Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Two independent mutants of Escherichia coli deficient in dipeptidyl carboxypeptidase activity (Dep-) were isolated after mutagenesis with ethyl methanesulfonate. Mating experiments and introduction of specific episomes indicated that the responsible gene was located at approximately 27--31 min on the E. coli chromosome. The Dep- mutants differed from the parental strain in their inability to grow with N-acetylalanylalanylalanine as the sole nitrogen source. Revertants selected for growth on this substrate of the enzyme were found to have reacquired the activity. Enzyme activity was highly sensitive to inhibition by 1-(D-3-mercapto-2-methylpropanoyl)-L-proline (SQ 14225), a potent inhibitor of mammalian dipeptidyl carboxypeptidase (angiotensin-converting enzyme, peptidyl dipeptidase, EC 3.4.15.1). This compound also reduced the rate of growth of the wild type with N-acetylalanylalanylalanine but not with ammonium sulfate. A fraction of the enzyme was released into the medium by osmotic shock, indicating that its presence in the periplasmic space may account for growth with N-acetylated peptides that cannot be taken up by E. coli. In addition to providing information about the specific role of this exopeptidase in E. coli, the Dep- mutants may prove useful for delineating the regulation and cellular function of dipeptidyl carboxypeptidases in higher organisms.
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PMID:Escherichia coli mutants defective in dipeptidyl carboxypeptidase. 21 6

The acute and subacute toxicities of N-[8-amino-1(S)-carboxyoctyl]-L- alanyl-L-proline (AB-47, CAS 120008-53-9), which is a non-sulfhydryl angiotensin converting enzyme inhibitor, were studied in male and female Fischer 344 rats. In the acute study, male and female rats were orally given 5000 mg/kg of AB-47. No rats were dead during the observation period (14 days) after the administration. The LD50 values of AB-47 were more than 5000 mg/kg in both male and female rats. Although only diarrhoea as toxic sign was observed 2 to 7 h after the administration, this sign disappeared within 24 h after the administration. Necropsy at the termination of observations revealed no macroscopic lesions in any rats. In the subacute study, male and female Fischer 344 rats were orally given 40, 200 or 1000 mg/kg/d of AB-47 for 4 weeks. Neither toxic signs nor death due to drug effects were observed at any dosage levels of AB-47. Furthermore, AB-47 did not influence body weight, food consumption, food efficiency, urinalytical and hematological parameters in both male and female rats. The minor changes of serum parameters, which consisted of very slight increases in serum potassium and decreases in serum albumin/globulin ratio, occurred in male rats given 200 and 1000 mg/kg/d of AB-47. Serum urea nitrogen values were elevated in both male and female rats given 1000 mg/kg/d of AB-47. Slight decreases of heart weight and heart weight/body weight ratios were observed at all dosage levels of AB-47.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toxicity studies of the non-sulfhydryl angiotensin converting enzyme inhibitor N-[8-amino-1(S)-carboxyoctyl]-L-alanyl-L-proline in rats. 128 6

1. In previous studies a rat inhalation model was developed to investigate the treatment of acute nitrogen dioxide (NO2) intoxication. 2. Biochemical parameters, which may be important for the evaluation of lung injury and repair, were reviewed and compared with the histology. 3. After exposure to high NO2 concentrations (75 ppm, 125 ppm or 175 for 10 min) the lung injury observed by light microscope was most pronounced after 24 h and became worse with increasing concentration. 4. The most sensitive indicators for lung injury in the broncho-alveolar lavage fluid (BAL) were protein and albumin concentrations, angiotensin converting enzyme activity, beta-glucuronidase activity and the presence of neutrophil leucocytes. The changes observed in these variables were dose-dependent. Following exposure to 175 ppm the protein and albumin concentrations and the angiotensin converting enzyme activity showed a 100-fold increase, while the beta-glucuronidase activity showed a 10-fold increase. 5. Glucose-6-phosphate dehydrogenase and glutathione peroxidase in the supernatant of lung homogenate and gamma-glutamyl transferase activity in BAL are likely to be the most practical parameters for monitoring the phase of repair because their activities were maximal at the moment histological changes were reduced in intensity. 6. Repair was almost complete 7 d following exposure.
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PMID:Biochemical and histological alterations in rats after acute nitrogen dioxide intoxication. 135 14

