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

Acute and 1-month toxicity studies with SCH 31846, a nonsulfhydryl anti-hypertensive agent which acts by inhibiting angiotensin-converting enzyme, were initiated to evaluate its toxicity. The oral LD50s in mice and rats were approximately 1.8 and 2.5 g/kg, respectively, while the iv LD50 was approximately 450 mg/kg in mice and 150 mg/kg in rats. Signs of acute toxicity in rats and mice included salivation, hypoactivity, ataxia, prostration, and convulsions. In a 1-month dog study at oral doses of 25, 75, or 150 mg/kg, there was a dose-related increase in emesis between 1 and 2 hr after dosing. Absorption studies showed peak blood concentrations occurring in dogs between 0.3 and 1 hr after dosing. No other noteworthy antemortem changes were observed. In a 1-month rat study at oral doses of 30, 180, or 600 mg/kg, the hematocrit and hemoglobin values of the 600 mg/kg-dosed female rats were slightly but significantly (p less than 0.05) decreased and the blood urea nitrogen was slightly but significantly (p less than 0.05) increased in all SCH 31846-dosed male rats and the 600 mg/kg-dosed female rats. Absorption studies in male rats at doses of 30, 180, and 600 mg/kg indicate that SCH 31846 is well absorbed in rats. The 150 mg/kg-dosed dogs and the 180- and 600 mg/kg-dosed rats had a slight increase in the number of renin-containing granules in the renal juxtaglomerular cells. No other compound-related microscopic changes were observed. These data are similar to data reported for Captopril and suggest that in the dog and rat the toxicity of ACE inhibitors is not dependent upon the presence or absence of a sulfhydryl group.
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PMID:Acute and subchronic toxicity of a nonsulfhydryl angiotensin-converting enzyme inhibitor. 300 64

Although serum angiotensin converting enzyme (EC 3.4.15.1) activity has generally been shown to be increased in patients with sarcoidosis, considerable variation in the diagnostic usefulness of this test has been reported. We investigated the possibility that this variation may be the result of inhibition of the widely used spectrophotometric assay by various substances. We also prospectively examined the predictive value of measurements of this enzyme in serum from 100 patients being evaluated for sarcoidosis. The following did not significantly affect the results: storage at 4 or 25 degrees C for one week, hemoglobin, lipoproteins, or corticosteroid medications. Bilirubin, at concentrations of 20 mg/L of serum or move, significantly inhibited the assay. Sera with increased activity showed nonlinear reaction rates during the usual 60-min reaction interval, This was corrected by shortening the reaction time to 30 min. We found a predictive value of 88% when the serum angiotensin converting enzyme test was applied to the diagnosis of active sarcoidosis.
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PMID:Characterization of a spectrophotometric assay for angiotensin converting enzyme. 625 24

Thirty four beagle dogs, male and female were orally given 10, 30, 100 and 200 mg/kg/day of captopril, an angiotensin converting enzyme inhibitor, for 3 months followed by a recovery test for 4 weeks. One of 4 female dogs which were treated with the highest dose of 200 mg/kg/day throughout the experimental period died of bronchial pneumonia. Hypersalivation and occasionally vomiting was observed in dogs treated with 100 and 200 mg/kg/day. Skin eruption such as erythema and papules was observed mostly at the ventral surface of the neck, chest and upper abdomen in dogs in these two experimental groups. Histological examination of the lesion revealed cellular infiltration with edema and expansion in the dermis and slight hyperkeratosis with parakeratosis and acanthosis. Changes in erythrocyte counts, hematocrit values and hemoglobin contents during the course of administration were variable among dogs but these were obvious in animals treated with higher doses. An increase in erythropoiesis of the bone marrow, extramedullary hematopoiesis and slight hemosiderosis in liver and spleen were revealed by histological examination. Above histological observations suggest that captopril may cause hemolysis. Hypertrophy and hyperplasia of juxtaglomerular cells with increased number of JG granules were shown in the highest dosage group even 4 weeks after suspension of captopril administration. A distinct plasma renin activity supported the morphological changes. From the results of three months administration of captopril to beagle dogs, the maximum non-toxic dose may be around 10 mg/kg/day and toxic dose 100 mg/kg/day.
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PMID:[Three month subacute toxicity of captopril in beagle dogs]. 627 85

Cathepsin B was purified about 11,000-fold from monkey skeletal muscle by ammonium sulfate fractionation and sequential column chromatographies monitored by assaying of Z-Phe-Arg-MCA hydrolase activity. The purified enzyme gave a single protein band on SDS-polyacrylamide gel electrophoresis, and its molecular weight was estimated to be 24,000 by gel filtration. It had a pH optimum of 6.5, required a thiol reducing agent for activation, and was inhibited by various thiol protease inhibitors. These properties were similar to those reported for cathepsins B from other sources. Although the enzyme scarcely hydrolyzed ordinary proteins, such as casein, hemoglobin, and bovine serum albumin, it degraded myosin and actin among various myofibrillar proteins. These results strongly suggested that skeletal muscle cathepsin B may participate in the degradation of muscle proteins in vivo. In addition, cathepsin B was shown to hydrolyze various neuropeptides such as Leu-enkephalin, beta-neoendorphin, alpha-neoendorphin, dynorphin(1-13), and substance P. It appeared to act on these peptides mainly as a dipeptidyl carboxypeptidase, although not so rigorously, presumably due to its endopeptidase activity.
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PMID:Purification and characterization of cathepsin B from monkey skeletal muscle. 672 39

