Impaired angiotensin conversion and bradykinin clearance in experimental canine pulmonary emphysema

ciated with abnormal blood pressure regulation. Be-cause the lung is the principal site of angiotensin con-version and because hypoxia decreases converting enzyme activity, we examined whether angiotensin con-verting enzyme activity was impaired in lung disease. 12 dogs received a 6 wk course of aerosolized and in-tratracheal papain that produced moderate panlobular emphysema. These dogs and 24 control dogs were anesthetized and sampling catheters were placed under fluoroscopic control. Angiotensin conversion was measured by a blood pressure response bioassay. Pulmonary converting enzyme activity was also as-sessed by infusing bradykinin (BK) and using radioim-munoassay to measure the instantaneous clearance of BK and the concentration of BK in the pulmonary artery which first produced spillover of BK into left atrial blood. Angiotensin conversion was reduced in the emphysematous dogs to 81.1 % (13.2 SD) from 92 % (6 SD) in the control dogs (P < 0.01). Instantaneous clear-ance of BK in the emphysematous dogs was only slightly reduced (93%), despite reduction in their Pao2 to 75 mm Hg, indicating that the greatest proportion of the perfused vascular bed was exposed to alveolar Po2 of>90mm Hg. However, the barrier to BK passage provided by the lung, and measured by the spillover level, was reduced Y4 to 2 that observed in control animals. That the defect was promptly corrected by supplemental oxygen indicates that regional pul-monary vascular converting enzyme activity had been impaired by regional alveolar hypoxia, which per-mitted some peptide to pass through the lung