Kinetics of inhibition of angiotensin converting enzyme by captopril and by enalapril diacid

1984 ◽  
Vol 33 (8) ◽  
pp. 1273-1276 ◽  
Author(s):  
C.Hugh Reynolds
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Kinetics Of ◽  
Kinetics Of Inhibition

scholarly journals The behaviour of leucine aminopeptidase towards thionopeptides

1987 ◽  
Vol 245 (1) ◽  
pp. 285-288 ◽  
Author(s):  
R E Beattie ◽  
D T Elmore ◽  
C H Williams ◽  
D J S Guthrie
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Leucine Aminopeptidase ◽  
Converting Enzyme ◽  
Carboxypeptidase A ◽  
Inhibitory Potency ◽  
Pig Kidney ◽  
Competitive Inhibitors ◽  
Kinetics Of ◽  
Kinetics Of Inhibition

Thionoleucine S-anilide (Leut-anilide), Leut-Gly-OEt and Leut-Phe-OMe were synthesized and shown to be competitive inhibitors of leucine aminopeptidase from pig kidney. The kinetics of inhibition were determined in the presence of leucine 4-methylcoumarin-7-amide as substrate. Although the compounds showed only moderate inhibitory potency, it was found that all were resistant to hydrolysis by the enzyme, in contrast with the reported behaviour of some thionopeptide analogues of substrates for other Zn2+-peptidases such as carboxypeptidase A and angiotensin-converting enzyme.

Angiotensin converting enzyme in brush-border membranes of avian small intestine

1988 ◽  
Vol 135 (1) ◽  
pp. 1-8
Author(s):  
B. R. Stevens ◽  
A. Fernandez ◽  
C. del Rio Martinez
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Brush Border ◽  
Physiological Role ◽  
Intestinal Epithelial ◽  
Converting Enzyme ◽  
Brush Border Membranes ◽  
Fluid Uptake ◽  
The Common ◽  
Kinetics Of ◽  
Hydrolysis Of

Angiotensin converting enzyme activity was identified in brush-border membranes purified from the small intestinal epithelium of the common grackle, Quiscalus quiscula. Angiotensin converting enzyme was enriched 20-fold in the membrane preparation, compared with intestinal epithelial cell scrapes, and was coenriched with the brush-border markers, alkaline phosphatase and aminopeptidase N. The kinetics of hydrolysis of N-[3-(2-furyl)acryloyl]-L-phenylalanylglycylglycine (FAPGG) gave a Vmax of 907 +/− 41 units g-1 and a Km of 55 +/− 6 mumol l-1. The avian intestinal angiotensin converting enzyme was inhibited by the antihypertensive drug, Ramipril, with a median inhibitory concentration (IC50) of 1 nmol l-1. In the light of previous studies on angiotensin converting enzyme in mammalian epithelia, these results may implicate a physiological role for angiotensin converting enzyme in regulating electrolyte and fluid uptake in bird small intestines.

Effects of gas composition and pH on kinetics of lung angiotensin-converting enzyme

1987 ◽  
Vol 62 (3) ◽  
pp. 1216-1221 ◽  
Author(s):  
D. A. Rickaby ◽  
R. D. Bongard ◽  
M. J. Tristani ◽  
J. H. Linehan ◽  
C. A. Dawson
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Surface Area ◽  
Ph Dependence ◽  
Gas Composition ◽  
Converting Enzyme ◽  
Hydrolysis Process ◽  
Hypoxic Vasoconstriction ◽  
Ace Activity ◽  
Kinetics Of ◽  
Hydrolysis Of

