Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was carried out to examine whether nitrofurantoin-induced pulmonary toxicity in normal rats was mediated via oxidant stress mechanisms. The relative importance of the cellular antioxidant enzymes in nitrofurantoin toxicity was also assessed. For this, the pulmonary toxicity induced by nitrofurantoin in rats was evaluated at various time intervals after a single subcutaneous injection. Data from this study showed that nitrofurantoin (200 mg/kg, s.c.) resulted in transient but measurable lung damage as evidenced by the increases in wet lung weight/body weight ratio and decreases in lung angiotensin converting enzyme activity. A transient decrease in GSH concentrations with a concurrent increase in GSSG concentrations as well as an increase in lipid peroxidation levels (measured by the formation of diene conjugates and thiobarbituric acid reactants) were also evident in lungs of nitrofurantoin-treated rats. In addition, nitrofurantoin did not alter the pulmonary superoxide dismutase and glutathione peroxidase activities, but it did produce transient decreases in catalase and glutathione reductase activities. These data indicate that impairment of the ability of the lung to detoxify reactive oxygen species may play an important role in the development of nitrofurantoin-induced pulmonary toxicity. The results of the present study suggest that nitrofurantoin can damage the lungs of rats, probably through oxidative stress-mediated mechanisms. Also, our data have provided in vivo evidence for substantiating lipid peroxidation as a possible cause of lung damage.
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PMID:Nitrofurantoin-induced pulmonary toxicity. In vivo evidence for oxidative stress-mediated mechanisms. 131 37

It is well known that pulmonary influx of neutrophils is involved in lung injury in patients with adult respiratory distress syndrome (ARDS). Neutrophils are major contributors to the self-defence mechanism, however, adverse effects of neutrophils have also been recognized. Recently, we found that a highly toxic substance, 9, 10-epoxy-12-octadecenoate (leukotoxin) is biosynthesized by human neutrophils. This study was designed to investigate whether or not leukotoxin participates in lung injury in ARDS and coagulation abnormality which is often associated with ARDS. Intravenous injection of leukotoxin (100 mumol/kg) caused acute edematous lung injury, which was evidenced by increased lung weight, albumin concentrations, and angiotensin converting enzyme activities in lung lavages. Pulmonary capillary endothelial damage and pulmonary edema were observed by electron microscopy. Moreover, considerable amounts of leukotoxin were detected in lung lavage fluid of rats exposed to pure oxygen for 60 h and patients with ARDS. An increased number of neutrophils and albumin concentrations were also observed in these lavage fluids. Intravenous injection of leukotoxin (100 mumol/kg) induced coagulation abnormalities such as disseminated intravascular coagulation. Increased levels of plasma leukotoxin were detected in ARDS patients with coagulation abnormalities. These results suggest that leukotoxin biosynthesized by neutrophils is an important contributor to lung injury in ARDS and associated coagulation abnormalities.
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PMID:[ARDS and leukotoxin]. 185 3

The activity of angiotensin converting enzyme (ACE) released into the culture medium of human umbilical cord vein endothelial cells in culture (HUVEC) for 24-hour incubation with or without various serotypes of lipopolysaccharide (LPS) was unchanged. ACE activity, however, in cell lysate or monolayer HUVEC after 24-hour incubation of various serotypes of LPS except LPS from E. coli, 026:B6, showed significant decrease, compared with no LPS treatment. Cell lysate contained much higher ACE activity than monolayer HUVEC after 24-hour incubation with or without LPS. These findings give rise to speculation that ACE or ACE-like substance might be located not only on the luminal surface, but also in cytoplasm of HUVEC, and also that decrease of ACE activity in the serum of septic adult respiratory distress syndrome (ARDS) patients might be due to reduced synthesis by vascular endothelial cells.
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PMID:[Influence of lipopolysaccharide on angiotensin converting enzyme activity expressed by human umbilical vein endothelial cells in culture]. 217 53

