Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kidney plays a dominant role in maintaining sodium homeostasis. Despite wide variation in environmental exposure, the osmolality of the extracellular fluid that is determined by the sodium ion concentration is maintained within narrow margins. Derangement in function of proteins that transport Na+ and of those regulating the activity of these sodium-transporting proteins are likely to be responsible for a number of clinical disorders of fluid and electrolyte homeostasis. The amiloride-sensitive epithelial sodium channel (ENaC) is implicated in the control of blood pressure as demonstrated by the analysis of two genetic diseases, Liddle's syndrome and pseudohypoaldosteronism (PHA-1). Mutations have been identified in the genes coding for the alpha-, beta- or gamma-subunit of ENaC. ENaC constitutes the limiting step for sodium reabsorption in epithelial cells that line the distal nephron, distal colon, ducts of several exocrine glands and lung airways and might play an important role in pathophysiological and clinical conditions such as hypertension or lung edema.
 ...
PMID:Reversal of convention: from man to experimental animal in elucidating the function of the renal amiloride-sensitive sodium channel. 969 87

Case reports of neurogenic pulmonary edema (NPE) often indicate that the edema resolves quickly. Because plasma epinephrine concentration may be elevated in NPE, and epinephrine has been shown to increase the rate of alveolar liquid clearance (ALC), we determined if ALC was increased in a canine model of NPE produced by the intracisternal administration of veratrine. ALC was determined by instilling autologous plasma into a lower lung lobe and using the increase in instillate protein concentration after 4 h to calculate the volume of fluid cleared from the airspaces by mass balance. To prevent pulmonary hypertension and edema, which would confound the mass balance analysis, carotid arterial blood was allowed to drain into a reservoir as pulmonary arterial pressure started to rise after veratrine administration. ALC in animals administered veratrine (n = 6) was 30.4 +/- 1.6 (SE)% of the instilled volume compared with 14.1 +/- 2.1% observed in control animals. The increase in ALC could be inhibited by adrenalectomy, beta2-adrenergic blockade using ICI 118,551, or sodium channel blockade using amiloride and could be duplicated by infusing epinephrine to increase plasma epinephrine concentration to levels observed in NPE. These data indicate that the increased ALC was mediated by adrenal epinephrine and suggest that edema resolution in patients with NPE might be accelerated by endogenous epinephrine.
 ...
PMID:Adrenal epinephrine increases alveolar liquid clearance in a canine model of neurogenic pulmonary edema. 973 Oct 2

High-altitude pulmonary edema (HAPE) is a form of lung edema which occurs in otherwise healthy subjects, thereby allowing the study of underlying mechanisms of pulmonary edema in the absence of confounding factors. Exaggerated pulmonary hypertension is a hallmark of HAPE and is thought to play an important part in its pathogenesis. Pulmonary vascular endothelial dysfunction and augmented hypoxia-induced sympathetic activation may be underlying mechanisms contributing to exaggerated pulmonary vasoconstriction in HAPE. Recent observations by our group suggest, however, that pulmonary hypertension itself may not be sufficient to trigger HAPE. Based on studies in rats, indicating that perinatal exposure to hypoxia predisposes to exaggerated hypoxic pulmonary vasoconstriction in adulthood, we examined effects of high-altitude exposure on pulmonary-artery pressure in a group of young adults who had suffered from transient perinatal pulmonary hypertension. We found that these young adults had exaggerated pulmonary vasoconstriction of similar magnitude to that observed in HAPE-susceptible subjects. Surprisingly, however, none of the subjects developed lung edema. These findings strongly suggest that additional mechanisms are needed to trigger pulmonary edema at high-altitude. Observations in vitro, and in vivo suggest that a defect of the alveolar transepithelial sodium transport could act as a sensitizer to pulmonary edema. The aim of this article is to review very recent experimental evidence consistent with this concept. We will discuss data gathered in mice with targeted disruption of the gene of the alpha subunit of the amiloride-sensitive epithelial sodium channel (alpha ENaC), and present preliminary data on measurements of transepithelial sodium transport in vivo in HAPE-susceptible and HAPE-resistant mountaineers.
 ...
PMID:High-altitude pulmonary edema: from exaggerated pulmonary hypertension to a defect in transepithelial sodium transport. 1063 96