The respective effects of 6 month's administration of beta-blockers (atenolol, metoprolol, carteolol and arotinolol), calcium-channel blockers (nicardipine, diltiazem) and angiotensin converting enzyme inhibitor (enalapril) on hemoglobin A1c (HbA1c) levels were evaluated in hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM), using a retrospective method. NIDDM patients with stable HbA1c and body weight were selected for this study. The following results were obtained. (1) The administration of nicardipine or beta-blockers significantly elevated HbA1c levels. (2) The administration of diltiazem or enalapril did not have any influence on HbA1c levels. These findings suggest that not only beta-blocker but nicardipine (dihydropyridine type calcium-channel blocker) may cause deterioration in glucose metabolism in NIDDM patients.
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PMID:Nicardipine may impair glucose metabolism in hypertensive diabetic patients. 753 75

Erythrocytosis is infrequently seen in renal transplant recipients. Both theophylline and angiotensin converting enzyme (ACE) inhibitors have been reported to decrease the elevated hematocrit (Hct) and hemoglobin (Hgb) levels. We studied the efficacy of the ACE inhibitors ramipril (n = 6) and enalapril (n = 1) in seven stable renal transplant recipients. Although the ACE inhibitors significantly reduced the elevated Hct and Hgb levels during the short and long term (Hct 53 +/- 1 vs 48.8 +/- 0.7%; Hgb 17.8 +/- 0.4 vs 16.7 +/- 0.3 vs 16.7 +/- 0.3 gm/dl, at 1 year), the clinical significance of these reductions remains unknown. During therapy there were no significant changes in the blood pressure, serum creatinine and potassium levels and the medications were well tolerated.
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PMID:Long term effects of ACE inhibitors on the erythrocytosis in renal transplant recipients. 760 51

Patients with diabetes mellitus are more frequently hypertensive than age-matched non-diabetic subjects. They are confronted with a markedly increased risk of coronary vascular disease, of progressive nephropathy and renal end-stage diseases. The most common type of hypertension in type I and type II diabetics is essential hypertension, probably as a consequence of insulin resistance and hyperinsulinemia. Hyperglycemia and hypertension are both significantly involved in the progression of diabetic nephropathy. Hence, the modern therapeutic concept consists of optimal blood glucose control and strict blood pressure control. Progression of the nephropathy may be halted in most of the cases by adhering to set limits in mean arterial blood pressure, glycated hemoglobin and urinary albumin excretion rate. Furthermore, a significant decrease in cardiovascular mortality may be achieved. In case the blood pressure targets cannot be met by non-drug therapies and life-style modifications, antihypertensive drug therapy has to be initiated. The selection of antihypertensives should be based on the concomitant diabetes mellitus with its additional cardiovascular risk factors hyperlipidemia and hyperinsulinemia. In general, preference should be given to so-called metabolic neutral substances such as ACE inhibitors or calcium antagonists or to alpha-blockers which may have positive metabolic effects. Meanwhile, data from several prospective studies claim that ACE inhibitors and calcium antagonists exert nephroprotective effects beyond their beneficial blood pressure lowering effects, thereby preventing the progression of diabetic nephropathy. However, these drugs should not be uncritically used and we should be aware of their potential adverse effects. The differential therapy of hypertension in diabetes mellitus requires mature consideration before initiation of therapy, an individualized concept of therapy, and careful monitoring during treatment.
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PMID:[Hypertension, microalbuminuria and insulin resistance in diabetes mellitus]. 784 97

The inhibitory effect on angiotensin converting enzyme (ACE) activity by hemorphins isolated from an enzymatic bovine hemoglobin hydrolysate was reported. Inhibitory kinetics proved that inhibition mechanism was non-competitive. The stability of hemorphins towards ACE was studied.
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PMID:Inhibition and inhibition kinetics of angiotensin converting enzyme activity by hemorphins, isolated from a peptic bovine hemoglobin hydrolysate. 794 62

Changes in superoxide dismutase (SOD), catalase (C), and peroxidase (P) blood activity, as well as the activity of glucose-6-phosphate dehydrogenase (G-6-PDH), isocitrate dehydrogenase (ICDH), malate dehydrogenase (MDH), and peroxide resistance of erythrocytes (PRE) have been studied in 45 gastroenterologic patients under different types of general anesthesia. A significant increase in G-6-PDH, SOD, K, P activity and an increase in ICDH and MDH activity, as well as a drop in PRE which tends to return to baseline postoperatively have been established during general anesthesia. SOD expressed the greatest intergroup differences. A fragment of mechanism of energy transfer in the erythrocyte aimed at hemoglobin oxygenation and tissue hypoxia compensation has been suggested.
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PMID:[Effects of general anesthesia on the regulation of hydrogen peroxide metabolism in erythrocytes]. 801 May 17

Twenty-nine patients with unilateral renal artery stenosis or occlusion were investigated. The veno-arterial gradient (VA-gradient) of erythropoietin (EPO), haemoglobin oxygen saturation and plasma renin activity (PRA) was determined separately in each kidney before and 1 h after angiotensin converting enzyme inhibition (ACE-inhibition). The VA-gradient of EPO and of hemoglobin oxygen saturation were the same in the affected and unaffected kidney during basal conditions. During ACE-inhibition the VA-gradient of EPO disappeared on the affected side but not on the unaffected side. A fall in s-EPO after ACE inhibition was demonstrated in the renal vein on the affected side (-1.4 U l-1, p < 0.01), in the contralateral vein (-0.8 U l-1, p < 0.01) and in the aorta (-0.6 U l-1, p < 0.01). The O2-gradients were reduced on both sides after captopril, from 10.8-7.5% (p < 0.04) on the affected side and from 10.8-9.0% (p < 0.04) on the contralateral. It is suggested that the stimulated renin-angiotensin system may be important for EPO production in the affected kidney in unilateral renal disease.
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PMID:Effect of captopril on the renal veno-arterial gradient of erythropoietin and oxygen in unilateral renal artery disease. 814 Mar 97


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