In spite of the development of various antibiotics, management of elderly patients with pneumonia remains an important problem. It is suggested that adult respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) often occur in elderly patients with pneumonia. Although neutrophils are suggested to be involved in the genesis of these conditions, details remain unknown. We demonstrated that a highly cytotoxic substance, 9,10-epoxy-12-octadecenoate, is biosynthesized from linoleate by human neutrophils, thus it was named leukotoxin. Leukotoxin was detected in lung lavages from patients with ARDS. In these lung lavages, increases in albumin concentration and angiotensin converting enzyme (ACE) activity were also observed. Similar results were observed in lung lavages from rats after exposure to hyperoxia for 60 hours in an experimental model of ARDS. Intravenous administration of leukotoxin (100 mumol/kg) caused lung edema. Albumin concentration and ACE activity were increased in lung lavages of rats receiving leukotoxin. In contrast, these changes were not observed in rats administered with linoleate. Furthermore, administration of leukotoxin (100 mumol/kg) caused coagulation abnormality, i.e., increase in fibrin-fibrinogen degradation products, decrease in fibrinogen, and prolongation of activated partial thromboplastin time and prothrombin time. Administration of linoleate did not induce these changes. It is indicated that O2- was produced by respiratory burst enzyme located in neutrophil plasma membrane, and that hydroxyl radicals derived from O2- by Fenton reaction were responsible for leukotoxin synthesis. From our results, leukotoxin, a product of hydroxyl radicals and linoleate, might be responsible for the genesis of ARDS and DIC.
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PMID:[Leukotoxin and pulmonary injury]. 238 90

The time course of the components of the renin-angiotensin system was investigated in the plasma of three patients on the intensive care unit. Two of them, which were both polytraumatized, suffered from adult respiratory distress syndrome (ARDS). All patients had sepsis and impaired pulmonary and renal function. Plasma samples were investigated for up to two weeks, in which time all three patients showed a decrease in their angiotensin converting enzyme (ACE) plasma concentration. Two of the patients with deteriorating renal function had three to four times elevated angiotensinogen (Ao) plasma levels, which were measured by both the direct and indirect radioimmunoassay. The ratio of the mean values between both assays was 1:1 in two patients and shifted to higher values in the direct assay in the third patient. This suggests that higher amounts of des-AngI-angiotensinogen were present in the latter patient, because "inactive" Ao is also detected by the direct assay. The decrease in active Ao may be caused by an up to twenty times elevated plasma renin activity (PRA). The PRA was correlated with the angiotensin I (AngI) plasma levels. However, at PRA values higher than 200 pmol AngI/ml/h this correlation decreased because of the rapid substrate consumption. In addition there was a good correlation between AngI and AngII plasma levels in two patients which could not be observed in the patient with the highest PRA and AngII values. A relationship between plasma ACE concentration and AngII formation could not be observed. Thus in two of the three septic patients the components of the renin angiotensin system were extremely stimulated at very low blood pressure values. These data show, that it is reasonable to follow the time course of the components of the renin angiotensin system in single patients. In addition it is demonstrated that the direct measurement of Ao is a valid supplement in the diagnosis of the renin angiotensin system.
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PMID:Renin-angiotensin system in sepsis. 282 Jun 28

The authors present a simple and clinically applicable method for the serial monitoring of pulmonary microvascular enzyme function in vivo. This method requires the intravenous injection of trace amounts of a radiolabelled substrate and the collection of a single arterial blood sample. Simultaneous measurement of pulmonary blood flow, (e.g., by dye- or thermo-dilution) and the determination of blood hematocrit are also needed for the calculations. This method was compared to the multiple blood sample indicator dilution method in normal anesthesized rabbits. Both methods gave identical results for the metabolism of the synthetic, hemodynamically inactive tripeptide, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP), by pulmonary microvascular endothelial angiotensin converting enzyme. The parameters measured were: 1) substrate utilization, expressed linearly and logarithmically, and 2) the apparent first order reaction constant. The new method was also used for the simultaneous measurement of single pass, transpulmonary metabolism of 3H-BPAP by angiotensin converting enzyme and of 5'-adenosine monophosphate by 5'-nucleotidase in rabbits in vivo. The authors propose that similar enzyme kinetic measurements could be used in clinical studies to test their usefulness as an aid in the early diagnosis of incipient pulmonary endothelial dysfunction, e.g., adult respiratory distress syndrome.
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PMID:Monitoring of pulmonary endothelial enzyme function: an animal model for a simplified clinically applicable procedure. 282 40

