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)

Long-term effects on insulin sensitivity and leucocyte sodium transport were studied in 42 glucose-intolerant hypertensives on beta-blockers, randomly assigned to continuous beta-blockade (beta group) or a switch to captopril treatment (mean daily dose 69.1 mg) (ACE group). In the ACE group, despite a tendency towards improvement, glucose uptake during the euglycaemic insulin clamp procedure did not change significantly from the baseline value of 4.0(0.5-12.9) mg/kg/min, values at 6 and 12 months being 4.8(1.3-14.7) and 4.4(1.5-9.8) mg/kg/min, respectively: the corresponding values for the beta group were 4.2(1.1-15.3), 3.6(1.2-8.9) and 4.0(1.5-12.0) mg/kg/min. The 22Na efflux rate constant, both baseline and follow-up values, was similar in both groups, and unrelated to insulin sensitivity. Owing to the surprisingly great variation in peripheral glucose uptake, the subgroup with values below the median for the population as a whole (4.9 mg/kg/min) was evaluated separately: those switched to captopril treatment manifested a 60% improvement in glucose disposal at 6 months and persisting at 12 months, the respective values being 2.1(0.5-4.8) (baseline), 3.5(1.3-6.3) and 3.4(1.5-6.1) mg/kg/min, (P = 0.012). The body mass index (BMI) was not significantly affected. Values for BMI, peripheral insulin and triglycerides were higher in the subgroup with glucose disposal below the median than in the subgroup with values above the median. Correlation between BMI and glucose uptake was highly significant (r = -0.75, P = 0.0001). The present findings suggest that captopril may be a better alternative than beta-blockers for treating the highly insulin-resistant, glucose-intolerant patients, predominantly to be found among the overweight.
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PMID:Long-term effects on insulin sensitivity and sodium transport in glucose-intolerant hypertensive subjects when beta-blockade is replaced by captopril treatment. 135 39

The risk for cardiovascular complications is already substantially increased in persons with borderline elevation of arterial pressure (141-159/90-94 mmHg and transiently below). It increases progressively with higher grades of hypertension. The main aim of treatment is thus a significant improvement in survival for the patient. Persons with raised blood pressure (BP) have often additional cardiovascular risk factors such as deranged carbohydrate metabolism, dyslipidemia, left ventricular hypertrophy, smoking and others. Treatment of hypertensive patients should thus not only normalize BP but should at the same time reduce associated risk factors or at least not increase them. Conventional antihypertensive treatment based on thiazides in high doses or beta-blocking agents led to marked reduction of strokes and heart failure, but did not satisfactorily reduce coronary heart disease or sudden cardiac death. It has been suspected that other cardiac risk factors are insufficiently influenced or eventually even deteriorated by conventional therapy, thus counteracting partly a beneficial effect of lowered BP. Beta-blockers however have at least a secondary preventive effect after myocardial infarction. Newer antihypertensive drugs such as ACE-inhibitors, calcium antagonists and alpha 1-blockers reduce left ventricular hypertrophy and are at least neutral with regard to metabolism of lipids and carbohydrates. The non-thiazide diuretic indapamide and the serotonin (S2-) blocker ketanserin likewise are neutral with regard to glucose and lipid metabolism. The efficacy of these new drugs regarding long term survival is as yet undetermined. Persisting borderline or established hypertension should as a rule always be approached with basic non-pharmacologic measures: loss of overweight, reduction of alcohol intake, exercise, avoidance of high salt foods, abstention from smoking and withdrawal of BP-raising drugs. If antihypertensive medication is indicated, potential first line drugs are ACE-inhibitors, calcium antagonists, beta-blockers, thiazides at low dose, indapamide, ketanserin, the alpha 1-blocker prazosin and others; initially as monotherapy, if needed in combinations of 2 or 3. Older patients or those will with additional disturbances such as diabetes, hypercholesterolemia, nephropathy, heart failure, ischemic heart disease, arrhythmias, claudication, asthma and others need problem-adjusted modifications of treatment.
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PMID:[Antihypertensive therapy in the nineties]. 153 54

