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)

Utilization of highly enriched preparations of steroidogenic Leydig cells have proven invaluable for studying the direct effects of various hormones and agents on Leydig cell function in vitro. However, recent work indicates that isolated Leydig cells are often subjected to oxygen (O2) toxicity when cultured at ambient (19%) oxygen concentrations. Because intracellular antioxidants play an important role in protecting cells against oxygen toxicity, we have investigated the intracellular antioxidant defense system of isolated Leydig cells. The cellular levels of several antioxidants including catalase, glucose-6-phosphate dehydrogenase (G-6-PDH), superoxide dismutase (SOD) of the Cu/Zn & Mn variety, glutathione peroxidase, glutathione reductase and total glutathione were quantitated using enriched populations of Leydig cells isolated from adult male guinea pig testes. Compared to whole testicular homogenates, Leydig cells contained significantly (P < 0.01) less G-6-PDH, total SOD, glutathione reductase and total glutathione, but significantly (P < 0.001) more glutathione peroxidase. Compared to hepatic values previously reported in the guinea pig, Leydig cells contain nearly 400 times less catalase, about 14 times less glutathione peroxidase and almost 11 times less glutathione reductase. Since G-6-PDH and glutathione reductase are both necessary to regenerate reduced glutathione (GSH) which couples with glutathione peroxidase to breakdown hydrogen peroxide (H2O2) under normal conditions, it is plausible that the oxygen toxicity observed in isolated Leydig cells is due to the intracellular accumulation of H2O2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The antioxidant defense system of isolated guinea pig Leydig cells. 810 85

Mortality of patients with congestive heart failure (CHF) is high; > 40% of deaths are sudden, most often due to sustained ventricular arrhythmias (VA). In such patients frequent ventricular premature beats (VPB) and non sustained ventricular tachycardia (NSVT) are common. The relationship between VA and an increased risk for sudden death has been reported for patients with recent myocardial infarction. Although such relationship is uncertain for patients affected by dilated cardiomyopathy, many authors have reported an association between the frequency and the complexity of VA and the risk of sudden death. Many factors are responsible for VA in CHF: structural abnormalities, electrolyte imbalance, hemodynamic impairment, pharmacologic therapy and abnormal activation of neurohormonal system. ACE inhibitors have reduced VA in several experimental models, suggesting that these drugs decrease heart vulnerability to arrhythmogenic stimuli such as reperfusion and electrical stimulation. Many clinical trials have demonstrated that ACE inhibitors decreased VPB frequency and the prevalence of NSVT. Although ACE inhibitors decrease VA frequency, the reduction in cardiac mortality observed in CONSENSUS31 and in SOLVD32 trials was due only to a decrease in the progression of CHF. Recently the results of V-HeFT II33 trial have shown that the reduction in VA prevalence observed in patients treated with enalapril paralleled a reduction of sudden death. Factors that may contribute to the reduction in VA by ACE inhibitors include: increase in serum potassium; unloading of the ventricle; decrease in myocardial oxygen consumption. However, the most important factor seems related to their interference on neurohormonal system whose abnormal activation is the main mechanism of CHF progression.
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PMID:[Heart failure and arrhythmias: the role of ACE inhibitors]. 811 14

Epidemiological and clinical studies carried out over the past 30 years have unequivocally shown that cardiac hypertrophy is frequently associated with high blood pressure values adversely affecting, from a pathophysiological and prognostic view point, the clinical evolution of the hypertensive disease. From a pathophysiological view point, it has been reported that a pathologic increase in cardiac wall thickness not only impairs diastolic function, coronary circulation and reflex control of circulation exerted by cardiopulmonary volume receptors, but also enhances cardiac work and myocardial oxygen consumption. From a clinical view point, cardiac hypertrophy has been shown to increase the risk of occurrence of cardiac arrhythmias, myocardial infarction, heart failure and sudden cardiac death. Antihypertensive drugs, such as ACE-inhibitors, calcium antagonists and alpha and beta-blocking agents, by reducing high blood pressure values and concomitantly by favouring the regression of the echo- and electrocardiographic signs of cardiac hypertrophy, have been shown to physiologically restore normal cardiac function and reflex homeostatic cardiovascular control.
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PMID:[Hypertension, left ventricular hypertrophy and heart failure]. 811 22

