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)

Chronic heart failure (CHF) is present in 1-10% of the whole population. From the drugs used in CHF so far only angiotensin converting enzyme inhibitors and nitrate with hydralazine improved the survival which was caused by beneficial influence of these drugs on neurohormonal factors. There is growing interest in beta-blockers which are believed to stop the progress of CHF. Although the first attempts of using beta-blockers in the treatment of CHF took place in 70-ties, only recent years brought better understanding of mechanisms of their action. The beneficial effect of beta-blockers in CHF is related to their protective influence on myocardium and to hampering of apoptosis--programmed cell death--the phenomenon which is exaggerated in CHF. The investigations carried out in last years proved that carvedilol which is beta 1-, beta 2- and alpha 1-blocker and has antioxidant properties improved clinical status and reduced mortality in the cohorts of patients with all-cause CHF. At present great trials estimating various beta-blockers and comparing these drug among themselves are being conducted.
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PMID:[Use of beta-adrenoreceptor antagonists in treatment of patients with chronic heart failure]. 955 9

Among cardiovascular diseases, hypertension, angina pectoris, acute myocardial infarction and ischemic stroke present a circadian pattern with a greater incidence of unfavourable events between awakening and noon. Chronotherapy aims to use drugs that release their active principles at different times during the day, according to biological needs. In chronotherapy of cardiovascular diseases, a particular attention has been paid to slow-release drugs that assure a 24 hours therapeutic effect with once a day administration. In primary hypertension well controlled by monotherapy (dipper hypertensives), the morning administration of long-acting beta-blockers and calcium antagonists has shown to control blood pressure over 24 hours, whereas ACE-inhibitors have proved more effective when administered at evening. In secondary hypertension (non dipper hypertensives) the administration of calcium antagonists is more effective at evening. Patients with severe hypertension need polytherapy. In that case, at least one of the antihypertensive drugs should be given at evening to lower night blood pressure values, which are particularly elevated also during sleep, and so to prevent an excessive blood pressure rise on awakening. In chronic monotherapy of ischemic heart disease, long-acting beta-blockers and calcium antagonists have shown to be equally effective when they are administered at morning, whereas slow-release nitrates, which need a nitrate-free interval, are to be administered either at morning or at evening, according to the expected time of onset of anginal pain. ASA seems to reduce the morning incidence of acute myocardial infarction, while tissue-type plasminogen activator presents a circadian variation of its thrombolytic activity with a higher efficacy between noon and midnight.
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PMID:[Application of chronotherapy to cardiovascular diseases]. 979 79

The management of cardiac failure due to diastolic dysfunction is not well codified and is often empirical. It has three objectives: improving the physiopathological components of ventricular filling, treating the associated aggravating pathological conditions, and treating the basic cause of the dysfunction. Symptomatic treatment aims to reduce venous congestion (by diuretics or nitrate derivatives), to prolong the diastolic period by slowing the heart rate (by betablockers, bradycardising calcium antagonists or digitalis in cases of irreducible atrial fibrillation), to improve passive ventricular distensibility by an effect on remodelling (by angiotensin converting enzyme inhibitors or anti-aldosterone diuretics). The treatment of associated pathological conditions is particularly important. It is essential to maintain or reestablish an effective atrial systole by cardioversion and anti-arrhythmic drugs in atrial fibrillation, by dual chamber pacing in cases of atrioventricular asynchrony due to atrioventricular block. Treatment of the underlying cause aims to induce regression of ventricular hypertrophy of hypertensive origin by using antihypertensive drugs with this property. In coronary artery disease, the choice is determined by the clinical context because nearly all anti-anginal or interventional treatments may improve ischaemic diastolic dysfunction. The same applies in hypertrophic cardiomyopathy because most types of treatment (betablockers, verapamil, cardiac pacing, surgery) may improve diastolic function. Finally, in valvular aortic stenosis, aortic valve replacement restores normal diastolic function.
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PMID:[Diastolic cardiac failure: therapeutic modalities]. 986 5

