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)

Congestive heart failure (CHF) is growing epidemiologic and clinical problem, and is the only common cardiovascular condition that is increasing in incidence, prevalence and mortality. During last years numerous clinical trial have been conduced evaluating the effect of various treatment procedures on clinical endpoints in patients with CHF. The major risk factor for CHF are hipertension and atherosclerotic vascular diseases, and now it is clear that aggressive treatment of hypertension and hyperlipidemia can be effective in preventing CHF. Treatment strategies for CHF are aimed at preventing and delaying progression of the disease and improving survival. In the treatment of CHF diuretics are at present the first drugs line for patients with fluid retention and are necessary to relieve symptoms but cannot halt progression or improve the prognosis of CHF. Angiotensin-converting enzyme inhibitors (ACE inhibitors) therapy has been shown to decrease mortality and progression of CHF and should be used early in patients with left ventricular dysfunction whether they have symptomatic or asymptomatic CHF. Digoxin therapy is associated with decrease in the risk of worsening CHF irrespective of rhythm, systolic function, severity of CHF or therapy with ACE inhibitors. In patients with symptomatic CHF due to systolic dysfunction the addition of diuretics and digoxin appears to reducing worsening CHF without improving survival. Other than digoxin oral inotropic agents (amrinone, pimobendan, vesnarinone, ibopamine) increase mortality in patients with CHF and have not improved symptom status and other clinical endpoints during long-term therapy. Hydralazine and isosorbide dinitrate administrated in combination are less effective alternative to ACE inhibitors. Beta-blockers and particular carvedilol may prolong survival and decrease worsening CHF when used in combination with digoxine, diuretics and ACE inhibitors. Beta-blockers therapy improve hemodynamics, LVEF and functional status patients with CHF and the ideal candidate for this therapy is stable patients with NYHA II-III CHF due to nonischemic cause. Calcium antagonists do not appear to be useful in patients with CHF, although amlodipine and mibefradil appears to be safe for treatment of angina or hypertension in this group. On the basis of current data, antiarrhythmic agents should not be given to patients with CHF free from arrhythmia but those with sustained ventricular tachycardia or ventricular fibrillation amiodaron appears to be safe.
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PMID:[Trends in pharmacological treatment of congestive heart failure]. 1036 2

In children with large left-to-right shunts secondary to congenital heart defects the imbalance between the pulmonary and systemic perfusion may lead to circulatory congestion with clinical signs similar to those of heart failure. The circulatory function in this state was evaluated by using the invasive measurements performed during cardiac catheterisations in n = 64 young patients with ventricular septal defect (n = 56) or complete atrioventricular septal defect (n = 8) aging 0.1-23.7 years (median 1.1 years). The mean shunt ratio was Qp/Qs = 2.4 (range 1-8). With increasing shunt ratio the pulmonary perfusion raised (r = 0.84), but the systemic output dropped significantly (r = -0.77) while the total cardiac output (Qp + Qs) increased slightly not exceeding 141/min/m2. In infants, the systemic hypoperfusion affects the hemoglobin content: Hb = 14.9-1.01 x Qs, r = 0.63, p < 0.01. This may be due to the diminished oxygen extraction reserve of 46%. With dropping systemic output, the vascular resistance increases and the mean aortic pressure (MAP) remains normal. The actual pressure values layed near to the curve of the normal aortic pressure calculated as MAP = Qs x Rs. This pressure-flow-resistance diagram was used to interpret the effects of vasodilators established by 7 studies: ACE-Inhibitors, Hydralazine, and Na-Nitroprusside reduce the vascular resistance effectively but induce hypotension, because the systemic output fails to increase. In the chronic circulatory congestion secondary to a large intracardiac left-to-right shunt the pulmonary perfusion increases with the shunt ratio but the systemic output decreases and the total cardiac output is limited to a maximum of 141/min/m2. In this state vasodilators cause systemic hypotension thus offering no acceptable therapeutic option.
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PMID:[Circulatory failure in children with left-to-right shunt in the framework of congenital heart defects: pathophysiology and therapeutic results]. 1081 53