Arterial hypertension is frequently associated with metabolic abnormalities. Hyperinsulinemia and insulin resistance are found in obese patients, in non-insulin-dependent diabetics and in some hypertensive patients, irrespective of whether the patients are overweight or have diabetes mellitus. Membrane transport abnormalities, such as increased sodium-lithium exchange associated with hypertension are also significantly related to disturbances in lipid metabolism. Increased sympathetic nervous system activity is a well established feature of arterial hypertension and this may also affect glucose and lipid metabolism. The possibility of these metabolic alterations in the hypertensive patient must be taken into account when deciding upon treatment. Attention to diet is mandatory and includes advice to reduce energy, salt and saturated fat intakes and to increase the intake of less digestible fiber and of potassium; alcohol consumption should be limited. Energy expenditure by regular aerobic physical exercise should be encouraged and continuous effort is necessary to help patients stop smoking. In patients with high blood pressure and abnormalities in lipid and glucose metabolism, it is wise to start pharmacological treatment with drugs that are known to be neutral in their metabolic effects, such as calcium antagonists, angiotensin converting enzyme inhibitors or alpha-blocking agents.
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PMID:Metabolic disturbances and antihypertensive therapy. 179

Overweight and obesity may develop in individuals with genetically determined low resting energy expenditure. Drugs are among the recognised precipitating factors. The obesity promoting impact of beta-blockers is, however, less well known. Resting energy expenditure, and thermogenesis induced by stimuli such as meals, cold and heat exposure, stress and anxiety, have a facultative component mediated by the sympathoadrenal system through catecholamines working on beta-adrenoceptors. Treatment with beta-blockers reduces the facultative thermogenesis by 50-100 kcal/d, which corresponds to the weight gain of 2-5 kg/year reported in clinical trials. Treatment with beta-blockers also results in insulin resistance, which may aggravate existing diabetes and elicit diabetes in predisposed patients. Overweight and obesity are frequently complicated with hypertension and angina pectoris, which are often treated with beta-blockers. Obesity is associated with a defective sympathetic activity, and treatment with beta-blockers may further reduce facultative thermogenesis and promote weight gain. The consequence may be aggravation of hypertension, insulin resistance and other atherogenic factors. The causal therapy of android overweight and obesity complicated with diabetes or hypertension is a sufficient weight loss. If pharmacological treatment is inevitable, combined treatment with diuretics and ACE-inhibitors are most appropriate.
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PMID:[Obesity and diabetes as side-effects of beta-blockers]. 197 28

Of various antihypertensive drugs, particularly the unselective as well as the selective beta-receptor blockers but also diuretic drugs unfavourable effects on the lipid metabolism are reported, which above all consist of increases of triglycerides and decreases of HDL-cholesterol. The more modern antihypertensive drugs such as calcium antagonists, alpha 1-receptor blockers or angiotensin converting enzyme inhibitors according to the hitherto existing studies have no significant influence on the serum lipids. The final classification of the antihypertensive drugs regarding their influence on the atherogenic risk by negative changes in the lipoprotein metabolism is, however, at present not yet possible on account of insufficient long-term studies. For the reduction of adequate endangerings dietetic measures, reduction of overweight, physical training and when occasion arises change of the medication are recommended.
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PMID:[Modification of lipoprotein metabolism by antihypertensive therapy]. 266 53

