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)

The authors review the drug treatment of Raynaud's disease. Many substances have been used including nitrate derivatives, calcium antagonists, alpha blockers, angiotensin converting enzyme inhibitors, prostaglandin E1, E2 and I2, and ketanserin. The efficacy of these drugs is often partial and variable. The indications are discussed with respect to the clinical course and etiology of the Raynaud's phenomenon.
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PMID:[Medical treatment of Raynaud's syndrome]. 306 74

Therapy combining vasodilators and inotropic agents is considered to be one of the most powerful means of improving cardiac function in patients with congestive heart failure (CHF). The vasodilators enhance the effectiveness of inotropic agents by providing a reduction in preload and/or afterload. Inotropic drugs with different mechanisms of action, such as digitalis glycosides, ephedrine, dopamine, dobutamine, ibopamine, terbutaline, salbutamol, pirbuterol, prenalterol, amrinone, and milrinone, have been tested in combination with vasodilators with a predominant effect on preload (nitrates, molsidomine), with a predominant effect on afterload (hydralazine, nifedipine), or with a balanced action on both arterial and venous beds (nitroprusside, prazosin, captopril), showing positive results. The problem of the combination of digitalis glycosides and vasodilators with different sites of action has been considered by our group. In 42 patients with CHF, digoxin (DIG, 0.01 mg/kg intravenously) was tested in combination with molsidomine (MLS, 4 mg sublingually) (12 patients), a nitrate-like agent with a predominant vasodilating action on the capacitance vessels, nifedipine (NFP, 10 mg sublingually) (22 patients), a Ca2+ antagonist drug with a predominant action on the resistance vessels, and captopril (CPT, 25 mg orally) (8 patients), an ACE inhibitor with a balanced effect on both preload and afterload. The combination DIG plus MLS caused a reduction in left ventricular filling pressure (LVFP) greater than that achieved with either agent alone. The hemodynamic improvement was obtained without side effects, in spite of the striking fall in preload. We stress that this investigation was performed on patients with CHF following acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Combination of positive inotropic and vasodilating substances in congestive heart failure. 315 99

The angiotensin converting enzyme catalyzed hydrolysis of furanacryloyl-Phe-Gly-Gly is activated by monovalent anions in the order C1- greater than Br- greater than F- greater than NO3- greater than CH3COO-. In the alkaline pH region, increasing anion concentrations decrease the KM but do not change the kcat. This behavior is characteristic of an ordered bireactant mechanism in which the anion binds to the enzyme prior to the substrate. At acidic pH values, however, the anion activation is a result of both a decrease in KM and an increase in kcat, implying a bireactant mechanism in which anion and substrate bind randomly. For both the ordered and the bireactant mechanisms the anion serves as an essential activator. The effect of chloride on enzyme activity was studied over the pH range 5-10 under kcat/KM conditions and demonstrates that the apparent chloride binding constant increases from 3.3 mM at pH 6.0 to 190 mM at pH 9.0. The kcat vs. pH profile exhibits two pK values of 5.6 and 9.6, while the variation of KM with pH is characterized by a pK of 8.9 and a 2-fold increase between pH 6.5 and 7.5. The chloride activation of the hydrolysis of furanacryloyl-Phe-Gly-Gly is compared with that of the physiological substrates angiotensin I and bradykinin.
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PMID:Activation of angiotensin converting enzyme by monovalent anions. 629 31

There is now little dispute that clinical tolerance of organic nitrates occurs, particularly when these drugs are used by themselves to treat patients with stable angina pectoris and congestive heart failure. Classical hypotheses of nitrate tolerance suggest the phenomenon to result from vascular depletion of critical sulfhydryl groups, which are necessary to bring about vasorelaxation from nitrates. While this mechanism of nitrate tolerance probably operates when isolated blood vessels are exposed to high concentrations of nitrate in vitro, there is little evidence to suggest that it contributes to clinical nitrate tolerance. Instead, emerging data suggest that nitrates can cause significant shifts in fluid distribution and secretion of neurohormonal factors that can modulate their vasorelaxant effects. Use of angiotensin converting enzyme inhibitors and diuretics in conjunction with nitrates may alleviate the development of tolerance, but the experience has not been universally favorable. Other receptor-effector systems that affect cardiovascular function, such as the adrenergic system, may also be affected by nitrate tolerance. The mechanisms of nitrate tolerance are therefore likely to be multifactorial, involving vascular biochemical changes, physiologic compensation, and possibly receptor regulation.
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PMID:Mechanisms of nitrate tolerance. 794 66