The hypotensive efficacy of (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl) phosphinyl]oxy]-1-oxohexyl]-L-proline (SQ 29,852), a phosphorus-containing novel angiotensin converting enzyme inhibitor (ACEI) was examined in conscious two-kidney, one-clip Goldblatt hypertensive dogs. The acute hypotensive effect of SQ 29 852 was compared with that of captopril or enalapril at 3 mg/kg, p.o., for each, and the potencies were ranked as follows, enalapril greater than SQ 29,852 greater than captopril. On the other hand, the hypotension caused by repetitive dosing with SQ 29,852 (3 mg/kg, p.o./d for 7 d followed by another 7-d treatment with 10 mg/kg, p.o./d) was somewhat more marked than that by enalapril at the same dosage. Blood urea nitrogen (BUN) increased in all the animals given enalapril, while that in all of the SQ 29,852-treated animals did not increase. These results indicate that SQ 29,852 is a potent, and long-lasting ACEI with a possible low incidence of side effects.
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PMID:Hypotensive effect of a phosphorus-containing novel angiotensin converting enzyme inhibitor, (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl)phosphinyl] oxy]-1-oxohexyl]-L-proline (SQ 29,852) in conscious hypertensive dogs. 143 66

We retrospectively analysed the effects of a 12-month treatment with captopril (Tensiomin) in 46 patients. All of the patients had hypertension lasting for years (9 essential, 37 with chronic renal failure), 32 of them had proteinuria. Captopril was given in addition to, or in exchange for, other antihypertensive drugs. Under treatment with ACE-inhibitors, a small but significant decrease in diastolic blood pressure (0.4 torr/month) and in proteinuria (0.19 g/month) was seen (regression analysis). Discriminant analysis showed proteinuria and diastolic blood pressure to be the more modifiable, the younger the patients, the higher the proteinuria at the beginning and the longer the history of hypertension. Serum creatinine, blood urea nitrogen, serum protein and serum potassium did not change.
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PMID:[Effect of the ACE-inhibitor captopril on the blood pressure and kidney function of patients with essential and renal hypertension]. 177 7

The author studied the characteristics of ACE inhibitor-induced cough in 41 non-smoking hypertensive patients. For at least 6 months, 20 patients (10 males and 10 females) were treated with enalapril, and 21 (11 males and 10 females) with aracepril. The results were as follows. 1) ACE inhibitor-induced cough was induced in 7 cases (1 male and 6 females). The incident rate of cough was 17.1%. ACE inhibitor-induced cough was not significantly related to past allergic history or to the beta-adrenergic blocker therapy. The laboratory findings of the cough sufferers--such as eosinophil percent in venous blood, serum GOT and GPT, urea nitrogen, creatinine, renal function (PSP excretion test and creatinine clearance), and pulmonary function (%FVC, FEV1.0% and %V25)--were not significantly different from those of the non-coughers. 2) Inhibitory effects of ipratropium bromide inhalation of ACE inhibitor-induced cough were noted in 83.3% of the patients, but their coughs did not completely disappear. From these findings, the pathogenesis of this cough may be related to be as follows. The cough seems to be related to the release of acetylcholine from vagal nerve terminals or to the stimulation of irritant receptors and vagal reflex. 3) Chronic persistent cough or bronchial asthma did not occur after stopping the treatment with ACE inhibitors. The mean follow-up period was 15.6 months.
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PMID:[Angiotensin converting enzyme (ACE) inhibitor-induced cough in non-smoking hypertensive patients]. 183 7

The combination of environmental chamber exposure and bronchoalveolar lavage (BAL) was used to study the effects of the common air pollutant nitrogen dioxide (NO2). Eighteen healthy nonsmokers were exposed to NO2 during 20 min in an exposure chamber during light bicycle ergometer work. All subjects were examined with BAL at least 3 wks before exposure, as a reference. The subjects were re-examined with BAL, in groups of eight, 24 h after exposure to 4, 7 and 10 mg NO2.m.3 (2.25, 4.0 and 5.5 ppm), respectively. An inflammatory cell response was found after exposure to all concentrations. An increase in the number of lymphocytes in BAL fluid was observed after 7 and 10 mg.m.3 (p less than 0.05 and 0.02, respectively). An increase in the number of mast cells, that appears to be dose-dependent, was found after exposure to all concentrations. The proportion of lysozyme positive alveolar macrophages was elevated after exposure to 7 mg.m.3. The inflammatory mediators fibronectin, hyaluronan, angiotensin converting enzyme (ACE) and beta 2-microglobulin were unchanged by exposure. Due to the findings of inflammatory cell changes far below the peak exposure limits for work places in industrialized countries, 9-18 mg.m.3, the safety of these limits is questioned. Studies are in progress in our laboratory using BAL to evaluate the effects of repeated NO2 exposure.
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PMID:Inflammatory cell response in bronchoalveolar lavage fluid after nitrogen dioxide exposure of healthy subjects: a dose-response study. 186 48

