Research and development of therapy for lung injury by activation of alveolar fluid and protein reabsorption mechanism

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The prognosis of acute lung injury is poor and a mew therapy is necessary to improve the outcome. Recently, alveolar fluid clearance has been considered to play an important role in the resolution of acute lung injury. To increase alveolar fluid clearance, an administration of a beta adrenergic agonist is a candidate, but the mechanism responsible for the beta agonist mediated alveolar fluid clearance is still uncertain. We studied mechanisms responsible for alveolar fluid and protein clearance in rots and excised human lungs and developed a therapy for lung injury. First, we found that CFTR plays a role in b_1-adrenergic agonist-stimulated alveolar fluid clearance in rat lungs. Second, endogenous catecholamine concentrations in pulmonary edema fluid are probably not sufficient to stimulate alveolar fluid clearance. In contrast, administration of exogenous catecholamines into the distal airspaces can stimulate alveolar fluid clearance in the human lung, an effect that is mediated in part by CH R. Therefore, exogenous cAMP-dependent stimulation will probably be required to accelerate the resolution of alveolar edema in the lungs of patients with pulmonary edema. Third, chronic pulmonary artery occlusion increases alveolar fluid clearance via a_1-Na, K-ATPase overexpression in rats. Fourth, endogenous catecholamine stimulated a-adrenoceptors and increased alveolar fluid clearance in rats with acute pancreatitis. Finally, basal alveolar fluid clearance in obese Zucker rat is mediated the increased function of b_2-adrenoceptor. The current study indicates that endogenous and exogenous catecholamines play an important role in the improvement of acute lung injury.