Treatment of Pulmonary Edema by ENaC Activators/Stimulators

摘要: Lungs contain a particular amount of fluid that is crucial for proper lung function. This content tightly controlled within certain limits. Fluid accumulation in the alveolar airspace impairs gas exchange and represents lifethreatening condition referred to as pulmonary edema. Ion transport processes by epithelia represent mechanism, responsible absorption from airspace. Thus, it obvious consider ion target therapeutic interventions The principle mechanism is: Na(+) diffuses through luminal channels into epithelial cells extruded Na(+)/K(+)-ATPases at basolateral side. process generates an osmotic gradient driving force absorption. rate limited number/activity Na+ membrane cells. Although different have been identified, channel (ENaC) major player participates Na(+)-driven thus suitable treatment article reviews cellular mechanisms which ENaC activity can be increased (lectins, proteases, β-adrenoceptors, mineralo-/glucocorticoid-receptors). These are involved regulating ENaC-dependent under physiological conditions. Additionally, pre-clinical well some preliminary clinical studies revealed "ENaC-activators/stimulators" (β2-adrenoceptor agonists mineralo-/glucocorticoid-receptor agonists) could beneficial patients with However, outcome subsequently performed multicenter trials edema was disappointing.