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)

We have demonstrated previously that a variety of agents including corticosteroids, thyroid hormone, cationophores, methylxanthines, and analogues of cAMP--all of which have diversified functions in various tissues--elevate cellular angiotensin converting enzyme (ACE) activity of bovine endothelial cells in culture. In addition to these agents, we have now found that direct and receptor-mediated stimulators of adenylate cyclase, i.e., forskolin and cholera toxin, increase cellular ACE activity after 48 h incubation in culture. In an attempt to search out a more unifying concept of these stimulatory effects, we have further investigated the roles of second messengers in the stimulatory actions. Ca2+ ionophore A23187 produced significant increases in both intracellular Ca2+ and ACE of endothelial cells. In contrast to Ca2+ ionophore, agents that transiently mobilize Ca2+ from intracellular reserves such as bradykinin, acetylcholine, and ATP have no effect on the level of cellular ACE. Representative agents that elevate cellular cAMP (e.g., isobutyl methylxanthine [IBMX] and dibutyryl cAMP) elevated cellular ACE, but the slightly increased [Ca2+]i produced by these agents did not reach statistical significance. While IBMX, cholera toxin, and forskolin elevated cellular cAMP, other ACE stimulatory agents (hormones and cationophores) had no effect on cAMP. Ca2+ ionophore and the agents that elevated intracellular cAMP potentiated the effect of dexamethasone, thyroid hormone, and aldosterone in elevating cellular ACE activity. Increases in ACE activity produced by all stimulants were inhibited by the presence of 10-50 nM ouabain in the culture medium. Inhibition of ACE elevation by oubain was reversed by increasing the extracellular [K+], thereby implicating Na+, K(+)-ATPase in the ACE regulatory mechanism. These results support the presence of multiple independent mechanisms for the regulation of cellular ACE. In addition to possible involvement of intracellular Ca(2+)- and cAMP-dependent pathways, ACE is also increased by corticosteroids and thyroid hormone through mechanisms unrelated to Ca2+ and cAMP.
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PMID:Involvement of second messenger systems in stimulation of angiotensin converting enzyme of bovine endothelial cells. 165 91

With 30 years of experience, it is possible to claim that diuretics are well tolerated antihypertensive drugs producing a significant decrease in systolic and diastolic blood pressure as good as obtained with beta-blockers, converting enzyme inhibitors, calcium antagonists and centrally acting drugs. Recently diuretics have been criticised because of a substantial number of important side-effects, and are disregarded by some authors as first-line agents for the treatment of mild hypertension. Diuretics seem however safe in the majority of hypertensive patients who do not present special problems. Using low doses, which are equally effective, most toxic properties can probably be avoided. Combination therapy, especially with ACE inhibitors, has not only additional effects, but lowers also the potential adverse effects, caused by diuretics. We are convinced that diuretics are still important as first-line agents for the treatment of arterial hypertension in the general population.
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PMID:Diuretics in the treatment of hypertension. 166 46

Ideally, an antihypertensive agent should have a neutral effect or, preferably, produce a favorable shift in the serum lipid and lipoprotein profile, which is associated with a decrease in coronary heart disease risk. The thiazides and loop diuretics increase total lipid levels, low-density lipoprotein (LDL) cholesterol, and triglycerides. beta-Blockers without beta 2-agonist properties increase triglycerides and decrease high-density lipoprotein (HDL) cholesterol levels. Calcium antagonists, angiotensin converting enzyme inhibitors, and combined alpha/beta-blockers are generally thought to have little effect on the lipid profile, although some studies have indicated a modest beneficial effect. alpha-Adrenoceptor antagonists are known to reduce LDL cholesterol levels modestly and to increase HDL cholesterol levels. The overall results of the currently available studies with celiprolol, a selective beta 1-antagonist with ancillary beta 2-agonist and vasodilating properties, indicate a favorable effect of the drug on serum lipid and lipoprotein profiles.
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PMID:The effects of cardioselective vasodilating beta-blockers on lipids. 167 28

