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)

Rats were injected with various amounts of bovine albumin (0.5, 1.0 and 1.75 g/24h), inducing thereby proteinuria ranging from 100 to 400 mg/24h. The glomerular oxygen uptake, dry weight and glucose-6-phosphate dehydrogenase (G-6-PHD) activity were measured on the 4th day of proteinuria and in a group of control animals. Oxygen uptake increased of +60%, expressed per glomerulus and of +25% when expressed per milligram dry weight and this increase was not different between the 3 groups of rats. Glomerular dry weight increased significantly in the 3 series. There was an highly significant relationship between glomerular dry weight and oxygen uptake, combining the 3 series together. G-6-PDH increased as expected from previous experiments and this increase was more marked for the more marked proteinuria. The relationship between G-6-PDH and QO2 was of borderline statistical significance (p=0.05). The glomerular hypertrophy, oxidative hyperactivity and increase in G-6-PDH activity are probably related to transcellular transport of protein.
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PMID:Glomerular metabolism in protein-load proteinuria. 91 75

All-trans retinoic acid and its derivative retinoid, two new compounds with expanding therapeutic spectrum in dermatology, were investigated in biochemical assays. Both substances provoke an increase in oxygen consumption of rat skin whereas in human skin only retinoid was found active in this respect. In resting yeast cells, both substances failed to exert any significant influence on oxygen consumption.--Pure G-6-PDH was inhibited by retinoic acid and retinoid in concentrations as low as 5 mug/ml. In human skin homogenates, LDH-, GAPDH-, and G-6-PDH-activities were inhibited by retinoic acid whereas GOT-, LAP-, and ALD-activites remained practically unchanged following an incubation with retinoic acid in concentrations between 1 and 100 mug/ml for 60 min.--The data collected in this study were briefly discussed with regard to the use of retinoic acid and its derivatives in psoriasis.
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PMID:Influences of retinoic acid and retinoid on skin metabolism. Investigations of oxygen consumption and enzymatic activities of human skin. 98 76

The changes of anthralin under various physical conditions (temperature, ultraviolet irradiation) were investigated by biochemical assay (inhibition of G-6-PDH activity), by oxygen monitor (increased oxygen consumption in the presence of zinc ions), and by recording the absorption spectra. Higher temperatures and exposure to ultraviolet light provoke the formation of a biochemically highly active compound within short periods of time. In clinical therapy, this compound may easily be formed when anthralin is used together with ultraviolet irradiation (Ingram method). Changes in the biochemical activity of anthralin are accompanied by changes in the absorption spectra. Oxidation (e.g. in the presence of zins ions) or inhibition of oxidation (e.g. in the presence of salicylic acid) may easily be detected by spectroscopic assay.
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PMID:Influence of ultraviolet light, various temperatures, and zinc ions on anthralin (dithranol). Biochemical and chemical investigations. 118 90

Patients with essential arterial hypertension demonstrate abnormal vasodilator capacity either during increased cardiac metabolic demand or during pharmacological vasodilation. Structural and functional damage to the coronary microcirculation has been proposed as one of the major causes of impaired coronary reserve in this disease. To assess the role of microvascular impairment in regional myocardial blood flow (MBF), 27 patients with essential hypertension were evaluated by dynamic positron emission tomography (PET) at rest, during atrial pacing and after dipyridamole infusion and compared with 13 healthy subjects. All patients had normal coronary arteries, 17 had moderate to severe hypertension and 10 had mild hypertension. Baseline mean MBF of 0.97 +/- 0.25 ml/min/g was significantly increased to 1.60 +/- 0.38 during atrial pacing and 2.35 +/- 0.95 after dipyridamole infusion (p < 0.01); however, mean flow during atrial pacing and after dipyridamole infusion was significantly lower than in healthy subjects (2.15 +/- 0.73 and 3.71 +/- 0.86 ml/min/g, p < 0.05 and p < 0.01, respectively). The MBF response to atrial pacing and dipyridamole infusion was similarly depressed in patients with mild and severe hypertension. The study was repeated after 6 months of antihypertensive treatment with the calcium antagonist verapamil or the angiotensin converting enzyme (ACE) inhibitor enalapril in a subgroup of 20 patients as part of a randomised, single-blind clinical trial. This study is still in progress; the initial 16 patients treated with verapamil or enalapril showed an obvious improvement in MBF values during atrial pacing and after dipyridamole infusion after 6 months of therapy (mean MBF: 2.10 +/- 0.64 and 2.99 +/- 1.63 ml/min/g, respectively, p < 0.05 vs pretreatment values). In conclusion, obvious impairment of MBF during atrial pacing and after dipyridamole infusion was observed in hypertensive patients with normal coronary arteries and this appeared unrelated to the severity of hypertension. Therapy with verapamil or enalapril improved coronary reserve and MBF response to an increase in myocardial oxygen demand.
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PMID:Regional myocardial blood flow and coronary reserve in hypertensive patients. The effect of therapy. 128 84