Nitrates are commonly used in the therapy of congestive heart failure (CHF). They exert beneficial hemodynamic effects by decreasing left ventricular filling pressure and systemic vascular resistance while modestly improving cardiac output. The improvement in left ventricular function caused by nitrates is the result of combined reduction in outflow resistance and mitral regurgitation, while decreased pericardial constraint and subendocardial ischemia may also contribute to the process. With continuous nitrate administration, complete arterial tolerance develops, while venous tolerance appears to be only partial. The major mechanism of tolerance is loss of vascular smooth muscle sensitivity to nitrates. An increase in total blood volume occurring during the first few hours of an acute administration may partly contribute to tolerance. The importance of reflex neurohumoral activation is controversial; although it may contribute to tolerance in CHF, its role does not appear to be major. Chronic continuous nitrate therapy in CHF improves submaximal and maximal exercise tolerance. In combination therapy with hydralazine, isosorbide dinitrate reduces mortality, although to a lesser extent than the angiotensin converting enzyme inhibitor enalapril. Intravenous or sublingual nitrates are first-line agents in the therapy of acute pulmonary edema. In severe CHF, refractory to standard medical therapy, a short course of intravenous nitroglycerin, with or without inotropic agents, can help break the vicious spiral of CHF. Because tolerance occurs without nitrate-free intervals and until an optimal schedule of administration is determined, it makes good sense to include a nightly nitrate-free interval when prescribing nitrates for CHF in order to maintain maximal benefit during the hours of activity.
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PMID:Nitrates in congestive heart failure. 794 67

In this study, we investigated the potential for reductive dechlorination of chlorophenols by municipal sewage sludge acclimated to 2,4-dichlorophenol (2,4-DCP) and 3,4-dichlorophenol (3,4-DCP). The optimal temperature and pH for dechlorination of 2,4,6-trichlorophenol (2,4,6-TCP) were 30 degrees C and 7.2. Dechlorination of 2,4,6-TCP was inhibited by sulfate, nitrate, or ferric (III), but was increased by manganese (IV) except that product of 2,4-DCP was accumulated. Organic substrates such as pyruvate or acetate did not influence dechlorination of 2,4,6-TCP, but increased dechlorination of 2,4-DCP; nevertheless lactate showed no influence on dechlorination. When glucose was added as substrate, only 20% of 2,4,6-TCP dechlorination was found. Addition of methanogenesis inhibitor 2-bromoethane sulfonate did not influence dechlorination, but addition of eubacteria inhibitor vancomycin showed no dechlorination activity at the first few days, and finally complete transformation and accumulation of 2,4-DCP occurred. Because mixed culture was from Di-Hwa Wastewater Treatment Plant, adding the same water as culture medium was found to increase the dechlorination of 2,4,6-TCP and its product 2,4-DCP. Dechlorination by adding wastewater of Petroleum Corporation was also increased, especially for 2,4-DCP product, but only 7% of 2,4,6-TCP dechlorination was found after incubation with Hou-Chin river water for 14 days.
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PMID:[Reductive dechlorination of chlorophenols by an anaerobic mixed culture]. 798 80

