No abstract

Goat antibodies to pig lung angiotensin-converting enzyme (kininase II) were conjugated to microperoxidase. Rat lung tissue, previously incubated with non-immune goat serum, was incubated with the antibody-microperoxidase conjugate and then with H2O2 and 3,3-diaminobenzidine. Electron microscopy revealed reaction product on the plasma membrane and caveolae of endothelial cells, especially those of capillaries and venules. These results support the hypothesis that angiotensin I and bradykinin are metabolized by enzymes on the luminal surface of pulmonary endothelial cells.

Background-Pulmonary endothelium has metabolic functions including the conversion of angiotensin I to angiotensin II by angiotensin-converting ectoenzyme (ACE). In this study, we have validated an indicator-dilution technique that provides estimations of dynamically perfused capillary surface area (DPCSA) in humans, and we have characterized pulmonary endothelial ACE in vivo. Methods and Results-In 12 adults, single-pass transpulmonary (one or both lungs) hydrolysis of the specific ACE substrate 3 H-benzoyl-Phe-Ala-Pro ( 3 H-BPAP) was measured and expressed as % metabolism (%M) and vϭϪln(1ϪM). We also calculated A max /K m , an index of DPCSA. %M (70.1Ϯ3.2 vs 67.9Ϯ3.1) and v (1.29Ϯ0.14 vs 1.20Ϯ0.12) were similar in both lungs and the right lung, respectively, whereas A max /K m/ /body surface area decreased from 2460Ϯ193 to 1318Ϯ115 mL/min per square meter. Conclusions-Pulmonary endothelial ACE activity can be assessed in humans at the bedside by means of indicatordilution techniques. Our data suggest homogeneous pulmonary capillary ACE concentrations and capillary transit times (t c ) in both human lungs, and similar t c within the normal range of cardiac index. A max /K m in the right lung is 54% of total A max /K m in both lungs, suggesting that A max /K m is a reliable and quantifiable index of DPCSA in humans.