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)

Most recently we have shown that 4-aminotetrahydrobiopterin (4-ABH4), an analogue of tetrahydrobiopterin (cofactor of NO synthase), even administered 2 h after endotoxin challenge, improves survival rate in rats. The following experiment was performed to examine the effects of 4-ABH4 with respect to endotoxin-induced hemodynamic alterations and organ failure. At 2 h after endotoxic challenge (10 mg kg(-1) body weight) animals received 4-ABH4 at a dose of 1, 10, or 100 mg kg(-1) body weight. The controls were treated similarly but received saline at the same volume. Eight hours after endotoxin challenge cardiac index and stroke volume were significantly increased in animals treated with 10 mg 4-ABH4 compared to controls (0.23 +/- 0.06 vs. 0.16 +/- 0.04 mL min(-1) kg(-1) and 0.29 +/- 0.05 vs. 0.22 +/- 0.03 mL beat(-1)) while mean arterial pressure and peripheral vascular resistance index did not significantly differ among the groups. Plasma alanine aminotransferase (ALT) and creatinine levels were significantly increased in endotoxin controls compared with laboratory controls (ALT: 1643 +/- 1436 vs. 74 +/- 17 U L(-1); Creatinine: 91 +/- 29 vs. 42 +/- 3 micromol L(-1)) which was attenuated in animals treated with 10 mg kg(-1) 4-ABH4 (ALT: 417 +/- 318 U L(-1); Creatinine: 78 +/- 26 micromol L(-1)). Moreover, endotoxin-induced lung edema and intestinal necrosis were significantly reduced by 4-ABH4. Our study provides information that tetrahydrobiopterin analogue, 4-ABH4, improves LPS induced hemodynamic conditions and organ injury. This may, at least in part, account for the previously observed protection of rats by 4-ABH4 against endotoxin-induced mortality in the same endotoxic shock model.
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PMID:A 4-amino analogue of tetrahydrobiopterin attenuates endotoxin-induced hemodynamic alterations and organ injury in rats. 1216 80

The first limiting factor of dietary zinc deficiency has been described as a loss of the protective role of zinc against auto-oxidation of membrane sulfhydryl (SH) compounds. It has now been established that the prohormones (nutriuretic peptides) of the intestinal guanylin family are activated extracellularly by conversion of cysteines in the peptide to disulfide bridges. The induction of uroguanylin mRNA is elevated in intestinal zinc deficiency and nutriuretic peptides regulate epithelial transport of salt and water. Nitric oxide (NO) is also a modulator of salt and water transport. The constitutive forms of nitric oxide synthase (cNOS) in neurons and endothelial cells are calcium-dependent. The inducible form of nitric oxide synthase (iNOS) is activated by bacterial entero-toxins and damaged mucosa with NO penetrating the cell and acting directly on guanylate cyclase. The activated receptor-guanylate cyclases initiating the intracellular cycle 3'-5' guanasine monophosphate (cyclic GMP) cascade in target cells results in a flux of chloride and water into the intestinal lumen. Most of the actions of NO are mediated by activation of cyclic GMP. High-altitude pulmonary edema (HAPE) is associated with a defect in transepithelial water transport. It is suggested that dietary zinc, by modulating thiol oxidation to disulfides in guanylin prohormones to active hormones, is associated with salt and water secretion such that the overworked heart in hypoxemia increases the production and release of natriuretic peptides to activate guanylate cyclase receptors in target tissue in sudden infant death syndrome.
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PMID:Sudden infant death syndrome: is it a transepithelial transport disorder? 1232 27

In the course of investigations on mechanisms underlying development of neurogenic pulmonary edema (NPE), we have evaluated effects of nitric oxide (NO) in the central nervous system on incidence and severity in the fibrin-induced pulmonary edema model. Rats left-unilaterally vagotomized 1, 2 and 4 weeks before injections of fibrinogen and thrombin into the cisterna magna, after cutting the right vagus nerve, grouped as LVIW, LV2W or LV4W, respectively. The brain NO synthase (NOS) mRNA level in the left medulla oblongata was elevated in the LV2W group, compared to the control, but decreased in the LV4W rats. Incidences of pulmonary edema were 100% in the control group, decreasing to 78% in LV1W group, 17% in LV2W group, and back to 72% in LV4W group. The lung water ratio, a parameter of severity, demonstrated a similar pattern of change as the incidence. The lowered incidence and severity obtained in the LV2W group were reversed by intracisternal injection of N-nitro-L-arginine methyl ester (L-NAME). From these results, we propose that an increase in nitric oxide, possibly in the nucleus tractus solitarius 2 weeks after left vagotomy, may have an inhibitory action on the development of neurogenic pulmonary edema in rats.
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PMID:Inhibition of fibrin-induced neurogenic pulmonary edema by previous unilateral left-vagotomy correlates with increased levels of brain nitric oxide synthase in the nucleus tractus solitarii of rats. 1249 29