Vasodilator drugs, particularly intravenously infused nitroprusside and an orally administered combination of hydralazine and isosorbide dinitrate, exert a profoundly favorable hemodynamic effect in the setting of heart failure complicating a prior myocardial infarction. Although these oral drugs also may relieve symptoms and improve exercise tolerance, the long-term benefits appear to be related to inhibition or reversal of the left ventricular dilation that results in a progressive fall in left ventricular ejection fraction. The long-term efficacy of both ACE inhibitors and hydralazine-nitrate in symptomatic heart failure makes the vasodilator combination a rational alternative to an ACE inhibitor and possibly an effective agent for cotherapy with an ACE inhibitor. Trials are needed to test the additive efficacy of this vasodilator combination and to develop other safe and effective drugs that target the progressive remodeling process in heart failure.
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PMID:Treatment of infarct related heart failure: vasodilators other than ACE inhibitors. 808 21

The early administration of nitrates in acute myocardial infarction (AMI) may lower myocardial oxygen demand and increase blood supply to the ischemic myocardium. Actually, nitrates are the drugs most largely used in AMI patients, but no definite proof of their clinical benefits had been reported before GISSI 3 and ISIS 4. Only a meta-analysis of several trials carried out before the thrombolytic era showed that intravenous nitrates and probably oral nitrates can reduce mortality when given early to patients with myocardial infarction. The adjunctive benefit of nitrates in AMI patients receiving the treatments recommended today (thrombolysis, aspirin, beta-blockade) remained undefined. Accordingly, two large controlled randomized studies--GISSI 3 and ISIS 4--were undertaken to verify benefits and risks of nitrate strategy vs ACE-inhibition strategy in AMI. Overall, about 80,000 patients were enrolled. In both studies a small, non significant decrease of mortality was observed in patients allocated to nitrate arms. In GISSI 3, the mortality reduction was greater in patients receiving both nitroglycerin and lisinopril. Either intravenous or by oral or transdermal route nitrates were well tolerated. In conclusion, the systematic administration of nitrates in acute myocardial infarction induces limited benefits in relation to the strategy based on the clinically indicated nitrate administration (applied in 60% of the control patients) but does not bring up risks.
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PMID:[Are nitrates to be recommended in acute myocardial infarct? Towards a conclusive answer]. 808 20

Organic nitrates have been used widely in the treatment of chronic congestive heart failure. These drugs have been shown to have beneficial hemodynamic effects both at rest and during dynamic and isometric exercise. In combination with hydralazine, nitrates have been shown to improve exercise tolerance, enhance left ventricular ejection fraction, and prolong survival. The potential limitations of nitrate therapy are related to dose-related nitrate resistance and the development of nitrate tolerance. More information is needed regarding the usefulness of nitrate therapy without hydralazine and the additional benefits of these drugs in patients already treated with angiotensin converting enzyme inhibitors.
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PMID:Nitrates in heart failure. 818 Oct 27

Vasodilator therapy has been utilized for the treatment of congestive heart failure in the last 20 years. These drugs contribute to increase cardiac output, decrease peripheral vascular resistance and favour venous dilatation. Recent multicenter trials have addressed the issue of the impact of vasodilator therapy upon survival. Thus, the VHEFT-I and Consensus studies have shown that both the combination of nitrates and hydralazine and ACF inhibitors improve life expectancy in patients with moderate and severe heart failure. Moreover, the SOLVD study showed that ACE inhibitors improve survival and reduce cardiac events in patients with mild heart failure and depressed myocardial function at the end of 2 years of follow-up. The VHEFT II trial compared the effects of the nitrate-hydralazine combination versus ACE inhibitors upon the clinical course of patients with moderate heart failure. This last trial showed that although nitrates and hydralazine exerted a slightly better benefit upon exercise tolerance and left ventricular ejection fraction, patients that were treated with ACE inhibitors had a significantly reduced mortality. Differences in mortality when both groups of vasodilators drugs were compared were due to reduction of arrhythmias and sudden death. It is likely that this greater benefit obtained with ACE inhibitors when compared to nitrates and hydralazine in heart failure might be due to their favourable effects upon the abnormal neurohormonal activation observed in this syndrome. Thus ACE inhibitors have turned out to be one of the cornerstones in the treatment of congestive heart failure.
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PMID:[Vasodilator agents in chronic heart failure: which is the best option?]. 823 72


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