Many toxins from scorpion venoms activate sodium channels, thereby enhancing neurotransmitter release. The aim of the present work was to determine if the in vivo and in vitro effects of Leiurus quinquestriatus venom (LQQ) could be ameliorated by lignocaine, a sodium channel blocker. In urethane anaesthetised rabbits, LQQ venom (0.5 mg kg(-1), i.v.) caused initial hypotension and bradycardia followed by hypertension, pulmonary oedema, electrocardiographic changes indicating conduction defects, ischaemia, infarction, and then hypotension and death. Lignocaine (1 mg kg(-1) i.v. bolus initially, followed by i.v. infusion of 50 microg kg(-1) min(-1)) significantly attenuated the majority of the venom-evoked effects and reduced mortality. Addition of LQQ venom (1, 3 and 10 microg ml(-1)) to chick biventer cervicis, guinea pig ileum, and rat vas deferens preparations, increased the height of electrically-induced twitches, elevated resting tension, and caused autorhythmic oscillations. Lignocaine (3 x 10(-4)-1.2 x 10(-3) M) greatly attenuated these venom-evoked actions in the three preparations. Antagonists of appropriate neurotransmitters were also tested to determine the contribution of released transmitters to LQQ effects. Atropine significantly decreased the venom-elicited effects on guinea pig ileum preparations, while prazosin and guanethidine significantly reduced the venom's actions on rat vas deferens. In chick biventer cervicis preparations, tubocurarine and hexamethonium significantly attenuated the venom-induced effects. This study supports the hypothesis that many effects of LQQ venom involve the release of neurotransmitters and may be ameliorated by treatment with lignocaine.
 ...
PMID:The effects of lignocaine on actions of the venom from the yellow scorpion "Leiurus quinquestriatus" in vivo and in vitro. 1085 17

Central nervous system and cardiovascular toxicity are well-known side effects of bupivacaine. We report a case of bupivacaine-induced myocardial depression and cardiogenic pulmonary edema. A previously healthy woman developed soon after bupivacaine epidural injection of 5 mL 0.5% (25 mg) cardiogenic shock complicated with pulmonary edema. There were pronounced rales on auscultation with a butterfly sign on chest radiograph. A cardiac ultrasound showed reduced myocardial contractility, diffuse hypokinesia, left ventricular ejection fraction (LVEF) 25%, mitral and pulmonary insufficiency. Right heart catheterization showed increased pulmonary artery wedge pressure (34 mm Hg) and a pulmonary artery pressure of 48 over 33 mm Hg. These findings suggest myocardial depression owing to bupivacaine sodium channel blocking of myocardial nerve and tissue and subsequent reduction of myocardial contractility. The patient completely recovered with normalization of clinical, roentenographic, ultrasound, and hemodynamic findings and discharged 10 days later in good condition.
 ...
PMID:Bupivacaine-induced myocardial depression and pulmonary edema: a case report. 1095 83

The epithelial sodium channel (ENaC) plays a key role in the regulation of fluid absorption in the kidney, lung, colon and exocrine glands, and in the regulation of blood pressure. Abnormal functioning of ENaC is associated with several human diseases, including pseudohypoaldosteronism type I, Liddle's syndrome, pulmonary edema, and cystic fibrosis. ENaC is regulated by several hormones, ions and accessory proteins. This review focuses on the regulation of ENaC by recently described accessory proteins, mainly Nedd4, syntaxin 1A, CFTR, sgk, K-Ras2A and Cap-1.
 ...
PMID:Regulation of the epithelial sodium channel (ENaC) by accessory proteins. 1099 Mar 73

The epithelial sodium channel (ENaC) in the apical membrane of polarized epithelial cells is the rate-limiting step for Na entry into the cell; in series with the basolateral Na pump, it allows the vectorial transepithelial transport of Na ions. ENaC is expressed in different epithelia like the distal nephron or colon, and the airways epithelium. In the lung ENaC controls the composition and the amount of pulmonary fluid, whereas in the distal nephron ENaC under the control of aldosterone and vasopressin, is essential to adapt the amount of Na+ reabsorbed with the daily sodium intake. Activating mutations of ENaC cause severe disturbances of Na+ homeostasis leading to hypertension in human and in mouse models. Functional expression of ENaC in different cell systems allowed the identification of structural domains of the protein that are essential for channel function and/or modulation of channel activity. Site-directed mutations in specific domains of the channel protein lead to channel hyperactivity or channel loss of function. Knowledge about ENaC structure-function relationships opens new opportunities for development of pharmacological tools for controlling ENaC activity, such as channel activators of potential benefit in the treatment of pulmonary edema, or highly potent ENaC blockers with natriuretic effects.
 ...
PMID:Structure function relationships of ENaC and its role in sodium handling. 1195 Jan 46

