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(Circulation. 1999;99:1593.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

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

Stylianos E. Orfanos, MD, PhD; David Langleben, MD; Joseph Khoury, MSc; Robert D. Schlesinger, MD; Leonidas Dragatakis, MD; Charis Roussos, MD, PhD; James W. Ryan, MD, DPhil; John D. Catravas, PhD

From the Division of Cardiology, Jewish General Hospital, McGill University, Montreal, Canada (S.E.O., D.L., J.K., R.D.S., L.D.); the Critical Care Department, Evangelismos Hospital, University of Athens Medical School, Athens, Greece (S.E.O., C.R.); and the Vascular Biology Center, Medical College of Georgia, Augusta (J.W.R., J.D.C.).

Correspondence to Dr David Langleben, Division of Cardiology, Jewish General Hospital, 3755, Chemin de la Cote Ste-Catherine, Room E-258, Montreal, P.Q. H3T 1E2, Canada. E-mail mddl{at}musica.mcgill.ca

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 ³H-benzoyl-Phe-Ala-Pro (³H-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.

Key Words: lung • endothelium • circulation • angiotensin • enzymes • hypertension, pulmonary

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