Given the pH dependence of enzymes in general and the potential importance of a blood and alveolar gas composition dependency on the interpretation of changes in the hydrolysis of angiotensin-converting enzyme (ACE) substrates by pulmonary endothelial ACE, we examined the influence of Pco2 and Po2 on the hydrolysis of a synthetic ACE substrate (benzoyl-phenylalanyl-alanyl-proline, BPAP) on passage through isolated rabbit lungs. Perfusate pH values of about 7.1, 7.4, and 7.9 were obtained by ventilating the lungs with gas containing different CO2 concentrations and Po2 values of approximately 110 and approximately 10 Torr were obtained by varying the concentration of O2 in the ventilating gas mixture. In the range studied neither acidosis nor alkalosis produced any significant changes in BPAP hydrolysis or in the kinetic parameters, Vmax and Km, for the hydrolysis process. On the other hand, a reduction in BPAP hydrolysis was detected when the Po2 was reduced from 110 to 10 Torr. The Vmax for BPAP hydrolysis by the lung was inversely correlated with the magnitude of the hypoxic vasoconstriction that occurred, suggesting that the reduced BPAP hydrolysis with hypoxia was due to the loss of perfused surface area due to the vasoconstriction. The results suggest that correlations between Pco2 and/or pH and whole-lung ACE activity that might occur in diseased lungs do not imply causalty. The hemodynamic consequences of changing Po2 (i.e., hypoxic vasoconstriction) may alter whole-organ ACE activity in the sense of changing the perfused surface area (i.e., the amount of ACE in contact with flowing perfusate).

Angiotensin-converting enzyme kinetics in an endothelial cell column

1990 ◽  
Vol 258 (4) ◽  
pp. L188-L194
Author(s):  
R. E. Howell ◽  
F. R. Haselton ◽  
S. N. Mueller
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Indicator Dilution ◽  
Converting Enzyme ◽  
Aortic Endothelial Cells ◽  
Metabolic Functions ◽  
Microcarrier Beads ◽  
Serial Samples ◽  
Kinetics Of

The kinetics of saturable endothelial metabolic functions have been assessed in vivo by transient (indicator-dilution) measurements and in culture by steady-state measurements, but comparisons between the two are difficult. Therefore, we used indicator-dilution methods to assess the kinetics of angiotensin-converting enzyme (ACE) activity in cultured endothelium. Bovine fetal aortic endothelial cells were grown to confluence on microcarrier beads. Cell-covered beads were poured into polypropylene columns and perfused with serum-free culture medium. Six injections, containing [3H]benzol-Phe-Ala-Pro [( 3H]BPAP, an ACE substrate) and varying amounts of unlabeled BPAP, were applied to each column and effluent was collected in serial samples. The apparent kinetics of BPAP metabolism were determined by four models used previously to determine pulmonary endothelial ACE kinetics in vivo, the most useful model incorporating transit time heterogeneity. The Km averaged 5 microM, which is close to values determined previously in vivo and in vitro. The Amax (Vmax.reaction volume) and Amax/Km averaged 6 nmol/min and 1.5 ml/min, respectively, which are lower than estimates in vivo. In conclusion, we have developed a new method for investigating saturable metabolic activity in cultured endothelium, which after further exploration should also enable better comparisons of endothelial metabolic functions in vivo and in culture.

Kinetics of pulmonary angiotensin-converting enzyme activity in conscious developing lambs

1984 ◽  
Vol 57 (4) ◽  
pp. 1158-1166 ◽  
Author(s):  
B. R. Pitt ◽  
G. Lister
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Maximum Velocity ◽  
Indicator Dilution ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme Activity ◽  
Alveolar Hypoxia ◽  
Pass Through ◽  
The Right ◽  
Kinetics Of ◽  
Indicator Dilution Techniques