The discovery of mechanisms that regulate salt and water transport by the alveolar and distal airway epithelium of the lung has generated new insights into the regulation of lung fluid balance under both normal and pathological conditions. There is convincing evidence that active sodium and chloride transporters are expressed in the distal lung epithelium and are responsible for the ability of the lung to remove alveolar fluid at the time of birth as well as in the mature lung when pathological conditions lead to the development of pulmonary edema. Currently, the best described molecular transporters are the epithelial sodium channel, the cystic fibrosis transmembrane conductance regulator, Na+-K+-ATPase, and several aquaporin water channels. Both catecholamine-dependent and -independent mechanisms can upregulate isosmolar fluid transport across the distal lung epithelium. Experimental and clinical studies have made it possible to examine the role of these transporters in the resolution of pulmonary edema.
 ...
PMID:Lung epithelial fluid transport and the resolution of pulmonary edema. 1208 29

Alveolar hypoxia may impair sodium-dependent alveolar fluid transport and induce pulmonary edema in rat and human lung, an effect that can be prevented by the inhalation of beta(2)-agonists. To investigate the mechanism of beta(2)-agonist-mediated stimulation of sodium transport under conditions of moderate hypoxia, we examined the effect of terbutaline on epithelial sodium channel (ENaC) expression and activity in cultured rat alveolar epithelial type II cells exposed to 3% O(2) for 24 h. Hypoxia reduced transepithelial sodium current and amiloride-sensitive sodium channel activity without decreasing ENaC subunit mRNA or protein levels. The functional decrease was associated with reduced abundance of ENaC subunits (especially beta and gamma) in the apical membrane of hypoxic cells, as quantified by biotinylation. cAMP stimulation with terbutaline reversed the hypoxia-induced decrease in transepithelial sodium transport by stimulating sodium channel activity and markedly increased the abundance of beta-and gamma-ENaC in the plasma membrane of hypoxic cells. The effect of terbutaline was prevented by brefeldin A, a blocker of anterograde transport. These novel results establish that hypoxia-induced inhibition of amiloride-sensitive sodium channel activity is mediated by decreased apical expression of ENaC subunits and that beta(2)-agonists reverse this effect by enhancing the insertion of ENaC subunits into the membrane of hypoxic alveolar epithelial cells.
 ...
PMID:Hypoxia and beta 2-agonists regulate cell surface expression of the epithelial sodium channel in native alveolar epithelial cells. 1237 21

To determine if pulmonary oedema fluid (EF) alters ion and fluid transport of distal lung epithelium (DLE), EF was collected from rats in acute heart failure. EF, but not plasma, increased amiloride-insensitive short circuit current (I(sc)) and Na(+)-K(+) ATPase protein content and pump activity of DLE grown in primary culture. Inhibitors of Cl(-) transport or cGMP-gated cation channels had a significant (P < 0.05), but limited ability to block the increased I(sc). EF increased amiloride-insensitive, but not amiloride-sensitive, DLE apical membrane Na(+) conductance. The level of mRNA encoding epithelial sodium channel (ENaC) subunits was unchanged (alpha, beta), or decreased (gamma, P < 0.05) in EF-exposed DLE. EF also induced an amiloride-insensitive increase in the potential difference across murine tracheal cysts. Distal lung explants from late gestation wild-type and alpha-ENaC-deficient fetal mice, which normally expand due to liquid secretion, decreased in size due to liquid absorption when exposed to EF. Trypsin digestion or heat treatment of EF abrogated the ability of EF to increase amiloride-insensitive I(sc) in DLE and liquid absorption by distal lung explants. Thus proteins or protein-dependent factors within cardiogenic EF induce an alpha-ENaC-independent and amiloride-insensitive apical membrane Na(+) conductance and liquid absorption in the distal lung.
 ...
PMID:Pulmonary oedema fluid induces non-alpha-ENaC-dependent Na(+) transport and fluid absorption in the distal lung. 1238 7


1 2 3 4 5 6 7 Next >>