabbit lungs. ACh (10(-8) to 10(-4) M) and SP (10(-10) to 10(-6) M) induced a concentration-dependent increase in the Kf,c. Capsaicin (10(-4) M) and 5-HT (10(-4) M) also increased this parameter. L-NNA (10(-4) M) completely inhibited the effects of ACh and capsaicin on the Kf,c, without preventing the effects of SP and 5-HT. ACh induced a concentration-dependent vasoconstriction in the precapillary segment. Pretreatment with L-NNA enhanced this increase in delta Pa' but also increased delta Pv' and delta Pv. 5-HT increased delta Pt and delta Pa proportionally to the concentration. This effect was enhanced by L-NNA, which also increased delta Pa'. SP had no significant hemodynamic effect. Pretreatment with L-NNA did not modify the response to SP. Sodium nitroprusside (10(-5) M) induced a left shift of the concentration-response curve to ACh on the Kf,c, although it did not change the response to SP. Sodium nitroprusside also inhibited the hemodynamic effect of ACh. It was concluded that endogenous NO is involved in ACh-and capsaicin-induced edema via a prejunctional stimulatory effect on the C-fibers. Endogenous NO can also modulate ACh- and 5-HT-induced vasoconstriction by exerting a vasodilator action on the whole pulmonary vascular bed.
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PMID:Endogenous nitric oxide modulates acetylcholine-induced edema and vasoconstriction in isolated perfused rabbit lungs. 754 68

Nitric oxide (NO) decreases cytotoxicity and proliferation of cytotoxic lymphocytes (CTLs) in vitro. Both can be prevented by inhibitors of the NO synthase (NOS). To elucidate whether inhibition of the IL-2-induced NOS could boost efficacy of IL-2-stimulated CTLs in vivo, we assessed lung metastases in mice injected with IL-2, the NOS inhibitor aminoguanidine (AG), their combination and the diluent. No improvement was observed for IL-2 + AG compared to IL-2 while NO production was normalized. Since NO causes one of the two major side effects of IL-2 treatment, hypotension, we further studied whether capillary leak could be attributed to NO, too. While IL-2-inducible NO was reduced to control levels by AG, pulmonary edema was unaffected. Thus a decrease in NO does not improve antitumor effects of IL-2-stimulated CTLs nor does it attenuate IL-2-associated capillary leak.
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PMID:Inhibition of nitric oxide synthesis does not improve interleukin-2-mediated antitumor effects in vivo. 873 27

The effect and mechanism of action of serotonin (5-HT) were studied in the pulmonary circulation of normal and diabetic rabbits. 5-HT (10, 50 and 100 nmol/l) produced a concentration-dependent increase in rabbit pulmonary arterial tension. Pulmonary arterial rings from diabetic rabbits were more responsive to 5-HT compared to those from normal rabbits. The pressor effects of 5-HT in normal and diabetic pulmonary arterial rings were totally abolished by either the 5-HT receptor antagonist, ketanserin (200 nmol/l) or the calcium channel blocker, verapamil (5.5 nmol/l). On the other hand, the cyclo-oxygenase inhibitor, indomethacin (0.4 nmol/l), significantly potentiated the pressor response of 5-HT in normal but not in diabetic pulmonary arterial rings. The lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA, 20 nmol/l), significantly enhanced the 5-HT-induced pressor response in normal rings while significantly attenuating those responses in diabetic rings. NG-nitro-L-arginine methyl ester (100 nmol/l), an inhibitor of nitric oxide synthase, significantly potentiated the contractile response of 5-HT in normal as well as diabetic pulmonary arterial rings. The results of this study indicate that 5-HT induces pulmonary hypertension in normal as well as in diabetic rabbits. In addition, experimentally induced diabetes exaggerates the pressor response of 5-HT and therefore may increase the risk of pulmonary hypertension. Furthermore, 5-HT alone or in combination with indomethacin, NDGA and a nitric oxide synthase inhibitor may be used to induce experimental pulmonary hypertension and possibly pulmonary edema.
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PMID:Hyperglycemia increased the responsiveness of isolated rabbit's pulmonary arterial rings to serotonin. 893 Nov