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

To determine whether pharmacological control of blood pressure could affect the renal function and its deterioration in SHR with renal ablation, we studied effects of oral administration of captopril (50 mg/kg/day) and ramipril (10 mg/kg/day), angiotensin converting enzyme inhibitors (ACEI), nilvadipine (10 mg/kg/day) and benidipine (3-6 mg/kg/day), calcium channel blockers (CCB), and indapamide (10 mg/kg/day), a non-thiazide diuretic, for 2 and 12 weeks on systolic blood pressure (SBP), blood urea nitrogen (BUN) and serum creatinine (Scr), endogenous creatinine clearance (Ccr), and urinary protein excretion (UP) in SHR subjected to 5/6 nephrectomy a week before. Three weeks after the surgery, SBP (mmHg) in the untreated group was 253 +/- 8.9 (n = 11), captopril group 156 +/- 8.9 (n = 7, p less than 0.05), ramipril group 176 +/- 12 (n = 7, p less than 0.05), nilvadipine group 146 +/- 8.8 (n = 7, p less than 0.05), and benidipine group 197 +/- 8.5 (n = 7, p less than 0.05). Monotherapy with indapamide (206 +/- 4.8, n = 7, p less than 0.05) induced only a slight decrease in the SBP. Thirteen weeks after the surgery, SBP in the untreated group was 270 +/- 6.9 (n = 14), in the captopril group 191 +/- 4.8 (n = 7, p less than 0.05), in the ramipril group 160 +/- 9.5 (n = 7, p less than 0.05), in the nilvadipine group 177 +/- 13.2 (n = 7, p less than 0.05), and in the benidipine group 150 +/- 4.9 (n = 7, p less than 0.05). BUN was lower in the captopril and nilvadipine groups but not in the other treatment groups compared with the untreated group. Scr was lower in the ACEI groups. Ccr was higher in the ACEI and benidipine groups. UP was lower in all treatment groups. These results indicate that the similar reduction of SBP by ACEI and CCB has the potential to preserve renal function and to lessen renal damage in this model. Furthermore, they also suggest that ACEI have the potential to ameliorate renal function in this model. However, it remains to be determined why, despite the similar effects on SBP, deterioration of renal function in this model was prevented only by treatment with the ACEI, but not with the CCB.
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PMID:[Effects of antihypertensive therapy on the renal function in spontaneously hypertensive rats (SHR) with renal ablation]. 234 72

To determine whether pharmacological control of blood pressure could affect the renal function and levels of atrial natriuretic polypeptide (ANP) in spontaneously hypertensive rats (SHR) with renal ablation, and to ascertain the benefits of antihypertensive drugs, we studied effects of oral administration of captopril (50 mg/kg/day), an inhibitor of angiotensin converting enzyme, benidipine (3 mg/kg/day) and nilvadipine (10 mg/kg/day), newly developed blockers of calcium channel, and indapamide (10 mg/kg/day) for 14 days on systolic blood pressure, serum creatinine, blood urea nitrogen, and plasma ANP concentration in SHR subjected to surgical removal of the left kidney and infarction of two-thirds of the right kidney (5/6 nephrectomy) a week before. Three weeks after the surgery, systolic blood pressure (mmHg) in the untreated group was 253 +/- 9 (n = 10), in the captopril group 156 +/- 9 (n = 7, p less than 0.05), in the benidipine group 197 +/- 9 (n = 7, p less than 0.05), in the nilvadipine group 146 +/- 9 (n = 7, p less than 0.05) and in the indapamide group 206 +/- 5 (n = 7, p less than 0.05). Serum creatinine (mg/100 ml) was lower in the captopril group (0.58 +/- 0.02, n = 7, p less than 0.05) and in the benidipine group (0.50 +/- 0.03, n = 7, p less than 0.05) but not in the nilvadipine group and in the indapamide group 3 weeks after 5/6 nephrectomy compared to the untreated group. Blood urea nitrogen was also lower in the captopril group and in the benidipine group but not in the nilvadipine group and in the indapamide group. Plasma ANP concentration was significantly reduced by the treatment with captopril and benidipine but not with nilvadipine and indapamide. These results suggest that the reduction of blood pressure by the inhibition of angiotensin converting enzyme with captopril has the potential to ameliorate renal function of the SHR with remnant kidney, a model of chronic renal failure with hypertension, associated with the decreased concentration of plasma ANP. However, it remains to be determined whether the reduction of blood pressure by calcium channel blockers may be involved in the delayed progression of renal failure in this model since there were disparate effects on renal function and plasma ANP concentration with these two calcium channel blockers.
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PMID:Effects of antihypertensive drugs on renal function and atrial natriuretic polypeptide in spontaneously hypertensive rats with renal ablation. 252 46


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