Pulmonary angiotensin-converting enzyme substrate hydrolysis during exercise

Dupuis, Jocelyn; Goresky, Carl A.; Ryan, Joanne; Rouleau, J L; Bach, Glen G.

doi:10.1152/jappl.1992.72.5.1868

Cited by 27 publications

(12 citation statements)

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“…The line for the control group was quite close to the line of identity. This line is similar to those generated in animal models (22,27) and is likely representative of the true surface area-flow relationship in healthy human subjects under physiologic resting conditions. The line for the IPAH group was nearly parallel to the line for the controls, suggesting that although the lungs of patients with IPAH are operating with a reduced number of perfused functional capillaries, this number would be close to the number of capillaries that would be perfused in a healthy lung under low flow states.…”

Section: Discussionsupporting

confidence: 77%

Pulmonary capillary endothelial metabolic dysfunction: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension

Langleben¹,

Orfanos²,

Giovinazzo³

et al. 2008

Arthritis & Rheumatism

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Objective. Pulmonary endothelial dysfunction is intertwined with the development and progression of pulmonary arterial hypertension (PAH). Pulmonary endothelium is an active metabolic tissue in healthy human subjects. This study was undertaken to determine the effects of PAH on pulmonary endothelial angiotensin-converting enzyme (ACE) activity and to identify differences between common PAH types, i.e., PAH related to connective tissue disease (PAH-CTD) versus idiopathic PAH (IPAH).Methods. Nineteen patients with PAH-CTD, 25 patients with IPAH, and 23 control subjects were evaluated. The single-pass transpulmonary percent metabolism (%M) and hydrolysis (both reflecting enzyme activity per capillary) of an ACE synthetic substrate were determined. In addition, the calculated functional capillary surface area (FCSA), normalized to body surface area (BSA), was determined.Results. The %M values in patients with PAH-CTD (mean ؎ SEM 53.6 ؎ 3.6%) were significantly reduced compared with those in control subjects (P < 0.01) and those in patients with IPAH (P < 0.03), but were similar between the IPAH and control groups (mean ؎ SEM 66.2 ؎ 3.6% and 74.7 ؎ 2.7%, respectively). Substrate hydrolysis was also significantly reduced in patients with PAH-CTD. The FCSA/BSA was significantly reduced in patients with PAH-CTD (mean ؎ SEM 1,068 ؎ 118 ml/minute/m 2 ) and in patients with IPAH (1,443 ؎ 186 ml/minute/m 2 ) compared with that in controls (2,948 ؎ 245 ml/minute/m 2 ; P < 0.01 for both). At a given cardiac index, the FCSA/BSA tended to be lower in the PAH-CTD group than in the IPAH group. Moreover, unlike in IPAH, a linear relationship between the FCSA/BSA and the diffusing capacity for carbon monoxide (DLCO) was observed in PAH-CTD (r ‫؍‬ 0.54, P < 0.03).Conclusion. The metabolically functional pulmonary capillary bed appears to be reduced to an equal extent in PAH-CTD and IPAH. However, %M and hydrolysis appear to be reduced in PAH-CTD but not in IPAH, reflecting relatively diminished ACE activity on the pulmonary capillary endothelial cells of patients with PAH-CTD, and showing that pulmonary endothelial metabolic function differs between PAH types. This study also provides the first functional evidence that a

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Section: Discussionsupporting

confidence: 77%

Pulmonary capillary endothelial metabolic dysfunction: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension

Langleben¹,

Orfanos²,

Giovinazzo³

et al. 2008

Arthritis & Rheumatism

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“…24 It has been suggested that A max /K m cannot be used as a quantitative index of perfused capillary surface area because of the presence of the nonreactive cis isomer BPAP fraction. 15,25 This fraction was estimated to be Ϸ15% in buffer solution, 26 whereas in vivo it appears to represent 7% of all BPAP, 13 probably because of the presence of natural isomerases in plasma. However, studies done with different substrates concurrently injected, or correcting for the nonreactive fraction, confirm that A max /K m is a quantifiable index of perfused lung capillaries.…”

Section: Discussionmentioning

confidence: 99%

“…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. 9 Thus in our studies, measurement of pulmonary ACE activity represents in practical terms PCEB-ACE activity.…”

Section: Discussionmentioning

confidence: 99%

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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“…Now assume that the tracer oxygen undergoes instantaneous equilibrium partition between RBCs, plasma, Disse space and hepatocytes at each point along the length (that is, y = h p ; u = u; and z = Ahpu; where Ac, is the ratio of erythrocyte/plasma oxygen concentration and hh is the ratio of hepatocyte/plasma oxygen concentrafion, as indicated by our qualitative analysis of the data. The solution to equation 5 for an impulse input is, as described previously (5, 8, 16), where qo is the amount of tracer injected, Fb is sinusoidal blood flow, kses is the form of the rate constant which appears in the integrated equation, (20). Equation 6 can be viewed as an analog of the Crone expression (211, in which sequestration takes the place of the permeability surface area product.…”

Section: It Can Be Shownmentioning

confidence: 99%

Flow–Limited Tracer Oxygen Distribution in the Isolated Perfused Rat Liver: Effects of Temperature and Hematocrit

et al. 1992

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We used the multiple-indicator dilution technique to examine the kinetics of tracer oxygen distribution and uptake in the rat liver perfused in a nonrecirculating fashion with blood. 51Cr-labeled 18O2-saturated erythrocytes, labeled albumin, sucrose and water (the tracers for oxygen and vascular, interstitial and cellular references) were injected simultaneously into the portal vein. Timed anaerobic samples were collected from the hepatic vein and analyzed by mass spectrometry for relative 18O2 enrichment and radioactivity. In a set of experiments performed at 32 degrees C, oxygen uptake was substantially diminished; tracer oxygen profiles approached those expected for a completely recovered, flow-limited substance. At 37 degrees C, much larger tracer oxygen sequestration occurred. Experiments were carried out at each temperature at higher and lower hematocrit, and oxygen consumption at each temperature was found to be independent of hematocrit. The tissue space of distribution for tracer oxygen relative to the total sinusoidal vascular content was influenced by the hematocrit: it was smaller at higher hematocrit and larger at lower hematocrit, as expected. The derived partition coefficient of oxygen for liver cells relative to plasma (expressed in terms of the liver and plasma water spaces) was, on average, 2.62 ml/ml; it was independent of the hematocrit. Analysis of the indicator dilution experiments indicates that the tracer oxygen is distributed into tissue in a flow-limited rather than a barrier-limited fashion, and that with this, an ongoing concomitant intracellular sequestration of tracer can be seen.

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Pulmonary angiotensin-converting enzyme substrate hydrolysis during exercise

Cited by 27 publications

References 0 publications

Pulmonary capillary endothelial metabolic dysfunction: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension

Pulmonary capillary endothelial metabolic dysfunction: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension

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

Flow–Limited Tracer Oxygen Distribution in the Isolated Perfused Rat Liver: Effects of Temperature and Hematocrit

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