Since the angiotensin converting enzyme (ACE) is identical with kininase II, the reduction of its activity by an ACE-inhibitor such as captopril will not only decrease the concentration of angiotensin II but also elevate the levels of kinins. Although the slight increase of the latter will not contribute to the antihypertensive action of ACE-inhibitors, we are sure today that it exhibits local metabolic effects in cardiac and skeletal muscle tissue. These endogenous kinins have been shown to improve the utilisation of glucose in the human forearm, the whole organism and the isolated perfused rat heart and seem to exhibit their effects via prostaglandins. A cross-over plot of the glycolytic intermediates at the height of phosphofructokinase induced by bradykinin in rat heart and the activation of the purified enzyme from rabbit heart by PGE2 point to an enhanced glycolytic rate as their mode of action. From these findings similar effects under ACE-inhibitors can be assumed. This was investigated in ten non-insulin-dependent diabetics, whose glucose disposal rate was measured by the glucose clamp technique. After 25 mg of captopril their peripheral insulin resistance was significantly improved, which was found to be due to an accelerated rate of glucose uptake into their forearm muscle tissue. To evaluate the clinical relevance of these data, 15 mildly hypertensive, overweight type II-diabetic patients (mean age: 53 years; seven women) were hospitalized. After a seven-day wash-out period, the patients were given 25 mg of captopril twice daily for seven days. During the treatment, systemic kinin concentrations significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Captopril in hypertensive patients with type II diabetes mellitus]. 332 92

Criteria for the diagnosis of exercise hypertension have not yet been established. Published values for blood pressure increase during dynamic exercise in normotensive healthy persons differ greatly dependent on age, sex, heart frequency and load of dynamic exercise. Upper normal systolic values during exercise reach levels between 200 and 230 mm Hg. The incidence of exercise hypertension is therefore reported to range from 1 to 10% of the total population. Follow-up studies show that 10 to 60% of persons with isolated exercise hypertension proceed to chronic arterial hypertension. No results are available on exercise hypertension as a risk factor in contrast to the well-known link between increased systolic and diastolic casual blood pressure and cardiovascular diseases. The development of left-ventricular hypertrophy depends mainly on the average systolic blood pressure during a 24-hour period. Peak values of systolic blood pressure during the day or blood pressure variability are less important. Drug treatment of isolated exercise hypertension is not generally accepted. Non-drug treatment is to be preferred, e.g. weight reduction in overweight, dietary sodium restriction and endurance training. Drug treatment must be considered, if non-drug treatment is unsuccessful and/or risk factors, for example hypercholesterolemia, diabetes, cigarette smoking, or complications of target organs, i.e. coronary heart disease or cerebral infarction, do exist. In antihypertensive treatment of increased exercise blood pressure, the influence of the drugs on the hemodynamic and metabolic parameters must be observed, especially in patients with concomitant coronary heart disease. Increases in blood pressure due to dynamic exercise are better attenuated by antihypertensive drugs than those caused by isometric exercise. The drugs of choice are beta-blockers, preferably beta 1-blockers without ISA. Alternatively, calcium antagonists of the verapamil-type or ACE-inhibitors may be used. In contrast to other antihypertensive drugs, labetalol, calcium antagonists and ACE-inhibitors have no influence on the exercise-induced increase of cardiac index and therefore little effect on the work capacity of the circulatory system.
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PMID:[Differential therapy of exercise hypertension]. 358 8

The metabolic syndrome is characterized by cluster-like occurrence of various risk-factors for vascular disease: overweight, hypertension, hyperlipidemia, hyperproteinuria. In the pathogenesis of this syndrome the peripheral resistance to insulin leading to hyperinsulinemia plays most likely a central role, as the development of individual components of the metabolic syndrome may causally be explained in this way. Various possible explanations exist for the development of insulin resistance: on the receptor level, as a result of changes in the capillary bed or in muscle fiber composition, or resulting from disturbed circulation of muscles. Clinical symptoms of hyperinsulinemia are hypertension, lipodystrophy, and type II diabetes. Patients with metabolic syndrome represent a group at high risk for arteriosclerotic vascular disease. Therapy aims primarily at reduction of hyperinsulinemia as the underlying factor. In particular non-medical intervention plays an important role (reduction of body weight, exercise). In drug therapy of hypertension only such antihypertensives which remain neutral to metabolism should be applied, i.e., ACE-inhibitors which even improve the metabolic condition.
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PMID:[ACE inhibitor in metabolic syndrome]. 785 77