Since angiotensin-converting enzyme (ACE) produces angiotensin II in the heart, ACE inhibitors may prevent coronary vasoconstriction and increase coronary blood flow. On the other hand, since ACE inhibitors also inhibit kininase II which results in reduced degradation of bradykinin, ACE inhibitors may increase cardiac nitric oxide (NO) levels via stimulation of bradykinin receptors. This study was undertaken to test whether ACE inhibitors increase the cardiac NO levels and coronary blood flow in the ischemic myocardium. In 34 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery. When either imidaprilat or cilazaprilat of 3 microg/kg/min was infused into the bypass tube for 10 min after reduction of coronary blood flow due to partial occlusion of the bypass tube, coronary blood flow increased from 31 +/- 1 to either 45 +/- 5 or 43 +/- 4 ml/100 g/min despite no changes in coronary perfusion pressure (43 +/- 2 mmHg). During an infusion of either imidaprilat or cilazaprilat, bradykinin and the end-products of NO (nitrate + nitrite) concentrations of coronary venous blood were markedly increased, which were attenuated by either HOE-140 (an inhibitor of bradykinin receptors) or by N(omega)-nitro-L-arginine methyl ester (an inhibitor of NO synthase). We also observed increases in cardiac bradykinin and NO levels due to either imidaprilat or cilazaprilat in the low constant coronary blood flow condition. It is concluded that ACE inhibitors can increase cardiac NO levels via the accumulation of bradykinin in the ischemic myocardium.
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PMID:Inhibition of angiotensin-converting enzyme increases the nitric oxide levels in canine ischemic myocardium. 992 80

Little published information regarding current pharmacotherapeutic treatment patterns for congestive heart failure (CHF) in nonacademic, ambulatory care settings is available. We sought to assess, in a nonacademic primary care environment, pharmacotherapeutic treatment patterns for CHF with respect to consistency with clinical trial evidence and published treatment guideline recommendations. Over an 18-month period, we examined CHF pharmacotherapy using a computerized, integrated clinical diagnoses and prescription database from an outpatient community healthcare center without academic affiliations. We identified adult patients meeting contact criteria and with diagnosis of CHF by International Classification of Diseases (ICD-9-CM) coding and assessed prescribed therapy as well as select comorbid conditions. Drugs of interest included those with known or suspected benefit or detriment and those with unproven benefit. An eligible group of 14,983 patients was identified, from which a cohort of 148 patients with CHF was selected. Forty-one percent of these 148 patients were prescribed an angiotensin converting enzyme (ACE) inhibitor, 34% digoxin, 12% diuretic, 12% hydralazine + nitrate, 20% inhaled beta-agonists, and 66% warfarin. Only 5% of patients were prescribed the combination of an ACE inhibitor, digoxin, and diuretic. Thirty-one percent had a comorbid diagnosis of atrial fibrillation, of whom 44% were prescribed digoxin, 22% diltiazem, 15% beta-blockers, 15% digoxin and diltiazem, 7% digoxin and a beta-blocker, and 33% warfarin. In general, recommended therapies for CHF appeared underutilized in this cohort, whereas those of unclear benefit and potential detriment appeared overutilized. Although these results may not be readily generalized to the entire healthcare system, they do suggest a need for additional analysis and potential intervention.
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PMID:Treatment patterns for heart failure in a primary care environment. 1017 71