In patients with chronic heart failure, exercise capacity and clinical symptoms correlate poorly, if at all with the degree of left ventricular dysfunction. These observations might indicate that peripheral alterations (e.g. reduced perfusion of the exercising muscle) contribute to the functional state and exercise capacity of patients with chronic heart failure. Acute improvements in hemodynamics by means of therapy with vasodilators or positive inotropes, however, could not be translated into an enhanced oxygen consumption. These studies have prompted the hypothesis that in the setting of heart failure, intrinsic abnormalities of the exercising muscle develop that prevent acute improvement in peak VO2. Indeed, ultrastructural analysis of a large cohort of patients with chronic heart failure revealed that volume density of mitochondria and surface density of mitochondrial cristae (both are parameters for the oxidative capacity of skeletal muscle) were reduced by more than 20% as compared to healthy control subjects. In contrast to left ventricular contractility parameters, ultrastructural changes of the skeletal muscle correlated closely with peak oxygen consumption, indicating that abnormalities of the exercising muscle contribute to a decreased exercise capacity in this patient group. Chronic but not acute treatment with angiotensin converting enzyme (ACE) inhibitors increases blood flow to the exercising muscle and improves peak oxygen consumption. These protracted effects of ACE-inhibitors might be due to an inhibitory effect on the vascular renin angiotensin system leading to a beneficial remodelling of the vessel wall. Forearm vessels of patients with heart failure do not respond adequately to acetylcholine and reactive hyperemia, indicating an impaired endothelial function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Are alterations of skeletal muscle ultrastructure in patients with heart failure reversible under treatment with ACE-inhibitors? 812 19

Left ventricular damage by necrosis of myocardial tissue can lead to compromise of left ventricular function, to left ventricular volume increase and ultimately to development of heart failure. This sequence in the pathophysiology has been shown to be blunted by ACE inhibitors. Volume increase, however, can also be helpful in restoring stroke volume and ameliorate elevation of filling pressures. Furthermore, very early institution of ACE inhibition has failed to improve short-term mortality after myocardial infarction in one large trial. The aim of the ECCE trial therefore is, to investigate the early effects of the ACE inhibitor captopril on compromise of exercise capacity, thought to be a first measurable sign of developing heart failure. The ECCE trial is a randomized, seven-center investigation, studying the effects of ACE inhibition on oxygen uptake in a double blind, placebo controlled design in a group of 204 patients. Sample size was calculated on the basis of a pilot trial. The study design and first not unblinded data of 104 patients are presented. The population consists of predominantly male patients with mostly first myocardial infarction. They were admitted to hospital within five hours of onset of chest pain. End-diastolic volumes were normal, but ejection fraction was moderately compromised. ACE inhibition was started after the first day, but within 72 hours of onset of chest pain. After four and after twelve weeks, oxygen uptake was considerably below expected values and one third of the patients had severe compromise of exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experiences with ACE inhibitors early after acute myocardial infarction. Rationale and design of the German Multicenter Study on the Effects of Captopril on Cardiopulmonary Exercise parameters post myocardial infarction (ECCE). 812 22

