Exogenous bradykinin is known to be a pulmonary vasodilator under hypoxic conditions. Bradykinin is released from the lungs of neonatal animals on ventilation with air or oxygen. The pulmonary vascular endothelium is the major site of bradykinin inactivation in the body. Inhibition of the inactivating enzyme prevents the development of pulmonary hypertension in chronic animal models of hypoxic pulmonary hypertension. Our experiments are designed to determine whether there is a correlation between changes in pulmonary vascular reactivity in the anesthetised dog at different oxygen tensions and alterations in the measured levels of bradykinin in the plasma. The hemodynamics and bradykinin levels are also being studied in dogs given low dose endotoxin, or kininase I and II inhibitors. These inhibitors are also being tested in the isolated perfused rat lung. We have demonstrated a high fetal mortality in pregnant rabbits treated with the kininase II inhibitor, captopril. Further studies are being undertaken to measure changes in uteroplacental blood flow in these rabbits.