Vasodilator therapy with nitrates has been used for almost a century to bring relief to patients suffering from angina. The acute anti-ischemic effects of nitro-vasodilators for the treatment and prevention of anginal attacks is unquestioned. In addition, nitrates are administered in order to reduce symptomatic and silent ischemic episodes, in patients with proven coronary heart disease who exert ST segment alterations on Holter monitoring. The reduction in total ischemic burden may result in an improved prognosis with regard to infarct prevention and possible prevention of deterioration of left ventricular function due to repetitive episodes of myocardial ischemia. In patients with unstable angina, administration of nitrates significantly diminishes ischemic episodes and reduces the number of clinically symptomatic anginal attacks. The prevention of left ventricular dilatation in patients within the first few days and months following acute myocardial infarction may be due to the reduced preload. In patients with heart failure, preload reduction with nitrates and afterload reduction with hydralazine was tested versus angiotensin converting enzyme (ACE) inhibitors. However, unfortunately, very few data are available concerning the combination therapy of ACE inhibitors and nitrates in heart failure and following acute myocardial infarction. Long-term continuous administration of high doses of nitrates may cause nitrate tolerance, thus reducing the vasodilator potency of these drugs. Since nitrates were introduced into medical therapy many decades before randomized controlled trials were performed, and evidence-based medicine became the basic principal for medical therapy, there are still indications and situations where the full therapeutic potential of nitrates is not being fully appreciated. During recent decades, other anti-ischemic drugs, i.e., beta-receptor agonists and calcium channel blockers, were introduced into the clinical setting and contributed to an optimized therapy for patients with coronary heart disease. Nevertheless, due to their proven and unsurmounted symptomatic efficacy, nitrates will remain one of the cornerstones of acute and long-term therapy of patients with coronary heart disease far beyond the year 2000.
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PMID:Role of nitrates for the therapy of coronary artery disease patients in the years beyond 2000. 1049 56

In 1998, nitric oxide (NO) was extensively explored. First studies demonstrating a beneficial effect of inhaled NO in patients with pulmonary hypertension, right ventricular dysfunction and intractable heart failure were published. It was further shown, that, in patients with essential hypertension, impaired vasodilatation can be improved by vitamin C as an antioxidant, an effect that can be reversed by NO-synthase inhibition. Unlike arotinolol, which has no antioxidat effect, carvedilol is a beta- and alpha-blocker with antioxidative properties that may prevent the development of nitrate tolerance. In clinical cardiology, the main focus is on the prevention and therapy of coronary heart disease, heart failure and hypertension: a Task force report on the prevention of coronary heart disease in clinical practice. Proceedings on anticoagulant therapy and Guidelines for antithrombotic management were published in 1998. There is an agreement that in mild hypertension the decision how to treat should be based on the estimate of cardiovascular risk and not on an arbitrary blood pressure threshold. Diuretics and betablockers should be preferred unless they are contraindicated, or there are positive indications for other drug classes. Studies also strongly suggest that therapy with relatively small doses of two different classes of drugs is the effective way to treat the majority of patients and minimize side effects. In heart failure, the evidence for the current treatment with diuretics, ACE-inhibitors and digoxin, in selected patients, is well established.
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PMID:[Cardiology 1998]. 1051 May 45

Inhibitors of angiotensin converting enzyme (ACE) have been developed recently for therapeutic purposes in hypertension and ischemic cardiovascular diseases. Ogiku et al. reported that one such inhibitor, imidapril, significantly prolonged survival in stroke-prone spontaneously hypertensive rats (SHRSP). The present study was designed to investigate the effect of imidapril on cerebral blood vessels in SHRSP to clarify role of the ACE inhibitor in mechanisms of cerebral thrombosis and stroke. Imidapril was administered orally at 1.0 and 5.0 mg/kg/day for 3 weeks from the age of 7 weeks, and was shown to prevent the usual increase in blood pressure seen in these animals. It also delayed He-Ne laser-induced cerebral thrombosis and increased significantly the plasma concentration of nitric oxide metabolites (NO2/NO3). To confirm the association between nitric oxide (NO) and these effects of imidapril, an inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) was dissolved in drinking water and administered to the animals for 3 weeks. Four of six rats died from stroke when L-NAME was given alone. When imidapril (5.0 mg/kg/day) was administered with L-NAME, however, the animals showed no signs or symptoms of stroke. In these instances, therefore, the concurrent administration of L-NAME with imidapril reversed significantly the effects of imidapril. Intravenous injection of imidaprilat (100 microg/kg), an active metabolite of imidapril, also decreased blood pressure significantly and increased the plasma levels of NO2/NO3 after 5 min. Moreover, imidaprilat enlarged arteriolar diameters and caused an increase in red cell velocity and mean blood flow in pial arterioles after 15 min. The results strongly suggested that imidapril protects cerebral vessels in SHRSP by elevating the release of NO, thereby improving the cerebral circulation and reducing the tendency to thrombosis and stroke.
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PMID:Protective effects of imidapril on He-Ne laser-induced thrombosis in cerebral blood vessels of stroke-prone spontaneously hypertensive rats. 1082 69