Apparent enzyme kinetics were determined for pulmonary angiotensin-converting enzyme (ACE) as a function of postnatal development and alveolar hypoxia in intact conscious lambs (9 newborn and 7 sheep, 8–23 wk). We injected into the right atrium a mixture of indocyanine green and 3H-labeled benzoyl-phenylalanyl-alanyl-proline (BPAP), a synthetic substrate for ACE, and sampled blood from the aorta at 1-s intervals. From this, we quantified the %BPAP metabolism during a single pass through the lungs by use of indicator-dilution techniques. By adding unlabeled BPAP to the injectate, combining outflow data from two to three measurements, and applying a nonlinear model of pulmonary metabolism (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51:405–414, 1981), we could determine 1) apparent maximum velocity (Vmax); 2) concentration at which velocity was one-half Vmax (Km); and 3) alpha, a measure of perfusion heterogeneity. All animals were studied during normoxia and while breathing 10% O2 for at least 15 min. Seven of the newborn lambs were studied 1 wk later. Km in the newborn was 15 +/- 3 microM and did not change significantly with age or hypoxia. Vmax increased markedly with development (newborn: 14 +/- 2 nmol X s-1 X g dry lung-1; sheep: 38 +/- 5 nmol X s-1 X g dry lung-1; P less than 0.01). Alveolar hypoxia significantly decreased Vmax in the newborn only (P less than 0.05); there was no significant change in Vmax in the same animal studied 1 wk later or in the older group.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo measurements of pulmonary angiotensin-converting enzyme kinetics. I. Theory and error analysis

1995 ◽  
Vol 78 (3) ◽  
pp. 1158-1168 ◽  
Author(s):  
J. Markham ◽  
T. J. McCarthy ◽  
M. J. Welch ◽  
D. P. Schuster
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Enzyme Kinetics ◽  
Kinetic Parameters ◽  
Converting Enzyme ◽  
Activity Data ◽  
Time Activity ◽  
Fast Kinetics ◽  
Trans Conformer ◽  
Kinetics Of

We developed a procedure for measuring pulmonary angiotensin-converting enzyme kinetics with fluorine-18 fluorocaptopril and positron emission tomography (PET). The method is based on the application of a compartmental receptor model that represents the kinetics of two species of ligand, presumably the trans and cis conformers of captopril. The input function was characterized and includes corrections for the labeled metabolites of fluorocaptopril. Application of the procedure to lung time-activity data obtained with PET produced estimates of kinetic parameters demonstrating fast kinetics for one conformer and slower kinetics for the other. Simulation studies were performed to evaluate the sensitivity of the estimated parameters to errors in the model assumptions and in measured values for variables required for analysis of the PET data. Estimates for two of the kinetic parameters, the amount of perfused unbound functional enzyme normalized to regional lung volume and the association rate constant for the trans conformer, were relatively stable even with large errors in the input data, varying < 30% from true values for all perturbations. Thus, the procedure produces reliable estimates of the kinetics of the trans conformer of captopril as well as theoretical curves that are close to the observed data.

DIFFERENTIAL CHANGESOF PLASMATIC MARKERS OF THE ENDOTHELIAL FOLLOWING dDAVP

1987 ◽  
Author(s):  
M L Scrobohaci ◽  
L Drouet ◽  
B Baudin ◽  
A Rodriguez
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Von Willebrand Factor ◽  
Protein S ◽  
Von Willebrand Disease ◽  
Plasminogen Activation ◽  
Converting Enzyme ◽  
Tissue Plasminogen ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Kinetics Of

Plasmatic levels of tissue plasminogen activation is commonly assumed to be of endothelial origin ; Angiotensin converting enzyme can be of endothelial or monocytic origin;Fibronectin is mostly from hepatic origin but endothelium can participate. Protein S is a newly recognized endothelial protein. Plasmatic von Willebrand factor is mostly from endothelial origin as the factor megakaryocytic origin is stored in platelet αd granules.dDAVP by indirect effect stimulates release of endothelial factors,13 patients with moderate von Willebrand disease were submitted to an infusion of 0.4 ug/kg dDAVP and were followed for four hours after infusion.Interstingly the kinetics of release of each of the studied factors is totally different.-Tissue plasminogen activator israpidly released and come back alsoquickly to its original level,- Release of von Willebrand factor is delayed comparatively to tPA and stayed for a longer time at increased level,- Angiotensin converting enzyme is not affected by dDAVP while its level is stimulated by veno-occlusion- Fibronectin and Protein S arenot significantly modified by dDAVPFrom these results mechanism of action of dDAVP cannot be hypothesized, but it seems evident that the release (and so the endothelial metabolism) of each of the studied factorsis different and not linked.

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