Assay of Pulmonary Microvascular Endothelial Angiotensin Converting Enzyme, in Vivo: Comparison of Three Methods

1993 ◽  
pp. 192-193
Author(s):  
S. E. Orfanos ◽  
X-L Chen ◽  
J. W. Ryan ◽  
A. Y. K. Chung ◽  
S. E. Burch ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Microvascular Endothelial

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

1994 ◽  
Vol 124 (1) ◽  
pp. 99-111 ◽  
Author(s):  
S.E. Orfanos ◽  
X.L. Chen ◽  
J.W. Ryan ◽  
A.Y.K. Chung ◽  
S.E. Burch ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Microvascular Endothelial

Immunotargeting of catalase to lung endothelium via anti-angiotensin-converting enzyme antibodies attenuates ischemia-reperfusion injury of the lung in vivo

2007 ◽  
Vol 293 (1) ◽  
pp. L162-L169 ◽  
Author(s):  
Kai Nowak ◽  
Sandra Weih ◽  
Roman Metzger ◽  
Ronald F. Albrecht ◽  
Stefan Post ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Dry Weight ◽  
Serum Levels ◽  
Converting Enzyme ◽  
Pulmonary Endothelium ◽  
Preferential Expression

Limitation of reactive oxygen species-mediated ischemia-reperfusion (I/R) injury of the lung by vascular immunotargeting of antioxidative enzymes has the potential to become a promising modality for extension of the viability of banked transplantation tissue. The preferential expression of angiotensin-converting enzyme (ACE) in pulmonary capillaries makes it an ideal target for therapy directed toward the pulmonary endothelium. Conjugates of ACE monoclonal antibody (MAb) 9B9 with catalase (9B9-CAT) have been evaluated in vivo for limitation of lung I/R injury in rats. Ischemia of the right lung was induced for 60 min followed by 120 min of reperfusion. Sham-operated animals (sham, n = 6) were compared with ischemia-reperfused untreated animals (I/R, n = 6), I/R animals treated with biotinylated catalase (CAT, n = 6), and I/R rats treated with the conjugates (9B9-CAT, n = 6). The 9B9-CAT accumulation in the pulmonary endothelium of injured lungs was elucidated immunohistochemically. Arterial oxygenation during reperfusion was significantly higher in 9B9-CAT (221 ± 36 mmHg) and sham (215 ± 16 mmHg; P < 0.001 for both) compared with I/R (110 ± 10 mmHg) and CAT (114 ± 30 mmHg). Wet-dry weight ratio of I/R (6.78 ± 0.94%) and CAT (6.54 ± 0.87%) was significantly higher than of sham (4.85 ± 0.29%; P < 0.05), which did not differ from 9B9-CAT (5.58 ± 0.80%). The significantly lower degree of lung injury in 9B9-CAT-treated animals compared with I/R rats was also shown by decreased serum levels of endothelin-1 (sham, 18 ± 9 fmol/mg; I/R, 42 ± 12 fmol/mg; CAT, 36 ± 11 fmol/mg; 9B9-CAT, 26 ± 9 fmol/mg; P < 0.01) and mRNA for inducible nitric oxide synthase (iNOS) [iNOS-GAPDH ratio: sham, 0.15 ± 0.06 arbitrary units (a.u.); I/R, 0.33 ± 0.08 a.u.; CAT, 0.26 ± 0.05 a.u.; 9B9-CAT, 0.14 ± 0.04 a.u.; P < 0.001]. These results validate immunotargeting by anti-ACE conjugates as a prospective and specific strategy to augment antioxidative defenses of the pulmonary endothelium in vivo.

Dual inhibition of angiotensin converting enzyme and neutral endopeptidase by omapatrilat in rat in vivo

2001 ◽  
Vol 44 (5) ◽  
pp. 411-418 ◽  
Author(s):  
Tom Bäcklund ◽  
Eeva Palojoki ◽  
Tina Grönholm ◽  
Anders Eriksson ◽  
Olli Vuolteenaho ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Neutral Endopeptidase ◽  
Converting Enzyme ◽  
Dual Inhibition

scholarly journals Novel activity of angiotensin-converting enzyme. Hydrolysis of cholecystokinin and gastrin analogues with release of the amidated C-terminal dipeptide

1989 ◽  
Vol 262 (1) ◽  
pp. 125-130 ◽  
Author(s):  
P Dubreuil ◽  
P Fulcrand ◽  
M Rodriguez ◽  
H Fulcrand ◽  
J Laur ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Chloride Ion ◽  
Peptide Bond ◽  
Major Product ◽  
Enzyme Hydrolysis ◽  
Ion Concentration ◽  
Converting Enzyme ◽  
Rabbit Lung ◽  
Hydrolysis Of