Endothelial function is impaired in hypertension. In the present study the effects of long-term antihypertensive therapy on endothelial production of nitric oxide (NO) were investigated. Fifteen untreated mild to moderate essential hypertensive patients and 13 normotensive subjects were enrolled in this study. Blood pressure, heart rate, lipid profiles, cyclic guanosine 3', 5'-monophosphate (cGMP) and nitrite/nitrate (NOx), which are stable metabolites of NO, were measured. The hypertensive patients were treated with a calcium antagonist, benidipine (CAS 91559-74-5) (Ca group: n = 8) or an angiotensin converting enzyme inhibitor, trandolapril (CAS 87679-37-6) (ACEI group: n = 7) and 12 weeks after the treatment the same examinations were performed. NOx and cGMP levels in hypertensive patients were significantly lower than those in normotensive subjects (32.3 +/- 4.1 versus 49.0 +/- 6.5 mumol/l and 2.16 +/- 0.39 versus 3.39 +/- 0.42 pmol/ml, respectively). Both antihypertensive agents decreased the elevated blood pressure (mean blood pressure; 120 +/- 3 to 99 +/- 3 mmHg in Ca group and 117 +/- 4 to 104 +/- 4 mmHg in ACEI group) and normalized the decreased NOx and cGMP levels (29.1 +/- 6.2 to 46.2 +/- 8.6 mumol/l and 1.96 +/- 0.37 to 3.20 +/- 0.71 pmol/ml in Ca group, 36.0 +/- 5.3 to 54.7 +/- 6.9 mumol/l and 2.45 +/- 0.52 to 2.87 +/- 0.43 pmol/ml in ACEI group, respectively). Either benidipine or trandolapril improves the endothelial function and increases the impaired basal release of NO in hypertension. This suggests the beneficial effects of the drugs on protection against the vascular complications in hypertension.
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PMID:Long-term effect of antihypertensive therapy with calcium antagonist or angiotensin converting enzyme inhibitor on serum nitrite/nitrate levels in human essential hypertension. 1091 45

Angiotensin II (ANG II) has multiple effects on cardiovascular and renal cells, including vasoconstriction, cell growth, induction of proinflammatory cytokines, and profibrogenic actions. Recent studies provide evidence that ANG II could stimulate intracellular formation of reactive oxygen species (ROS) such as the superoxide anion (O2-). This ANG II-mediated ROS formation exhibits different kinetic and lower absolute concentrations than those traditionally observed during the respiratory burst of phagocytic cells, but it likely involves similar membrane-bound NAD(P)H-oxidases. Current evidence suggests that ANG II, through AT1-receptor activation, upregulates several subunits of this multienzyme complex, resulting in an increase in intracellular O2- concentration. ROS are involved in several signal pathways, and redox-sensitive transcriptional factors (AP-1, NF-kappaB) have been characterized. ANG II-induced ROS play a pivotal role in several pathophysiologic situations of vascular and renal cells such as hypertension, endothelial dysfunction, nitrate tolerance, atherosclerosis, and cellular remodeling. Although these perceptions suggest that drugs interfering with ANG II effects (ACE inhibitors, AT1 -receptor antagonist) may serve as antioxidants, preventing vascular and renal changes, the clinical studies are not so straightforward. In fact, only specific risk groups, such as patients with diabetes mellitus or renal insufficiency, may benefit from ACE inhibitors, whereas hard endpoints showed no advantage for ACE inhibitors in patients with essential hypertension.
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PMID:Free radical production and angiotensin. 1098 Nov 45


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