Administration of captopril, a scavenger of oxygen derived radicals as well as an inhibitor of angiotensin converting enzyme, has been an efficient way of treating diabetic proteinuria. In the present study, we evaluate whether captopril can ameliorate diabetic proteinuria as an effect on oxidative stress in streptozotocin- induced diabetic rats (STZR). At four weeks after the injection of streptozotocin (50 mg/kg, i.v.), STZR (n = 5) exhibited microalbuminuria. The rate of urinary albumin excretion was 0.5 +/- 0.1 and 2.6 +/- 0.3 mg/24hr in age-matched control rats (CR; n = 5) and STZR, respectively. Compared to CR, STZR also showed an extremely increased rate of urinary lipid peroxides (LPO) excretion, an index of oxygen derived radicals generation. The respective values for CR and STZR were 0.6 +/- 0.3 and 6.9 +/- 0.6 mumol/24 hr. Significant amelioration of urinary albumin and LPO excretion rate by the treatment of insulin (2 U/day) suggests that these are associated with the diabetic state induced by streptozotocin rather than a direct effect of streptozotocin. Chronic administration of captopril, which did not cause any discernible effect on CR, significantly reduced the urinary albumin excretion rate and decreased LPO excretion in STZR. The urinary albumin excretion rate was significantly correlated with the LPO excretion rate (p = 0.0004). These results suggest that oxidative stress can be responsible for diabetic microalbuminuria, and captopril could diminish the lipid peroxidation and ameliorate the microalbuminuria in diabetic rats.
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PMID:Amelioration of diabetic microalbuminuria and lipid peroxidation by captopril. 129 45

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

Hearts with compensatory pressure-overload hypertrophy show an increased intracardiac activation of angiotensin II that may contribute to ischemic diastolic dysfunction. We studied whether pressure-overload hypertrophy in response to aortic banding would result in exaggerated diastolic dysfunction during low-flow ischemia and whether the specific inhibition of the cardiac angiotensin converting enzyme by enalaprilat would modify systolic and diastolic function during ischemia and reperfusion in either hypertrophied or nonhypertrophied hearts. Isolated, red blood cell-perfused isovolumic nonhypertrophied and hypertrophied rat hearts were subjected to enalaprilat (2.5 x 10(-7) M final concentration) infusion during 20 minutes of baseline perfusion and during 30 minutes of low-flow ischemia and 30 minutes of reperfusion. Coronary flow per gram was similar in nonhypertrophied and hypertrophied hearts during baseline perfusion, ischemia, and reperfusion. At baseline, left ventricular developed pressure was higher in hypertrophied than nonhypertrophied hearts in untreated groups (224 +/- 8 versus 150 +/- 9 mm Hg; p less than 0.01) and in enalaprilat-treated groups (223 +/- 9 versus 145 +/- 8 mm Hg; p less than 0.01). During low-flow ischemia, left ventricular developed pressure was depressed but similar in all groups. All groups showed deterioration of diastolic function; however, left ventricular end-diastolic pressure increased to a significantly higher level in untreated hypertrophied than in nonhypertrophied hearts (65 +/- 7 versus 33 +/- 3 mm Hg; p less than 0.001). Enalaprilat had no effect in nonhypertrophied hearts, but it significantly attenuated the greater increase in left ventricular end-diastolic pressure in hypertrophied hearts treated with enalaprilat compared with no drug (65 +/- 7 versus 50 +/- 5 mm Hg; p less than 0.01). The beneficial effect could not be explained by differences in coronary blood flow per gram left ventricular weight, glycolytic flux as reported by lactate production, myocardial water content, oxygen consumption, and tissue levels of glycogen and high energy phosphate compounds. During reperfusion, all hearts showed a partial recovery of developed pressure to 70-74% of initial values. No effect of enalaprilat could be detected during reperfusion on systolic and diastolic function or restoration of tissue levels of high energy compounds. In conclusion, our experiments show that hypertrophied red blood cell-perfused hearts manifest a severe impairment of left ventricular diastolic relaxation in response to low-flow ischemia in comparison with control hearts. Further, our experiments support the hypothesis that the enhanced conversion of angiotensin I to angiotensin II in rats with pressure-overload hypertrophy contributes to the enhanced sensitivity of hypertrophied hearts to diastolic dysfunction during low-flow ischemia.
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PMID:Exacerbation of left ventricular ischemic diastolic dysfunction by pressure-overload hypertrophy. Modification by specific inhibition of cardiac angiotensin converting enzyme. 131 16