In 1985, an assessment of arterial hypertension treatment in insulin-treated diabetic patient gave disappointing results. In 1988, we carried out another study in order to assess the impact of new antihypertensive drugs (angiotensin converting enzyme inhibitors and calcium antagonists) on the management of arterial hypertension and to identify patients in whom strict normal blood pressure control is mandatory. Seven hundred and fifty four patients were selected. The prevalence of arterial hypertension was 38.4 p. 100 (n = 290). Two hundred and thirty five patients (31.2 p. 100) were on antihypertensive treatment: monotherapy: 60.4 p. 100 (n = 142), bitherapy: 30.6 p. 100 (n = 72), tritherapy: 9 p. 100 (n = 21). In descending order of frequency, the following drugs were used: angiotensin converting enzyme inhibitors, calcium antagonists, diuretics, cardio-selective beta-blockers, central acting agents. Blood pressure values significantly decreased (148/83 mmHg, in 1988, vs 157/85 mmHg, in 1985, p less than 0.05). However, 20 p. 100 of the patients still had blood pressure values greater than or equal to 160 and/or 95 mmHg with or without antihypertensive treatment, and on average, blood pressure values remained higher in patients with antihypertensive treatment than in those without (148/83 mmHg vs 131/77 mmHg, p less than 0.001). Patients with urinary albumin excretion above or equal 30 mg/24 h compared to those with normal albuminuria had significant higher values of blood pressure, glycosylated haemoglobin and blood lipids (p less than 0.01). Only 51 p. 100 of these patients, received an antihypertensive treatment. This study emphasizes the difficulty of antihypertensive treatment in insulin-treated diabetic patients and the necessity to improve education in patients with high risk for widespread angiopathy, and particularly those with increased urinary albumin excretion.
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PMID:[Treatment of arterial hypertension in insulin-treated diabetic patients. Change over 3 years (1985-1988)]. 167 85

Therapeutic agents for the treatment of hypertension in the elderly are the well known basic antihypertensive drugs (Diuretics, beta-blocking agents, calcium antagonists and ACE-inhibitors). Choice is determined by concomittant diseases increasing with age. In the elderly patient the assessment of benefit and risk is particularly essential. Drugs should therefore not be installed without exact information of the patient and be started at the smallest possible dose. If tolerance is good the dose may be raised of prescription of an additional drug be evaluated cautiously.
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PMID:[Hypertension in the old age: how to treat it?]. 167 86

Reduction of morbidity and mortality has been the aim of drug treatment for hypertension since its beginning in the 1950s. Its efficacy has been tested in many trials. An outstanding result of these trials has been their clear success in preventing stroke and stroke-related deaths and in decreasing the incidence of congestive heart failure (CHF) and renal disease. A similar success has not been achieved in reducing coronary heart disease endpoints. Diuretics and beta-blockers played a central role in these studies; however, their adverse effects on lipid metabolism have been cited as a possible explanation for the failure of antihypertensive therapy to affect coronary heart disease (CHD). Recently, the extent and significance of these lipid changes has been put into perspective, and new insights into the role of carbohydrate metabolism and insulin resistance in hypertension have emerged. The same drugs which adversely affect lipid metabolism also adversely affect carbohydrate metabolism, and more is becoming known about these mechanisms and their role in hypertension and its sequelae. Other classes of antihypertensive drugs such as the calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, and alpha 1-antagonists do not share these adverse effects. It has become increasingly clear that effective antihypertensive therapy includes both the lowering of blood pressure and containment of the abnormalities that accompany the hypertensive state.
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PMID:Metabolic consequences of treating hypertension. 168 Mar 46

Using whole blood from man and rabbits, the effect of diltiazem, its metabolites, and other calcium antagonists on the uptake of adenosine has been described. The uptake and metabolism of adenosine was extremely rapid with a half-life in plasma of less than 30 s. Adenosine is rapidly and extensively metabolized to hypoxanthine. Metabolites of diltiazem, deacetyl diltiazem and deacetyl O-desmethyl diltiazem were considerably more potent than the parent drug. Diltiazem was one-tenth as active as verapamil, but more active than nifedipine or amlodipine. Dipyridamole was the most potent uptake-inhibitor tested (IC50 less than 1 microM), whereas the angiotensin converting enzyme inhibitor enalapril was virtually devoid of any inhibitory activities (IC50 greater than 1000 microM). The results obtained from both man and rabbit were similar.
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PMID:Effect of diltiazem and its metabolites on the uptake of adenosine in blood: an in-vitro investigation. 168 42