ACE (angiotensin-converting enzyme; peptidyl dipeptidase A; EC 3.4.15.1), cleaves C-terminal dipeptides from active peptides containing a free C-terminus. We investigated the hydrolysis of cholecystokinin-8 [CCK-8; Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] and of various gastrin analogues by purified rabbit lung ACE. Although these peptides are amidated at their C-terminal end, they were metabolized by ACE to several peptide fragments. These fragments were analysed by h.p.l.c., isolated and identified by comparison with synthetic fragments, and by amino acid analysis. The initial and major site of hydrolysis was the penultimate peptide bond, which generated a major product, the C-terminal amidated dipeptide Asp-Phe-NH2. As a secondary cleavage, ACE subsequently released di- or tri-peptides from the C-terminal end of the remaining N-terminal fragments. The cleavage of CCK-8 and gastrin analogues was inhibited by ACE inhibitors (Captopril and EDTA), but not by other enzyme inhibitors (phosphoramidon, thiorphan, bestatin etc.). Hydrolysis of [Leu15]gastrin-(14-17)-peptide [Boc (t-butoxycarbonyl)-Trp-Leu-Asp-Phe-NH2] in the presence of ACE was found to be dependent on the chloride-ion concentration. Km values for the hydrolysis of CCK-8, [Leu15]gastrin-(11-17)-peptide and Boc-[Leu15]gastrin-(14-17)-peptide at an NaCl concentration of 300 mM were respectively 115, 420 and 3280 microM, and the catalytic constants were about 33, 115 and 885 min-1. The kcat/Km for the reactions at 37 degrees C was approx. 0.28 microM-1.min-1, which is approx. 35 times less than that reported for the cleavage of angiotensin I. These results suggest that ACE might be involved in the metabolism in vivo of CCK and gastrin short fragments.

Interaction of mAb to angiotensin-converting enzyme (ACE) with antigen in vitro and in vivo: antibody targeting to the lung induces ACE antigenic modulation

1994 ◽  
Vol 6 (8) ◽  
pp. 1153-1160 ◽  
Author(s):  
Sergei Danilov ◽  
Elena Atochina ◽  
Holger Hiemisch ◽  
Tatiana Churak-ova ◽  
Aygul Moldobayeva ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Antigenic Modulation ◽  
Antibody Targeting

scholarly journals Angiotensin-Converting Enzyme C-Terminal Catalytic Domain Is the Main Site of Angiotensin I Cleavage In Vivo

Hypertension ◽  
2008 ◽  
Vol 51 (2) ◽  
pp. 267-274 ◽  
Author(s):  
Sebastien Fuchs ◽  
Hong D. Xiao ◽  
Christine Hubert ◽  
Annie Michaud ◽  
Duncan J. Campbell ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Catalytic Domain ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Main Site

DOCKING STUDY OF NOVEL N-SUBSTITUTED 2,5-BIS[(7-CHLOROQUINOLIN-4-YL)AMINO]PENTANOIC DERIVATIVES AS SELECTIVE HIGH-BINDER WITH ANGIOTENSIN CONVERTING ENZYME 2

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (08) ◽  
pp. 16-24
Author(s):  
Mohammed Oday Ezzat ◽  
Basma M. Abd Razik ◽  
Kutayba F. Dawood
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Active Site ◽  
Docking Study ◽  
World Health ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Pharmaceutical Properties ◽  
Novel Coronavirus

The prevalence of a novel coronavirus (2019-nCoV) in the last few months represents a serious threat as a world health emergency concern. Angiotensin-converting enzyme 2 (ACE2) is the host cellular receptor for the respiratory syndrome of coronavirus epidemic in 2019 (2019-nCoV). In this work, the active site of ACE2 is successfully located by Sitmap prediction tool and validated by different marketed drugs. To design and discover new medical countermeasure drugs, we evaluate a total of 184 molecules of 7-chloro-N-methylquinolin-4-amine derivatives for binding affinity inside the crystal structure of ACE2 located active site. A novel series of N-substituted 2,5-bis[(7-chloroquinolin-4-yl)amino]pentanoic acid derivatives is generated and evaluated for a prospect as a lead compound for (2019-nCoV) medication with a docking score range of (-10.60 to -8.99) kcal/mol for the highest twenty derivatives. Moreover, the ADME pharmaceutical properties were evaluated for further proposed experimental evaluation in vitro or in vivo

Angiotensin-converting enzyme determination in plasma during therapy with converting enzyme inhibitor: two methods compared

1991 ◽  
Vol 37 (8) ◽  
pp. 1390-1393 ◽  
Author(s):  
T P Gorski ◽  
D J Campbell
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Spectrophotometric Method ◽  
Enzyme Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Fluorometric Method ◽  
Converting Enzyme Inhibitor ◽  
Ace Activity

Abstract For normal and above-normal concentrations of angiotensin-converting enzyme (ACE; EC 3.4.15.1) activity in plasma, results of a manual fluorometric method [with hippuryl-histidyl-leucine (HHL), 5 mmol/L, as substrate] correlated well with those of an automated spectrophotometric method [with 3-(2-furylacryloyl)-L-phenylalanyl-glycyl-glycine (FAPGG), 2 mmol/L, as substrate]. However, for patients receiving converting enzyme inhibitor (CEI) therapy, the spectrophotometric method showed much greater suppression of plasma ACE activity than did the fluorometric method. To determine which of the two methods provided a more reliable indication of ACE inhibition in vivo, we measured plasma ACE, angiotensin I (ANG I), and angiotensin II (ANG II) in patients receiving the CEI perindopril. During perindopril therapy, changes in the ratio of ANG II:ANG I, an index of ACE activity in vivo, showed a close agreement with changes in plasma ACE activity measured with FAPGG as substrate, but not with HHL as substrate. We conclude that measurement of ACE activity in vitro with FAPGG as substrate provides a reliable measure of changes in conversion of ANG I to ANG II in vivo during CEI therapy.

Sign in / Sign up

Export Citation Format

Share Document