Angiotensin converting enzyme inhibitors are utilized in the treatment of essential hypertension and of chronic cardiac failure. They are also employed in the treatment of the myocardial lesion of ischemia-reperfusion, which involves oxygen free radicals. In the present study we investigated the possibility of three angiotensin converting enzyme inhibitors (captopril, enalapril, lisinopril) to act as hydroxyl radical scavengers. The rate constants for reactions of those compounds with .OH were determined using the deoxyribose method. All there compounds proved to be good scavengers of .OH with rate constants of about 10(10)M-1s-1 and are iron chelators specially enalapril. The fact that captopril possesses a thiol group does not confer an higher antioxidative capacity. These results suggest that scavenging of oxygen free radicals may be a possible mechanism contributing to the therapeutic effect of angiotensin converting enzyme inhibitors.
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PMID:[Angiotensin-converting enzyme inhibitors as neutralizers of hydroxyl radical]. 132 14

The hemodynamic effects of imidapril, a novel nonsulfhydryl angiotensin-converting enzyme inhibitor, were examined in anesthetized dogs by the intravenous injection of its active metabolite 6366A ((4S)-3-((2S)-2-[N-((1S)-1-carboxy-3- phenylpropyl)amino]propionyl)-1-methyl-2-oxoimidazolidine-4-carboxylic acid, CAS 89371-44-8) and were compared to those of enalaprilat. 6366A (1-100 micrograms/kg) reduced the blood pressure and total peripheral resistance in a dose-dependent manner, while causing no marked changes in heart rate, LV dp/dtmax, and pulmonary arterial pressure. The cardiac output and stroke volume were slightly increased. Blood flow in the common carotid artery, the vertebral artery, and the femoral artery was reduced or tended to decrease, while the superior mesenteric arterial blood flow was increased. These effects were similar to those of enalaprilat. 6366A did not inhibit the pressor response of angiotensin II, but markedly inhibited that of angiotensin I, and the effects of 6366A on regional blood flow were opposite to those of angiotensin II. Thus, 6366A appears to produce its hemodynamic effects by angiotensin converting enzyme inhibition, as does enalaprilat. 6366A also tended to decrease myocardial oxygen consumption. These results suggested that the hemodynamic effects of imidapril on the heart and on regional blood flow are similar to those of enalapril.
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PMID:Acute hemodynamic effects of the active metabolite of imidapril, (4S)-3-((2S)-2-[N-((1S)-1-carboxy-3-phenyl-propyl)amino]propionyl)-1- methyl-2-oxoimidazolidine-4-carboxylic acid, and enalaprilat in anesthetized dogs. 133 27

Pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), blood pressure (BP) were monitored before and after hypoxia, Captopril and Nitrendipine injected (7 mg/kg and 100 micrograms/kg) in group A(n = 9), and group B(n = 7) respectively results showed that during hypoxia PAP in all the pigs increased significantly (P < 0.05), compared with normoxia, and after captopril and nitrendipine intravenous injection, the PAP dropped significantly (from 3.76 +/- 0.25 to 3.43 +/- 0.1 kPa versus from 4.21 +/- 0.19 to 3.18 +/- 0.17 kPa. ACE in captopril group was significant reduced P < 0.05 (58.4 +/- to 27.0 +/- 3.0 mumol.min-1/L), but in nitrendipine group was not markedly changed (P > 0.05), we found that reducing the degree of PAP and its duration time, lowered the pulmonary vascular resistance (PVR) and right ventricle stroke index (RVSWI), also improved capacity of oxygen delivery. Nitrendipine was better than captopril, maybe it is an useful drug for patients with pulmonary hypertension.
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PMID:[Comparative studies between the effects of captopril and nitrendipine on the hemodynamics and angiotensin converting enzyme of pigs with acute hypoxic pulmonary hypertension]. 133 19


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