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

Enhanced formation of radicals during post-ischemic reperfusion, foremost of superoxide (O2-) and hydroxyl (OH) radicals, has been directly and indirectly demonstrated in a number of tissues. However, the close chemical interrelationship of O2- and OH with other non-radical oxidants, such as hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), makes it prudent to speak of reactive oxygen metabolites in conjunction with cell and organ dysfunction incurred by reperfusion. In the case of the heart, evidence for the causal involvement of such reactive molecular species includes (1) the increased formation of lipid peroxides, (2) the ability to mimic all facets of reperfusion injury (arrhythmias, contractile and vascular dysfunction, infarct extension) by exogenously applying reactive oxygen species, and (3) the propensity of a great variety of antioxidative and radical scavenging measures to afford cardioprotection during reperfusion. Potential sources of reactive oxygen metabolites in the reperfused heart are the mitochondrial redox-chain, endothelial enzymes such as cyclooxygenase, monoaminooxidase, NO-synthase and xanthine oxidase, and formed blood constituents (platelets, monocytes, granulocytes). According to our own results, adenosine, endogenously formed in the heart during ischemia, rapidly enhances adhesion of granulocytes introduced into the coronary system at reperfusion. Furthermore, small numbers of these cells suffice to induce contractile dysfunction in an isolated guinea pig heart model of ischemia-reperfusion injury, the major mediator of damage being HOCl. The striking disparity between the enormous volume of experimental data supporting involvement of reactive oxygen metabolites in reperfusion damage and the virtual lack of clinical-therapeutic regimens employing anti-oxidative measures is largely due to a still rudimentary knowledge of the homeostatic control of formation and removal of radicals and oxidants. In particular, the inability to correctly assess the individual time-course and extent of oxidative stress seems to be a major problem. Also, confounding issues such as compartmentation of radical formation as opposed to radical scavenging and the unwitting down-regulation of endogenous protective systems (e.g., of uric acid in the course of inhibiting xanthine oxidase) need to be resolved. On the other hand, we have been able to demonstrate protection by ACE inhibitors elicited via endothelially produced nitric oxide (a scavenger of O2- and OH) in the isolated heart. Thus, enhancement of endogenous protection may offer a perspective for mitigating against reperfusion damage.
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PMID:[Possible significance of free oxygen radicals for reperfusion injury]. 815 62

The authors have compared the ability of two non-SH-containing angiotensin converting enzyme (ACE) inhibitors (enalaprilat and lisinopril) with an -SH containing ACE inhibitor (captopril) to scavenge the hydroxyl radical (.OH). All three compounds were able to scavenge .OH radicals generated in free solution at approximately diffusion-controlled rates (10(10) M-1 s-1) as established by the deoxyribose assay in the presence of EDTA. The compounds also inhibited deoxyribose degradation in reaction mixtures which did not contain EDTA but not so effectively. This later findings also suggests that they have some degree of metal-binding capability. Chemiluminescence assays of oxidation of hypoxanthine by xanthine oxidase in the presence of luminol, confirm that the three ACE inhibitors are oxygen free radical scavengers. Our results indicate that the presence of a sulphydryl group in the chemical structure of ACE inhibitors is not relevant for their oxygen free radical scavenging ability.
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PMID:Angiotensin converting enzyme inhibitors as oxygen free radical scavengers. 824 86

The levels of angiotensin I, II (ATI, II) and angiotensin converting enzyme (ACE) were measured in 28 patients with hypoxic pulmonary hypertension and 23 normal individuals. The effects of captopril were observed in 8 of 28 patients. The results showed that the average level of ATII in the patients was significantly higher than that in normal control (P < 0.05), but the average level of ACE in the patients was significantly lower than that in the controls (P < 0.05). In 8 patients, after the use of captopril, an ACE inhibitor, for two weeks, the levels of ATII, ACE and mean pulmonary arterial pressure (mPAP) were markedly decreased (P < 0.05). But the other 20 patients treated with antibiotics, antiasthmatics, diuretics and oxygen therapy for two weeks did not show any alterations in the levels of ATII, ACE and mPAP.
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PMID:[The changes in the levels of angiotensins and angiotensin converting enzyme and effects of captopril in patients with hypoxic pulmonary hypertension]. 824 12

Infarct expansion (IE) and ventricular remodelling (VR) are interdependent pathophysiologic processes in the heart following acute myocardial infarction (AMI), and may contribute to dilatation of the left ventricle, heart failure, left ventricular aneurysm and/or rupture, and poor prognosis. IE and VR are demonstrated by echocardiography, and are usually seen with large, transmural, anterior AMI, hypertension and persisting occlusion of the infarct-related coronary artery. All myocardial tissue components are involved in IE and VR, and local generation of growth factors, vasoactive mediators, oxygen-derived free radicals, and activation of the renin-aldosterone-angiotensin system may have pathophysiological significance. These mechanisms can provide the opportunity for therapy, and evidence suggests that treatment with angiotensin converting enzyme-inhibitors can attenuate IE and VR.
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PMID:[Infarction expansion and ventricular remodelling after acute myocardial infarction]. 825 36


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