Assay of Pulmonary Microvascular Endothelial Angiotensin-Converting Enzyme in Vivo: Comparison of Three Probes

Orfanos, S. E.; Chen, X.L.; Ryan, James W.; Chung, Alfred; Burch, Sandra E.; Catravas, John D.

doi:10.1006/taap.1994.1013

Cited by 28 publications

(22 citation statements)

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“…17 However, BPAP binding by albumen does not necessarily predict similar binding by native serum proteins, and serum protein binding of BPAP does not appear to be a factor limiting BPAP hydrolysis in vivo. 18 The sample-to-sample variability in BPAP hydrolysis (Figure 1) reflects ACE activity within individual groups of capillaries and may be influenced by substrate transit time, enzyme concentration, and the enzyme kinetic constants, as in Equation 5. The pattern observed suggests the presence of mild heterogeneity in capillary transit times, since capillary enzyme concentrations and ACE catalytic properties should remain unchanged.…”

Section: Discussionmentioning

confidence: 99%

“…ACE function was assessed with indicator-dilution techniques and study of the transpulmonary utilization of the synthetic ACE substrate BPAP. PCEB-ACE dysfunction has been an early and sensitive finding in animal models of lung injury, 8,9 and, under physiological conditions, PCEB-ACE assays estimate enzyme mass 5 and perfused vascular surface area. 7,15 Although ACE is present on all endothelial cells, microvessels, principally capillaries, are responsible for the great majority of single-pass transpulmonary hydrolysis, 9 whereas the contribution of plasma ACE is minimal.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7] This assumption is based on Equation 7: when k cat and K m remain constant, changes in A max /K m reflect changes in E (ie, enzyme mass). For enzymes evenly distributed along the luminal endothelial surface, such as ACE, changes in E should reflect changes in DPCSA.…”

Section: Discussionmentioning

confidence: 99%

“…3 Pulmonary endothelial ACE activity may be assessed in vivo by monitoring the hydrolysis of a synthetic substrate in plasma during a single passage through the lungs. 5 Unlike natural angiotensin I and bradykinin, synthetic substrates of ACE do not alter vessel tone and are not metabolized by other endogenous peptidases and when hydrolyzed by ACE yield products that are easily separated from the parent compound by organic extraction. 6 The first and most widely used ACE substrate to date is the highly specific tripeptide benzoyl-Phe-Ala-Pro (BPAP).…”

mentioning

confidence: 99%

“…6 ACE molecules are uniformly distributed along the luminal pulmonary endothelial surface, including the membrane caveolae, 3 suggesting that in addition to its biological activity, pulmonary capillary endotheliumbound ACE (PCEB-ACE) may be a useful indicator of endothelial function and allow estimation of the perfused capillary surface area under physiological conditions. 2,5,7 Moreover, PCEB-ACE dysfunction is an early and sensitive index of lung vascular injury. 8,9 Thus monitoring of PCEB-ACE activity in humans might be used to estimate changes in perfused capillary surface area, to quantify the degree of endothelial dysfunction, and as a biochemical marker to identify early vascular lung injury.…”

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confidence: 99%

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

et al. 1999

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 1999

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Estimation of the dissociation constants for pulmonary endothelial angiotensin converting enzyme reactions with trandolaprilat and enalaprilat in vivo

et al. 1998

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Pulmonary capillary endothelial dysfunction in early systemic sclerosis

Orfanos

Psevdi

Stratigis

et al. 2001

Arthritis & Rheumatism

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Objective Pulmonary capillary endothelium–bound angiotensin‐converting enzyme (PCEB‐ACE) activity is a sensitive and quantifiable index of endothelial function in vivo. Systemic sclerosis (SSc) is characterized by endothelial damage and excess collagen formation, causing mainly pulmonary hypertension (PH) in the limited cutaneous SSc (lcSSc) subset and interstitial lung disease with pulmonary interstitial fibrosis (PIF) in the diffuse cutaneous SSc (dcSSc) subset. This study was undertaken to investigate the hypothesis that PCEB‐ACE activity is reduced early in SSc, in the absence of PH or PIF. Methods Applying indicator‐dilution techniques, we measured single‐pass transpulmonary hydrolysis and percent metabolism (%M) of a synthetic ACE substrate and calculated functional capillary surface area (FCSA) in 25 SSc patients and 11 controls. Substrate hydrolysis and %M reflect ACE activity per capillary; FCSA reflects ACE activity per vascular bed. Results PCEB‐ACE activity was decreased in both SSc subsets. Among patients without PH, substrate hydrolysis and %M were decreased in patients with lcSSc and more profoundly in those with dcSSc; loss of FCSA normalized to body surface area (FCSA/BSA) was observed in dcSSc, but not in lcSSc. High‐resolution computed tomography of the lung, performed in all SSc patients, revealed no correlation between substrate %M, hydrolysis, or FCSA/BSA and the degree of PIF; 5 dcSSc and 5 lcSSc patients with no detectable PIF exhibited decreases in hydrolysis and %M, while FCSA/BSA was decreased only in dcSSc. Conclusion Depression of PCEB‐ACE activity, indicating pulmonary endothelial dysfunction, occurs early in SSc, in the absence of PH or PIF, and is more pronounced, at this early pulmonary disease stage, in dcSSc than in lcSSc.

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Assay of Pulmonary Microvascular Endothelial Angiotensin-Converting Enzyme in Vivo: Comparison of Three Probes

Cited by 28 publications

References 0 publications

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

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

Estimation of the dissociation constants for pulmonary endothelial angiotensin converting enzyme reactions with trandolaprilat and enalaprilat in vivo

Pulmonary capillary endothelial dysfunction in early systemic sclerosis

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