Serum angiotensin converting enzyme (serum ACE) levels and plasma fibronectin levels were measured daily in 46 septic patients during a ten day period. Thirty-eight patients developed ARDS; 28 survived (group 1), ten died (group 2), eight patients had no features of ARDS and survived (group 3). Sequential measurements of ACE and fibronectin levels were compared and plotted against indexes of respiratory impairment: PaO2 max Qs/Qt, static compliance and VD/VA ratio. These indexes were taken as criteria of weaning from controlled ventilation. During ARDS (groups 1 and 2), serum ACE levels decreased and were closely correlated with the severity of lung injury. Persistently decreased levels after eight days were consistent with continuing injury or lack of endothelial repair. On the other hand, plasma fibronectin levels increased throughout the study in survivors (group 1 and 3) and decreased in the group with fatal ARDS only (group 2). These results indicate that serum ACE levels might be a good index of endothelial injury and repair during ARDS and fibronectin a better index for evolution of sepsis and vital prognosis.
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PMID:Compared evolution of plasma fibronectin and angiotensin-converting enzyme levels in septic ARDS. 298 57

Acute pulmonary oedema can be induced by intraperitoneal injection of Escherichia coli endotoxin in the mouse. A fall in serum angiotensin converting enzyme activity is found in mice given endotoxin and in patients with septic adult respiratory distress syndrome, and has been proposed as an indicator of lung microvascular injury. Protein concentration and angiotensin converting enzyme activity in serum, lung, and bronchoalveolar lavage fluid were determined in male mice up to eight hours after injection of endotoxin. By six hours the serum protein concentration had increased and the bronchoalveolar lavage fluid protein concentration had fallen, suggesting fluid shift into the lung. Angiotensin converting enzyme activity fell in serum and lung but increased in bronchoalveolar lavage fluid. As these changes in enzyme activity were not paralleled by changes in protein concentration they are unlikely to be a result of fluid shift or protein leak, and may indicate an active role of the enzyme in the response to sepsis.
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PMID:Angiotensin converting enzyme and endotoxin induced lung damage in the mouse. 299 46

Decreased angiotensin converting enzyme (ACE) activity is a common finding in patients with adult respiratory distress syndrome and in animal models of lung injury. The nature of this effect is unknown. Intravascular fibrin, also a common finding in lung injury, is degraded to small peptides by proteolytic enzymes. Peptide 6A, corresponding to amino acid residues 43 to 47 of the B beta chain of fibrin(ogen), is produced by plasmin degradation of fibrin and has been shown to inhibit ACE in vitro. We investigated the effect of this peptide on the pulmonary hydrolysis of a synthetic ACE substrate, benzoyl-phenylalanyl-alanyl-proline, in anesthetized rabbits and in isolated, perfused rabbit lungs. Peptide 6A caused a reversible, dose-dependent inhibition of benzoyl-phenylalanyl-alanyl-proline hydrolysis. It also potentiated the increase in pulmonary arterial pressure and the decrease in systemic arterial pressure due to bradykinin (BK), as well as the increase in pulmonary artery pressure due to BK in isolated lungs. The amount of BK needed to increase pulmonary arterial pressure was about 1000-fold larger in the isolated lung than in the intact animal. Peptides of this type might contribute to decreased ACE activity in patients with adult respiratory distress syndrome and may potentiate BK-mediated hemodynamic changes in these patients.
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PMID:Effect of a fibrin-derived vasoactive peptide on pulmonary angiotensin converting enzyme activity and on pressure responses to bradykinin. 369 36

Serum angiotensin converting enzyme (ACE) levels were obtained in 24 control patients who were critically ill, in 11 patients with cardiogenic pulmonary edema, in 8 patients with status postcardiopulmonary bypass, and in 12 patients with adult respiratory distress syndrome (ARDS). Mean values in cardiogenic pulmonary edema (24.3 +/- 3.9 SD) in cardiopulmonary bypass (19.5 +/- 3.1) and in patients with ARDS and no sepsis (n = 7, 19.0 +/- 5.5) were not significantly different from controls (20.7 +/- 2.8). In contrast, patients with ARDS and sepsis had markedly decreased serum ACE levels which fell outside of control range (n = 5, 8.6 +/- 2.3). The authors speculate that decreased ACE levels in the combination of sepsis and ARDS are due to the presence of circulating inhibitors of ACE. The finding of decreased serum ACE can be of potential clinical usefulness by raising the possibility of sepsis as the etiology of ARDS before results of blood cultures are available.
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PMID:Decreased serum angiotensin converting enzyme in adult respiratory distress syndrome associated with sepsis: a preliminary report. 626 54


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