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 effects of early-stage hypertension on the macromolecular transport characteristics of the aorta have been investigated in rats 1 week after the ligature of the abdominal aorta between the two renal arteries. The animals were left untreated or treated for 1 week with an angiotensin converting enzyme inhibitor (enalapril, 6 mg/kg per day). Blood pressure of a subgroup of hypertensive rats was acutely lowered to a normal level by injection of enalaprilat (1.5 mg/kg) at the time of the experiment. 131I-Albumin and 125I-albumin were injected 90 minutes and 5 minutes, respectively, before the rats were killed. The transmural distribution of the relative tissue concentrations across the wall was obtained using a serial frozen-section technique. Short-term albumin uptake permitted calculation of apparent endothelial permeability coefficients, and 90-minute uptake was used to estimate the steady-state albumin distribution within the media. The effect of early-stage hypertension on the characteristics of the arterial macromolecular transport depended on the aortic site; the ascending aortic arch appeared not to be affected. In the thoracic and abdominal aorta, the endothelial permeability coefficients increased significantly in hypertensive rats. This increase was not a direct effect of the arterial pressure, since the values were not significantly different when the pressure was acutely normalized. The 90-minute albumin concentration in the media was enhanced in hypertensive rats and returned to the normal value by acutely lowering the blood pressure, indicating that the increase observed in hypertensive rats resulted from a direct effect of pressure, possibly increased pressure-driven convection and/or pressure-induced stretching of the wall. Treatment by angiotensin converting enzyme inhibitor prevented hypertension and protected against its effects in hypertensive animals.
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PMID:Albumin transport characteristics of rat aorta in early phase of hypertension. 151 64

Albumin and immunoglobulin G (IgG) show increased visible fluorescence in diabetic patients, IgG fluorescence being correlated with the presence of diabetic retinopathy. Captopril, an angiotensin converting enzyme (ACE) inhibitor, has free radical scavenging ability, attributable to its thiol group. We compared the scavenging effect of captopril (at doses between 0.5 and 100 microM) with perindoprilat, enalapril and enalaprilat (ACE inhibitors without scavenging ability) and two thiol-containing compounds, mercaptopropionylglycine (MPG) and N-acetylcysteine (NAC) (scavengers with no effect on ACE). Three systems were used to generate visible fluorescence in albumin and IgG; glycation, exposure to copper/hydrogen peroxide and gamma radiation. All three thiol-containing compounds inhibited fluorescence development in IgG and albumin, when fluorescence was generated by glycation or gamma radiation. Other ACE inhibitors had no effect with IgG. Enalapril and perindoprilat showed less effect than captopril with albumin; enalaprilat had no effect. No compound had any effect on fluorescence generation by copper/hydrogen peroxide. Captopril may have an additional antioxidant effect compared to other ACE inhibitors.
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PMID:Captopril inhibits the fluorescence development associated with glycation of proteins. 152 7

A clinical trial, to evaluate the effects of a Chinese herbal drug, Rheum E and angiotensin converting enzyme inhibitor, Captopril on chronic renal failure (CRF), was conducted. Thirty cases with initial serum creatinine (Scr) levels of 344.8 +/- 114.0 mumol/L were allocated randomly to 3 groups: Rheum E treated group, Captopril treated group and Rheum E + Captopril group. A control group of 12 cases were on dietary therapy alone. During the 6-22 months of treatment, all the patients were kept on low-protein (0.6g/kg/d), and low-phosphorus (10mg/kg/d) diet. The results showed that the progression rate of renal failure, calculated by regression analysis of 1/Scr vs time, was found to be retarded after treatment with the increased regression coefficient (b value). Scr levels and blood urea nitrogen were kept stable or fell slightly. Albumin rose during the follow-up period (P less than 0.05) in the treated patients, being more marked in both Rheum E and Rheum E + Captopril groups. Uremic symptoms of nausea, anorexia improved in most of the treated patients. It is concluded that long-term low-dose Rheum E taken orally is beneficial to CRF. Its effect is better than that of Captopril. The regime of Rheum E and Captopril is a preferable choice in the long-term treatment for preventing progression of CRF.
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PMID:Clinical effects of rheum and captopril on preventing progression of chronic renal failure. 212 52

