Scorpion venom decreases lung liquid clearance in rats.

It has been reported that scorpion venom causes respiratory failure and pulmonary edema. However, the effects of this toxin on lung edema clearance have not been previously studied. We examined the effects of scorpion (Tityus serrulatus) venom on the ability of the lung to clear fluid and on alveolar epithelial Na,K-ATPase. The wet-to-dry lung weight ratio was increased in anesthetized rats injected intraperitonally with scorpion venom. Lung edema clearance decreased by up to approximately 60% in rats injected with the venom. Na,K-ATPase alpha1- and beta1-subunit protein abundance and activity decreased at the basolateral membranes of alveolar epithelial type II cells incubated with scorpion venom as compared with that of control animals. There was no difference in cell injury in alveolar epithelial type II cells incubated with scorpion venom for 60 minutes compared with that of control animals. We provide here the first evidence that scorpion venom decreases lung liquid clearance, probably by downregulating Na,K-ATPase in the alveolar epithelium.

Na,K-ATPase overexpression improves alveolar fluid clearance in a rat model of elevated left atrial pressure.

BACKGROUND: Acute elevation of left atrial pressure (LAP) increases extravascular water and impairs active Na(+) transport in rat lungs. We have reported that overexpression of Na,K-ATPase subunit genes in the alveolar epithelium increases alveolar fluid clearance (AFC) in normal and injured rat lungs with normal LAP. We reasoned that adenovirus-mediated transfer of an Na,K-ATPase beta-subunit gene to the alveolar epithelium could improve AFC in rat lungs in the presence of acutely elevated LAP. METHODS AND RESULTS: Normal rats were infected with 4x10(9) plaque-forming units of E1a(-)/E3(-) recombinant adenoviruses that contained a cytomegalovirus promoter coupled to a rat Na,K-ATPase beta(1)-subunit cDNA (adbeta(1)) or no cDNA (adNull) 7 days before study. Na,K-ATPase alpha(1)- and beta(1)-subunit abundance in basolateral cell membranes isolated from the peripheral lung was significantly increased in adbeta(1)-infected lungs compared with sham and adNull-infected controls. In all groups, elevation of LAP reduced membrane-bound Na,K-ATPase abundance; however, abundance in adbeta(1)-infected lungs remained greater than in controls. AFC, measured with a fluid-filled isolated lung preparation in the presence of elevated LAP (15 cmH(2)O), in Na,K-ATPase beta(1)-subunit-overexpressing lungs was up to 100% greater than in controls and was not different from rats studied at normal LAP (0 cmH(2)O). CONCLUSIONS: These data suggest that alveolar overexpression of an Na,K-ATPase beta(1)-subunit can counteract downregulation of membrane-bound solute transporters owing to elevated pulmonary vascular pressures and can restore active Na(+) transport and AFC in this rat model of acute hydrostatic pulmonary edema.