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 3H-benzoyl-Phe-Ala-Pro (3H-BPAP) was measured and expressed as % metabolism (%M) and v=-ln(1-M). We also calculated Amax/Km, 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 Amax/Km//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 (tc) in both human lungs, and similar tc within the normal range of cardiac index. Amax/Km in the right lung is 54% of total Amax/Km in both lungs, suggesting that Amax/Km is a reliable and quantifiable index of DPCSA in humans.