Protein kinase C activation does not stimulate lung liquid clearance in anesthetized sheep

Although active transport of ions could play an important role in the resolution process of pulmonary edema, the exact mechanism regulating this process is still unknown. In this study, we investigated the effect of phorbol myristate acetate (PMA) on lung liquid clearance in anesthetized, ventilated sheep to evaluate the possible role of protein kinase C. To study lung liquid and protein clearance, we measured the removal of 100 ml of autologous serum from the air spaces of anesthetized sheep. Either serum alone or serum mixed with PMA (10(-7) M) was instilled. After 4 h, the residual lung water was 76.8 +/- 9.2 ml when serum alone was instilled and 79.5 +/- 15.7 when serum with PMA (10(-7) M) was instilled. The lack of effect of PMA (10(-7) M) on lung liquid clearance cannot be explained by increased movement of liquid from the vascular space to the air space since we did not have any evidence of increased pressure or increased permeability in the lung. This lack of effect of PMA (10(-7) M) is not due to an absence of stimulation of protein kinase C since instillation of BSA and PMA (10(-7) M) in rat lung produced a translocation of protein kinase C activity from the cytosolic fraction to the membrane fraction 2 h after the instillation. These results were confirmed in two sheep experiments, which demonstrated clear activation of protein kinase C after 4 h. These data suggest that activation of protein kinase C does not stimulate lung liquid clearance. However, a possible role of protein kinase C in modulating lung liquid clearance has not been excluded.