Chronic inhibition of endothelial NO synthesis by the administration of N(G)-nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular inflammation (monocyte infiltration into coronary vessels and monocyte chemoattractant protein-1 expression) as well as subsequent arteriosclerosis. The small GTPase Rho controls cell adhesion, motility, and proliferation and is activated by several growth factors such as angiotensin II. We investigated the effect of a specific inhibitor of Rho-kinase, Y-27632, in rats treated with L-NAME to determine the role of the Rho/Rho-kinase pathway in the development of arteriosclerosis. We found here increased activity of Rho/Rho-kinase after L-NAME administration and its prevention by angiotensin II type 1 receptor blockade. Hydralazine or lecithinized superoxide dismutase (l-SOD) did not affect Rho/Rho-kinase activity. Co-treatment with Y-27632 did not affect the L-NAME-induced increase in cardiovascular tissue ACE activity or L-NAME-induced decrease in plasma NO concentrations, but did prevent the L-NAME-induced early inflammation and late coronary arteriosclerosis. In addition, Y-27632 prevented the increased gene expression of monocyte chemoattractant protein-1 and transforming growth factor-beta1 as well as cardiac fibrosis and glomerulosclerosis. These findings suggest that increased activity of Rho/Rho-kinase pathway mediated via the angiotensin II type 1 receptor may thus be important in the pathogenesis of early vascular inflammation and late remodeling induced by chronic inhibition of NO synthesis. The beneficial effects of Rho-kinase inhibition are not mediated by restoration of NO production. The Rho-kinase pathway could be a new therapeutic target for treatment of vascular diseases.
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PMID:Important role of Rho-kinase in the pathogenesis of cardiovascular inflammation and remodeling induced by long-term blockade of nitric oxide synthesis in rats. 1184 92

The renin angiotensin system plays an important role in growth and development. Exposure of the neonate to an ACE inhibitor increases mortality and results in growth retardation and abnormal development. We have demonstrated that ACE inhibition in the developing kidney increases apoptosis and decreases cell proliferation, which may account for renal growth impairment. To evaluate the role of endogenous angiotensin in cardiac development, the relationship between ACE inhibition, cell proliferation, apoptosis, several modulators of apoptosis (bcl-2, bcl-xl, and clusterin) was examined in the developing rat heart. Thirty-five newborn rat pups were treated with enalapril (30 mg/kg/d) or a vehicle (control group) for 7 d, and hearts were removed for rt-PCR and Western blotting of bcl-2, bcl-xl, and clusterin. An additional 10 rat pups were treated with hydralazine (10 mg/kg/d) or a vehicle, to serve as a hypotensive control. Cell proliferation was determined by PCNA immunostaining, and apoptosis was detected using the total TUNEL technique. Enalapril treatment resulted in a 24% mortality, reduced body weight, and decreased heart weight (p < 0.05). Enalapril decreased proliferating myocytes by 23%, and reduced proliferating cardiac interstitial cells by 8.1% (p < 0.05). Enalapril also decreased myocytes apoptosis by 60%, but the proportion of myocytes undergoing apoptosis was 10-fold less than that of proliferating cells. Cardiac bcl-2 mRNA, clusterin mRNA, bcl-2 protein, and bcl-xl protein content were not changed, but clusterin protein expression was decreased by enalapril treatment. Hydralazine did not alter cardiac cell proliferation or apoptosis. We conclude that ACE inhibition decreases cell turnover in the developing rat heart, which may contribute to cardiac growth impairment. The loss of myocytes may lead to greater myocyte hypertrophy and myocardial damage during later life.
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PMID:Angiotensin converting enzyme inhibition decreases cell turnover in the neonatal rat heart. 1219 62

Heart failure is an established predictor of primary cardiac events during pregnancy. Adequate heart failure treatment in pregnant women is hampered by important foetotoxicity of several conventional drugs. Hydralazine with or without long-acting nitrates has been proposed as an alternative for ACE inhibitors or angiotensin receptor blockers. There are no published data, however, on the use of hydralazine to treat heart failure during pregnancy. We describe the course and outcome of pregnancy in two patients with heart failure. A 31-year-old woman with dilated cardiomyopathy was not treated with hydralazine during pregnancy and developed worsening heart failure. A 36-year-old woman with ischaemic cardiomyopathy was treated with hydralazine early during pregnancy and remained stable throughout and after pregnancy. We assume that early initiation of hydralazine as an alternative for ACE inhibitors or angiotensin receptor blockers during pregnancy in patients with cardiomyopathy could prevent further left ventricular dilatation and worsening heart failure.
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PMID:Treatment of pre-existing cardiomyopathy during pregnancy. 2478 72


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