Inhibition of endothelial‐bound angiotensin converting enzyme, <i>in vivo</i>

Catravas, John D.; Ryan, James W.; Chung, Alfred; Quinn, Nancy E.; Anthony, Betty L.

doi:10.1111/j.1476-5381.1990.tb12100.x

Cited by 7 publications

(8 citation statements)

References 22 publications

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“…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. ACE inhibitors inhibit endothelium-bound ACE, 16 and our subjects were carefully questioned about ACE inhibitor usage.…”

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%

“…Because of the minimal contribution of both the extracapillary endothelium-bound 9 and the plasma soluble ACE to substrate conversion, 9 the reaction time is in practical terms equal to t c (ie, capillary transit time 12 with the cis isomer being nonreactive, Equation 4 was further modified to the applied Equation 5 7,13 to incorporate the nonreactive fraction (nrfϭ7%) of BPAP 13 :…”

Section: Calculations Of Ace Activity Parametersmentioning

confidence: 99%

“…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: Calculations Of Ace Activity Parametersmentioning

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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“…Using indicatordilution-type techniques under first-order reaction conditions, we estimated the %M and the hydrolysis of BPAP and calculated the kinetic parameters of this reaction. This method provides estimates of pulmonary endothelial ACE activity in the microvessels, which is almost exclusively capillary-based (i.e., PCEB-ACE activity) (8,16,17). One milliliter of a 3 H-BPAP solution (30 Ci/1.2 ml of 0.9% saline, or 22.2 Ci/mmole) was used for each injection, followed by 5 ml of 0.9% saline flush.…”

Section: Methodsmentioning

confidence: 99%

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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Inhibition of pulmonary endothelial angiotensin converting enzyme activity by trandolaprilat in vivo

et al. 1997

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Inhibition of endothelial‐bound angiotensin converting enzyme, in vivo

Cited by 7 publications

References 22 publications

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

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

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

Inhibition of pulmonary endothelial angiotensin converting enzyme activity by trandolaprilat in vivo

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