A retrospective analysis of 5,088 hypertensives treated by our Outpatient Clinic, Department of Medicine, University Hospital Split from 1988 through 1990 is presented. Male sex was predominant (about 65%) and almost all the patients (over 95%) were overweight and the majority (over 50%) have had mild hypertension. Essential form was by far the most prevalent type of hypertension (over 95%), while curable forms of secondary hypertension were rare indeed (less than 0.2%). Diuretics and beta blockers, the traditional first-line antihypertensives were the most prescribed drugs (over 60%), while the share of ACE inhibitors, calcium antagonists and alpha blockers was steadily increasing. General measures, such as body weight reduction, salt restriction or cessation of smoking, although obligatory part of the treatment and suggested to each hypertensive, are rarely carried out.
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PMID:[Outpatient approach to arterial hypertension: analysis of ambulatory care of hypertonic patients at the Clinical Hospital Center in Split 1988-1990]. 837 72

Future trends in hypertensive treatment have to rely on our past and present experience with antihypertensive drugs as well as on emerging concepts of blood pressure regulation, on which some new drugs in the "pipeline" are based. Early detection of hypertension, before organ manifestations particularly in the heart, the kidney and the vessels occur, remain mandatory since in most of the patients with mild and moderate hypertension the high blood pressure is not diagnosed at all or treated inadequately. Prevention of cardiac, vascular, renal or metabolic complications has always been better for the patient and less costly than their repair or reparation. Our present treatment goals have often not reached far enough. Normalisation of blood pressure demonstrates only surrogate efficacy of our treatment. Our ultimate goal has to be improvement of total or cerebrovascular or cardiovascular and cardiac mortality. Important steps on that road are the prevention or reparation of cardiac hypertrophy, of the increased extracellular matrix and collagen deposition, the conservation of vascular integrity including both coronary and systemic microangiopathy and macroangiopathy. For the patient this means integrated care of his associated disorders that is of coronary artery disease, diabetes mellitus, lipid disorders, overweight and the metabolic syndrome. True health efficacy (= reduction of total or cerebro- and cardiovascular mortality) has been demonstrated so far only by blood pressure reduction with diuretics (thiazides) and beta-blockers in long term studies, whereas sufficient surrogate efficacy, the lowering of blood pressure, has been demonstrated with almost all the others drugs either in mono- or in combinationtherapy. Together with ACE-inhibitors, which have demonstrated their prognostic value in patients with heart failure of different causes, thiazides (as the most representative diuretic) and betablockade can be considered first line drugs in the treatment of hypertension. Long-term mortality trials for ACE-inhibitors in hypertension are needed, however, to prove that the anticipated benefit from the heart failure megatrials can also be taken for granted for hypertensive patients without coronary artery disease as well. All other drugs should not or not yet be considered first line medication, although treatment behavior in the US and in Europe shows wide-spread use of calcium antagonists in short- and long-acting dihydropyridine type hypertensive patients. No peer reviewed journal has so far published a randomized double-blind trial with the endpoint of total or cardiovascular mortality in hypertension using calcium antagonists. A recent case control study, as well as the preliminary data from MIDAS and GLANT, for which event rates are available in abstract form, suggest that short acting calcium-antagonists of the dihydropyridine type, though controlling blood pressure well, are not reducing mortality but show a trend to increase cardiovascular events particularly when given in higher doses. In contrast the unpublished data from a Chinese megatrial with dihydropyridines (STONE) demonstrate effective blood pressure reduction and benefit in mortality in a population that differs from patients in Europe and in the USA because of the low prevalence of coronary artery disease. No randomized, double blindly acquired data on mortality as the primary end of antihypertensive treatment are yet available for verapamil, diltiazem and the new class of longer acting calciumantagonists. Only when speculating from trials with calcium antagonists in coronary artery disease e.g. the DAVIT II study, one could imagine so far that prognostic benefit may be expected from drugs that do not or very little activate the adrenergic and the renin-angiotensin-aldosterone system and the baroreceptors and reduce or at least maintain heart rate. The need for double blind, randomized trials with the different Ca-antagonists is obvious, before a further w
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PMID:[Retrospective studies and prospects of therapy for hypertension]. 858 97


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