Selected functions of alveolar macrophages obtained by bronchoalveolar lavage of 12 healthy smokers were examined before and after eight weeks' treatment with an inhaled glucocorticosteroid, budesonide (400 micrograms twice daily). After budesonide treatment spontaneous as well as opsonised zymosan triggered prostaglandin E2 (PGE2) secretion from harvested cells was reduced; no such reduction in opsonised zymosan triggered leukotriene B4 (LTB4) production was observed. Neither the capacity to phagocytose opsonised yeast particles nor the superoxide radical generation triggered by the calcium ionophore A23187, 4 beta-phorbol 12-myristate 13-acetate (PMA), or opsonised zymosan ex vivo were more than marginally affected by the glucocorticosteroid treatment in vivo. Lavage fluid concentrations of angiotensin converting enzyme (ACE), however, after treatment were twice those before treatment and concentrations of fibronectin were reduced to half. Albumin concentrations in lavage fluid were not affected by the glucocorticosteroid treatment. In separate experiments treatment of alveolar macrophages with 10(-7) or 10(-6) M budesonide overnight in vitro did not affect their superoxide radical or PGE2 generation but significantly blocked LTB4 release. These data indicate that inhaled gluco-corticosteroid treatment may affect synthesis or release (or both) of ACE and fibronectin by alveolar macrophages from healthy smokers whereas other functions of these cells, such as the generation of reactive oxygen derived products ex vivo, are only marginally affected.
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PMID:Effects of an inhaled corticosteroid, budesonide, on alveolar macrophage function in smokers. 216 59

The effect of enalapril on albumin excretion rate was studied in two groups of age- and sex-matched Type 1 (insulin-dependent) diabetic patients, aged 15-20 years, with persistent microalbuminuria greater than 20 micrograms/min. Group 1 contained six patients with systolic blood pressure greater than or equal to 75th percentile for age and sex, group 2 six normotensive patients. Enalapril (10-20 mg/day) was given for six months. Albumin excretion rate, glomerular filtration rate, renal plasma flow, blood pressure at rest and during exercise, and angiotensin converting enzyme activity were measured before, after three weeks' and six months' treatment and six months after treatment withdrawal. Albumin excretion rate decreased in all patients after three weeks' (mean decreases 55% in group 1, 65% in group 2) and six months' treatment (35% in group 1, 61% in group 2). Systolic blood pressure remained unchanged in both groups. Diastolic pressure was reduced after three weeks in group 1 (p = 0.001). No reduction in increment in systolic pressure during exercise test occurred in any group during treatment. Angiotensin converting enzyme activity decreased in all patients after three weeks (p = 0.001) and six months (p = 0.003). This correlated to the decrease in albumin excretion rate after three weeks (r = 0.79, p = 0.05) and six months (r = 0.59, p = 0.04). HbA1c, mean blood glucose and glomerular filtration rate remained unchanged during the study in both groups. Renal plasma flow tended to increase after three weeks' and six months' treatment in group 2 (p = 0.06, respectively) but not in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enalapril reduces microalbuminuria in young normotensive type 1 (insulin-dependent) diabetic patients irrespective of its hypotensive effect. 217 Feb 18

We have studied the in vitro interactions versus some blood components of the hemoglobin niosomes whose preparation and physicochemical and oxyphoric properties have been published in a precedent paper (this journal, 1989, No. 7, p. 192). This work was devoted to the research of 1) Agglutination phenomena with ABO blood group substances, plasma, some of its components and three plasma expanders, finally main erythrocytic phenotypes. 2) Adsorption of plasma proteins by immunoelectrophoresis. 3) Effects of niosomes on blood coagulation by thromboelastography. 4) Interactions between niosomes and phagocytes by electron microscopy, chemotactic migration, oxygen consumption, superoxide generation and oxydases function. These assays allow to observe and conclude that: 1) The agglutination phenomena are almost constant except with red blood cells. The agglutinates are dissociable by shaking. The agglutination appears to be nonspecific of a niosome component but is not observed with "classical" DPPC-chol-DCP liposomes. 2) Albumin and eventually transferrin are adsorbed at the surface of niosomes but without destabilizing them. 3) The vesicules show no important effects on coagulation factors, the enhancement of clotting time appearing essentially the consequence of blood dilution. 4) Niosomes phagocytosis is important but all the measurements fail to show any cellular metabolism activation: cell oxygen consumption, oxygenated metabolites generation and oxydases activity are not enhanced whatever the "electric" charge or the niosomes/phagocytes ratio used.
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PMID:[Hemoglobin niosomes. II. In vitro interactions of plasma proteins and phagocytes]. 218 79