The three approaches (physiopathological, epidemiological and pharmacological) to the management of hypertension should converge to provide a personalized prescription of the most appropriate treatment to prevent and/or cure the cardiovascular complications of hypertension: hypertensive left ventricular hypertrophy and the risks directly related to it (haemodynamic, arrhythmic, ischaemic) may be corrected by certain antihypertensive agents (methyldopa, ACE inhibitors, some calcium antagonists) although there is no proof as yet of the benefits of this intervention (which could suppress the adaptation to the increased wall stress of the left ventricle); malignant hypertension and its cardiovascular complications have almost disappeared with modern antihypertensive therapy. Cardiac failure can be effectively prevented and cured when exclusively related to hypertension. When diastolic pressures are lowered by 8-10 mmHg cerebrovascular risk is reduced by a half and coronary risk by a quarter. Cardiovascular mortality related to hypertension is thus reduced by 20% and total mortality is thereby significantly decreased; the large scale clinical trials which provided these data were performed in the years 1965-1985 with diuretic therapy relayed by (or compared with) betablockers from 1980 onwards. These two families remain the drugs of reference in the prevention and treatment of the cardiovascular complications of hypertension. Personalized description of antihypertensive therapy should take into account the degree of risk and previous cardiovascular complications of the hypertensive patient: betablockers eventually associated with calcium antagonists are to be preferred in cases of hypertension with coronary artery disease and/or arrhythmias, severe hypertension and hypertension complicated by cardiac failure are good indications for ACE inhibitors without prejudicing other therapeutic options necessary in certain contexts, in particular aspirin therapy in patients with previous transient ischemic cerebral attacks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of hypertension and cardiovascular complications]. 168 21

In this article, the issues involved in the measurements of quality of life in clinical trials of cardiovascular drugs are discussed with emphasis on beta-blocker treatment. The extensive documentation available for beta-blockers makes it possible to evaluate different aspects of this class of drugs. Generally, beta-blockers have been shown to be safe with a low frequency of serious side effects. However, results of different studies have shown that this class of drugs affects various aspects of well-being and psychomotor tests both negatively and positively. Adverse effects often associated with beta-blockers are the subjective symptoms that are considered to be related to the central nervous system. Today there is increasing evidence that these can be quantitatively as well as qualitatively reduced by using beta-blockers in a low dose and avoiding high plasma peak concentrations. Considering effects on well-being and psychomotor tests, there seems to be no clinical difference between hydrophilic and lipophilic beta-blockers, when administered in comparable therapeutic dosages, whereas beta 1-selective blockers in clinically relevant doses seem to produce fewer and less severe adverse effects than nonselective blockers. Compared with other classes of cardiovascular drugs, there is no clear evidence of differences in well-being between selective beta-blockers and angiotensin converting enzyme inhibitors or calcium antagonists.
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PMID:Quality of life in cardiovascular diseases. Emphasis on beta-blocker treatment. 168 5

Patients with hypertension requiring therapy frequently present with concurrent peripheral vascular disease (PVD). This situation must be taken into account for an optimum antihypertensive treatment. In general, in patients with PVD only a cautious and gradual lowering of the blood pressure is recommended, since the decrease in poststenotic perfusion pressure may accentuate the symptoms of occlusive disease. In intermittent claudication--the most frequent manifestation of occlusive disease beta--receptor blockers today are no longer considered to be contraindicated. In the presence of critical ischemia of the legs (pain at rest and/or necroses) beta blockers should only be given with extreme caution. The agents of choice are calcium antagonists, ACE -inhibitors as well as alpha blockers and some newer vasodilating substances (e.g. Carvedilol). Conventional diuretics show disadvantages. An slightly elevated blood pressure in critical leg ischemia helps to improve the poststenotic perfusion of the affected limb. Antihypertensive treatment should not be instituted in patients whose systolic blood pressure is lower than 160 mmHg.
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PMID:[Antihypertensive therapy in arterial occlusive disease]. 168 38


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