Congestive heart failure results in cardiovascular dysfunction and diminished vascular nitric oxide (NO) production. We hypothesized that overexpression of endothelial NO synthase (eNOS) within the endothelium would reduce the extent of contractile dysfunction in a murine model of infarct-induced congestive heart failure. We generated transgenic (TG) mice overexpressing the human eNOS gene. The TG mice displayed significantly enhanced eNOS protein levels and eNOS activity levels (10- to 12-fold greater) in the aorta and the coronary vasculature. Non-TG (NTg) and eNOS TG mice were subjected to permanent left anterior descending coronary artery occlusion and then observed for 1 mo. We assessed cardiac function in vivo by using echocardiography and ultraminiature ventricular pressure catheters. Myocardial infarct size was similar between study groups (approximately 70% of the risk zone). Survival was increased by 43% in the eNOS TG mice compared with NTg (P < 0.05). Fractional shortening and cardiac output were also significantly (P < 0.05) greater in the eNOS TG than in NTg. Interestingly, pulmonary edema was evident only in NTg mice, and no evidence of pulmonary edema was observed in the eNOS TG mice. Thus, targeted overexpression of the eNOS gene within the vascular endothelium in mice attenuates both cardiac and pulmonary dysfunction and dramatically improves survival during severe congestive heart failure.
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PMID:Endothelial nitric oxide synthase overexpression attenuates congestive heart failure in mice. 1267 84

Acute respiratory distress syndrome (ARDS) can be associated with various disorders. Among these, coronavirus infection may cause life-threatening severe acute respiratory syndrome (SARS). In this review, we present animal models and techniques for the study of ARDS, and discuss the roles and possible mechanisms of various chemical factors, including nitric oxide (NO). Our early work revealed that cerebral compression elicits severe hemorrhagic pulmonary edema (PE), leading to central sympathetic activation that results in systemic vasoconstriction. The consequence of systemic vasoconstriction is volume and pressure loading in the pulmonary circulation. Vasodilators, but not oxidant radical scavengers, are effective in the prevention of centrogenic PE. In isolated perfused lung, exogenous and endogenous NO enhances lung injury following air embolism and ischemia/reperfusion. In contrast, NO synthase (NOS) inhibitors reverse such lung injury. Although NO is important in maintaining vasodilator tone, hypoxia-induced pulmonary vasoconstriction is accompanied by an increase instead of a decrease in NO release. In animal and isolated lung studies, endotoxin produces acute lung injury that is associated with increases in cytokines and inducible NOS mRNA expression, suggesting that NO is toxic to the lung in endotoxin shock. Recently, we reported several rare cases that indicate that ARDS in patients with Japanese B encephalitis, lymphangitis with breast cancer and fat embolism is caused by different mechanisms. Our early and recent studies on ARDS and PE may provide information for clinical practice and the understanding of the pathogenesis of SARS.
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PMID:Acute respiratory distress syndrome. 1457 60

High-altitude pulmonary oedema (HAPE) is a potentially fatal condition affecting fit and previously well individuals at altitudes in excess of 3000 m. This article discusses the mechanisms of HAPE, considers the contribution of hypoxic pulmonary vasoconstriction and alterations in sodium transport to the pathological process. It discusses the various biochemical mediators such as nitric oxide (NO), endothelin-1 (ET-1), and the renin-angiotensin-aldosterone system (RAS) that may be involved and considers possible oxygen-sensing mechanisms involved in hypoxic adaptation such as hypoxia-inducible factor-1 (HIF-1). Those who have had HAPE once run an unpredictable but significant risk of recurrence; therefore, there may be a constitutional or genetic component in its aetiology. This paper considers the possible involvement of genes that may be involved in physiological adaptation to hypoxia (e.g., angiotensin-1 [AT(1)]-converting enzyme [ACE], tyrosine hydroxylase, serotonin transporter [5-HTT], and endothelial NO synthase [eNOS] genes). As yet, no formal association has been identified between an identified genetic polymorphism and HAPE, but genetic variation provides a possible mechanism to explain interindividual variation in response to hypoxia and enhanced or reduced performance at altitude.
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PMID:The genetic basis of high-altitude pulmonary oedema. 1476 4

Endogenous nitric oxide (NO) is known to modulate post-ischemic inflammatory response in various organs. However, the role of nitric oxide synthase isoforms (NOS) in mediating pulmonary post-ischemic inflammatory response is poorly understood. We therefore studied post-ischemic endothelial adhesion molecule expression and leukocyte migration in endothelial NOS knockout (eNOS-KO) mice subjected to pulmonary ischemia and reperfusion in vivo. Under anesthesia and mechanical ventilation, the left pulmonary hilum in wild-type (WT) and eNOS-KO mice was clamped for 1 hour, followed by reperfusion for up to 24 hours. In WT mice, we observed a selective up-regulation of both eNOS mRNA and protein in lung tissue, while inducible NOS (iNOS) and neuronal NOS (nNOS) remained unchanged. Survival in eNOS-KO mice was reduced due to severe pulmonary edema, underlining an increased susceptibility to ischemia-reperfusion (I/R) injury. Interstitial tissue infiltration by CD18- and CD11a-positive white blood cells as well as lung tissue water content peaked at 5 hours of reperfusion and were found significantly higher than in WT mice. Enhanced leukocyte-endothelial interaction was associated with pronounced up-regulation of vascular cell adhesion molecule (VCAM) in eNOS-KO mice during post-ischemic reperfusion. We conclude that eNOS attenuates post-ischemic inflammatory injury to the lung most probably via inhibition of endothelial adhesion molecule expression.
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PMID:Up-regulation of endothelial nitric oxide synthase inhibits pulmonary leukocyte migration following lung ischemia-reperfusion in mice. 1516 56