It has been proposed that lowering glomerular pressure in children with insulin-dependent diabetes mellitus will reduce microalbuminuria and that this reduction may preserve renal function. We therefore conducted a double-blind, placebo-controlled, crossover trial to compare 3 months of treatment with the angiotensin converting enzyme inhibitor captopril (0.9 mg/kg/day), and 3 months of placebo administration to 12 normotensive adolescents with insulin-dependent diabetes mellitus, 11 with microalbuminuria (albumin excretion rate of 15 to 200 micrograms/min) and one with early overt nephropathy. Mean age (+/- SD) was 14.4 +/- 1.7 years, and disease duration was 5.1 +/- 2.5 years. Albumin excretion rate decreased significantly during captopril therapy (baseline 78 +/- 114 micrograms/min; mean of monthly measurements 38 +/- 55 micrograms/min vs placebo 78 +/- 140 micrograms/min; p less than 0.001). During captopril therapy, albumin excretion was reduced by 41 +/- 44% and decreased in 10 of 12 subjects, but was unchanged in two, one with a borderline albumin excretion rate (16.3 micrograms/min) and one with diabetes of short duration (2.9 years). Plasma renin activity rose significantly during captopril therapy, and mean arterial pressure decreased slightly (placebo 81 +/- 7 mm Hg; captopril 76 +/- 5 mm Hg; p = 0.004). After 3 months of captopril treatment, glomerular filtration rate and renal plasma flow did not change significantly. Hemoglobin Alc values remained stable during the study. The only side effect of captopril was diarrhea in one patient. We conclude that, in the short term, captopril is effective in decreasing albumin excretion rate in normotensive children with insulin-dependent diabetes mellitus and microalbuminuria, without significant side effects. Longer trials are indicated in an attempt to delay or prevent overt nephropathy.
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PMID:Angiotensin converting enzyme inhibitor therapy to decrease microalbuminuria in normotensive children with insulin-dependent diabetes mellitus. 219 59

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

We have observed that neutrophils biosynthesize linoleate epoxide, 9,10-epoxy-12-octadecenoate, and have named it leukotoxin because of its cytotoxic effect. In this experiment, the effect of leukotoxin on the lung was investigated. Acute effect of leukotoxin: Using Wistar rats, leukotoxin (100 mumol/kg) was injected intravenously for the leukotoxin group, and linoleate (100 mumol/kg) for the linoleate group. Physiological saline was injected as the control. Ten min after injection, rats were divided into 3 groups: (1) lungs were isolated, and lung wet weight, and dry weight were measured; (2) lung lavages were performed, and albumin concentration and activity of angiotensin converting enzyme (ACE) were measured; (3) morphological changes were studied by light and electron microscope. After administration of leukotoxin, lung wet weight/body weight ratios and dry weight/wet weight ratios were increased. Albumin concentration and ACE activity in lung lavages were also increased. Pulmonary edema was also confirmed by light microscopic findings. Alveolar epithelial cell damage and endothelium damage were also observed. Linoleate had no significant effect on these biochemical parameters and morphological findings. Subacute effect of leukotoxin: Twelve hr after administration of leukotoxin (50 mumol/kg) or linoleate (50 mumol/kg), the same studies were performed as in the acute experiments. Immediately after administration of leukotoxin, no significant effect was observed. However, 12 hr later similar changes were observed as in the acute experiments. Linoleate did not show any significant effect 12 hr after injection. These results indicate that leukotoxin biosynthesized by neutrophils might be closely related to the genesis of inflammatory edema.
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PMID:Neutrophil-derived epoxide, 9,10-epoxy-12-octadecenoate, induces pulmonary edema. 314 92

Nephropathy is a frequent complication of long term diabetes. Diabetic nephropathy is the major determinant of premature morbidity and mortality both in insulin-dependent (IDDM) and in non-insulin dependent-diabetes mellitus (NIDDM). There is good evidence that genetic predisposition plays a major role in development of diabetic nephropathy. This hypothesis is based on the observation that diabetic nephropathy clusters within families, both in IDDM and NIDDM. Components of the renin-angiotensin system (RAS) are plausible candidate genes to examine for a association with microalbuminuria and diabetic nephropathy. In this study we compared the distribution of PstI melting polymorphism at the ACE locus among NIDDM patients with diabetic nephropathy and in patients who, despite long duration of NIDDM, remain without this complication. The 220 NIDDM patients for whom DNA was available were classified into two groups according to their renal status: normoalbuminuric control subjects (n = 80) who are NIDDM patients with an A/C ratio < 2.5 and nephropathy cases (n = 140) who are NIDDM patients with A/C ratio > 2.5. Albumin excretion rate was assayed by radioimmunoassay. HbA1c was assayed using HPLC methods, creatinine--using Jaffe methods and DNA analysis using PCR reaction, and then after the amplification product was digested with PstI enzyme. The study revealed that PstI sequence differences ("+/= and -") in the ACE gene do not contribute to genetic susceptibility to diabetic nephropathy in NIDDM.
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PMID:[Is PstI polymorphism of the angiotensin I converting enzyme gene associated with nephropathy development in non-insulin-dependent diabetes mellitus (preliminary study)]. 949 4


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