Previously, we showed that nitric oxide (NO) plays a major role in the pathogenesis of IL-2-induced capillary leak syndrome in healthy or mammary adenocarcinoma-bearing C3H/HeJ mice. NO synthase (NOS) inhibitors, such as NG-nitro-L-arginine methyl ester (L-NAME) reduced all the manifestations of IL-2-induced capillary leakage, without compromising the antitumor effects of IL-2. The present study was carried out on healthy C3H/HeJ mice subjected to one or two 4-day rounds of systemic IL-2 therapy with or without oral L-NAME therapy to: (a) identify the tissue source of NOS activity and NOS protein induced by IL-2 therapy; (b) identify histologically the nature of the structural damage to the lungs associated with IL-2 therapy-induced pulmonary edema; and (c) evaluate the effects of additional L-NAME therapy on the above-mentioned parameters. Results revealed that IL-2 therapy in healthy mice resulted in the expression of inducible NOS in numerous tissues including the endothelium and muscles of the anterior thoracic wall as well as splenic macrophages. One round of IL-2 therapy resulted in high levels of inducible NOS (iNOS) activity in the anterior thoracic wall accompanied by pleural effusion. After two rounds of IL-2 therapy, there was neither pleural effusion nor high iNOS activity in the thoracic wall. IL-2-induced pulmonary edema after one round of therapy correlated to both a significant rise in NO production measured in the serum and structural damage to the lungs and its capillaries. Addition of the NOS inhibitor L-NAME totally eradicated NOS activity but not necessarily iNOS expression. It also reduced IL-2-induced pulmonary edema and pleural effusion, restrained the rise in the levels of NO metabolites (nitrites and nitrates) in the serum and pleural effusion, and significantly restored the structural integrity of the lungs after one round of therapy. Thus, NOS inhibitors may be beneficial adjuncts to IL-2 therapy for cancer and infectious diseases.
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PMID:The role of active inducible nitric oxide synthase expression in the pathogenesis of capillary leak syndrome resulting from interleukin-2 therapy in mice. 901 Apr 49

This study was designed to investigate the possible participation of the L-arginine-nitric oxide (NO) pathway in the lung oedema induced by alpha-naphthylthiourea, which is a well-known noxious chemical agent in the lung. Lung oedema was assessed by measuring fluid accumulation in the pleural cavity and the lung weight/body weight ratio following alpha-naphthylthiourea injection. Administration of NG-nitro-L-arginine methyl ester, a NO synthase inhibitor, prior to alpha-naphthylthiourea, produced a significant inhibition of pleural effusion and lung weight/body weight ratio in a dose-dependent manner. L-Arginine, but not D-arginine, when used higher doses (above 300 mg/kg) prior to alpha-naphthylthiourea injection caused a significant inhibition of pleural effusion without altering lung weight/body weight ratio. Lower doses of L-arginine (below 100 mg/kg) did not elicit an inhibitory effect against alpha-naphthylthiourea-induced pulmonary damage. However, lower doses of L-arginine greatly potentiated the inhibitory effect of NG-nitro-L-arginine-methyl ester against alpha-naphthylthiourea-induced lung oedema when used in combination. The interesting aspect of this study is the inhibition by NG-nitro-L-arginine methyl ester, a NO synthase inhibitor, and L-arginine, an endogenous donor of NO, of the lung oedema induced by alpha-naphthylthiourea. The possible role of the L-arginine-NO pathway in lung oedema induced by alpha-naphthylthiourea and the possible underlying mechanisms are discussed.
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PMID:An unexpected interaction between NG-nitro-L-arginine methyl ester and L-arginine in alpha-naphthylthiourea-induced pulmonary oedema in rats. 908 85

We examined the effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), on mortality, morbidity, and cardiovascular parameters following traumatic brain injury (TBI) in the rat. Rats were anesthetized with 2% isoflurane prior to moderate (2.0 atmosphere), central fluid percussion TBI. Temporalis muscle temperature was maintained at 37 +/- 0.5 degrees C. L-NAME (10 mg/kg iv) was administered once at either 5 min before, 5 min after, or 15 min after TBI. Sensorimotor deficits and spatial learning/ memory deficits were assessed after injury. Separate groups of rats were monitored for cardiovascular parameters. Preinjury administration of L-NAME significantly increased mortality from 13 (vehicle) to 70% (associated with pulmonary edema), whereas postinjury, L-NAME had no effect on mortality (14 and 25%). L-NAME administered at 5 or 15 min after injury had no significant effect on motor performance or cognitive performance deficits associated with TBI. L-NAME in uninjured rats increased arterial blood pressure by 25 mmHg within 2 min. L-NAME injected 5 min before TBI greatly prolonged the hypertensive episode associated with TBI (1 min in vehicle vs 60 min in L-NAME). L-NAME injected 5 min after TBI caused a sustained 35 mmHg increase in blood pressure. These findings suggest that acute inhibition of NOS has detrimental consequences on mortality that may be owing to its cardiovascular effects.
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PMID:Inhibition of nitric oxide synthase potentiates hypertension and increases mortality in traumatically brain-injured rats. 913 24


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