Abstract
Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal ectoenzyme. The majority of ACE has been found on the pulmonary capillary endothelium (PCE). Pulmonary capillary endothelium-bound (PCEB)-ACE has been extensively studied by means of indicator dilution techniques in animals and man. We have recently developed and applied methodologies for assaying pulmonary capillary endothelium-bound (PCEB) angiotensin converting enzyme (ACE) activity in man. This article provides a summary of our studies in human subjects utilizing similar methodology. Trace amounts of the specific ACE substrate, (3)H-benzoyl-Phe-Ala-Pro ((3)H-BPAP; 40 microCi or 2 nmol), was injected as a bolus into the subclavian vein of patients and immediately blood was withdrawn from a radial arterial catheter. Plasma concentrations of surviving substrate and product ((3)H-benzoyl-Phe) were estimated and BPAP utilization was calculated during a single transpulmonary passage. To investigate the PCE in this manner we tested the hypothesis that PCEB-ACE is depressed in patients diagnosed with acute lung injury and estimated interaction of an ACE inhibitor (enalaprilat) with PCE in human subjects. An inverse correlation was found between the pulmonary endothelium-bound ACE activity (v) and the lung injury score (r=0.379; p<0.01). Similarly, an inverse correlation was found between the pulmonary capillary perfusion index (CPI) and the lung injury score (r=0.284, p<0.05). PCEB-ACE activity in the group of patients with mild lung injury was significantly different from the group of control patients (0.44 +/- 0.048 vs. 1.15 +/- 0.05; p<0.01). Trace amounts (1.5 microg/kg) of enalaprilat had no significant effect on mean arterial pressure (91 +/- 6 vs. 84 +/- 7 vs. 88 +/- 6 mmHg for T(1), T(2) and T(3), respectively), but significantly decreased PCEB-ACE activities. When normalized to pre-drug (T(1)) activity levels, enalaprilat inhibited PCEB and SE ACE activity at T(2) by 74 +/- 6 and 68 +/- 6%, respectively. PCEB-ACE measurements can be used in clinical practice for estimating PCE functions and can provide new insight into the physiology of the pulmonary circulation.
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