The primary goal of this study was to determine whether Tx2-5, a sodium channel selective toxin obtained from the venom of the spider Phoneutria nigriventer, produced penile erection by means of nitric oxide mechanism. Toxin identity was analyzed by MALDI-TOF, ES-MS and N-terminal amino acid sequencing. Pretreating mice with the non-selective nitric oxide synthase (NOS) inhibitor N(omega)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and the selective neuronal-NOS inhibitor 7-Nitroindazole (7-NI) prior to Tx2-5 i.p. (10 microg/25 g mouse) injection challenged the hypothesis above. Controls were injected with the D-isomer or DMSO or saline. Results demonstrated that L-NAME inhibited penile erections in about half the animals treated, while 7-NI completely abolished this effect. Interestingly 7-NI also abolished all the other symptoms of intoxication induced by Tx2-5, including salivation, respiratory distress and death. Tx2-5 killed all the animals of the control group and no one in the 7-NI-treated group. We conclude that (1) intraperitoneal injections of Tx2-5 induce a toxic syndrome that include penile erection, hypersalivation and death by respiratory distress or pulmonary edema; (2) pretreatment with the non-selective NOS inhibitor L-NAME reduces the penile erection and partially protects from the lethal effects of Tx2-5; (3) pretreatment with the nNOS-selective inhibitor 7-NI completely abolishes all the toxic effects of Tx2-5, including penile erection and death suggesting that nNOS is the major player in this intoxication; (4) toxins from other animals that affect sodium channels in the same way as Tx2-5 and induce similar toxic syndromes may have as a major common target, the activation of nitric oxide synthases.
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PMID:Blockade of neuronal nitric oxide synthase abolishes the toxic effects of Tx2-5, a lethal Phoneutria nigriventer spider toxin. 1524 65

Inducible nitric oxide synthase (iNOS) has been implicated in the pathophysiology of congestive heart failure (CHF). Given the extensive evidence supporting this concept, we hypothesized that iNOS deficiency (iNOS(-/-)) would attenuate the severity of CHF in mice. Mice were subjected to permanent occlusion [myocardial infarction (MI)] of the proximal left anterior descending coronary artery to produce CHF. Cardiac function was assessed in vivo using echocardiography and ultraminiature ventricular pressure catheters. Sham wild-type (n = 17), sham iNOS(-/-) (n = 8), MI wild-type (n = 56), and MI iNOS(-/-) (n = 48) mice were subjected to MI (or sham MI) and followed for 1 mo. Deficiency of iNOS did not alter survival during CHF compared with wild type (35% vs. 32%, P = not significant). Furthermore, fractional shortening and cardiac output were not significantly different between wild-type (9.6 +/- 2.0% and 441 +/- 20 microl.min(-1).g(-1)) and iNOS(-/-) (9.8 +/- 1.3% and 471 +/- 26 microl.min(-1).g(-1)) mice. The extent of cardiac hypertrophy and pulmonary edema was also similar between wild-type and iNOS(-/-) mice. None of the indexes demonstrated any significant differences between iNOS(-/-) and wild-type mice subjected to MI. These findings indicate that deficiency of iNOS does not significantly affect severe CHF in mice after MI.
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PMID:Deficiency of iNOS does not attenuate severe congestive heart failure in mice. 1531 10

The present study was undertaken to evaluate possible roles of L-glutamate ionotropic receptors in neurogenic pulmonary edema. Perfusion of L-glutamate into the fourth ventricles of rats increased nitric oxide (NO) signals in the efflux solution concentration-dependently, significantly reducing both the occurrence and severity of neurogenic pulmonary edema. This effect was completely reversed by prior intracisternal injection of an NO synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), or an N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine maleate (MK-801), and partially by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a 2-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA)/kainic acid receptor antagonist. Administration of MK-801 or CNQX alone, without L-glutamate, almost completely prevented neurogenic pulmonary edema development. These results suggest that endogenous L-glutamate may facilitate underlining disease process, whereas L-glutamate exogenously applied into the fourth ventricle may have an inhibitory action via release of NO, through ionotropic receptors.
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PMID:A role for L-glutamate ionotropic receptors in the development of rat neurogenic pulmonary edema. 1538 Oct 47


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