Pulmonary Capillary Endothelium-Bound Angiotensin-Converting Enzyme Activity in Humans

Abstract

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 v=−ln(1−M). We also calculated A max /K m , an index of DPCSA. %M (70.1±3.2 vs 67.9±3.1) and v (1.29±0.14 vs 1.20±0.12) were similar in both lungs and the right lung, respectively, whereas A max /K m/ /body surface area decreased from 2460±193 to 1318±115 mL/min per square meter. Conclusions —Pulmonary endothelial ACE activity can be assessed in humans at the bedside by means of indicator-dilution 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.