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 influence of sympathectomy of the ear artery in rabbits on the activity of a number of redox coenzymes inthe vascular wall (lactic, glucose-6-phosphoric, isocitrate, and succinic dehydrogenases: LDH, G-6-PDHm isoCDH, and SDH, respectively) was studied by the quantitative histochemical method. Sympathectomy produced a significant diminution of all the dehydrogenase activities. The effect of adrenalin and noradrenaline on the dehydrogenase activities differed. Adrenalin increased thI LDH activity in the intact perfused artery, but had no effect on the CDH and G-6-PDH. Contrary to adrenalin, noradrenaline increased not only the LDH activity, but also that of the G-6-PDH. The action of noradrenaline on the sympathectomized vessel depended on the place of noadrenaline entrance, i.e. through the intima or the adventitia.
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PMID:[Effect of desympathization and catecholamines on metabolic processes in the rabbit otic artery]. 88 11

ISH is a distinct pathogenetic entity defined by SBP readings of greater than or equal to 160 and DBP less than 90 mmHg. The etiology, although not well understood, is in some manner related to a reduction in connective tissue elasticity of large blood vessels and an increase in aortic impedance or a decrease in aortic wall compliance. The pathophysiologic consequences include an increased resistance to systolic ejection of blood and a disproportionate increase in SBP. Although not directly related, there is an important increase in peripheral vascular resistance. The prevalence of ISH in several studies is about 7 percent in those over age 60 and increases with age to nearly 20 percent in those over age 80. There is higher prevalence in females and nonwhites. The guidelines for detection of ISH are similar to those for blood pressure evaluation in general. Precautions for detection and evaluation in the elderly include multiple blood pressure measurements in the fasting state and sitting and supine blood pressure measurements before and during therapy. Pseudohypertension, although rare, should be kept in mind. There is a clear risk associated with ISH for stroke, CVD, and premature death, which increases with age and rising levels of SBP. ISH can be controlled effectively with pharmacologic therapies. A reasonable goal is a 20 mmHg reduction in systolic pressure. Proof of reduced risk for stroke, CHD, and death in those with controlled ISH remains to be demonstrated. The SHEP pilot study has demonstrated feasibility of addressing this issue. The full-scale SHEP study addresses this issue and has completed recruitment of the desired sample size and is in follow-up phase. Scheduled completion is in 1991. While we wait for the SHEP full-scale trial results, the prudent approach is for nonpharmacologic therapy and use of pharmacologic agents in that group of patients who demonstrate a large cardiovascular risk burden or increasing symptoms specifically associated with hypertension. The decision to treat must be on an individual patient basis. Pharmacologic therapy is possible in most patients with few or no adverse effects. The "low and slow" approach to therapy is helpful in minimizing these adverse effects. Low-dose diuretics have been documented to be effective in blood pressure control. Chlorthalidone, 12.5 or 25 mg per day, is suggested. Other agents, such as beta-blockers, reserpine, ACE inhibitors, and calcium channel blockers, are best used as Step 2 agents.
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PMID:Systolic hypertension in the elderly: controlled or uncontrolled. 218 67

Table 1 shows how the five major drug groups interact with those variables which should be especially considered when treating the hypertensive diabetic. While diuretics are sometimes required in severely hypertensive cases-particularly when fluid retention is part of the clinical picture, and beta blockers are the outstanding choice for those with active CHD- the newer agents, particularly ACE inhibitors and alpha blockers, appear, in theory, to be better agents in terms of preventing the major adverse cardiovascular events to which diabetics are so prone. These two types of agents are very effective together and the addition of a calcium antagonist is likely to control the blood pressures of the vast majority of patients. However, one or more randomized controlled trials to evaluate whether recommendations such as these are valid is desperately needed. Meanwhile, each physician is left to make his or her own best estimate as to which drug to use and at what threshold.
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PMID:Managing the diabetic hypertensive patient. 880 60

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

The use of hypolipidemic drugs has been analyzed in 1,113 patients after myocardial infarction using a questionnaire with data entered from the medical records by spa physicians. 80.1% of patients had total cholesterol values > 5.2 mmol/l; mean value being 6.16 +/- 1.08 mmol/l. Mean values of LDL-cholesterol were 4.05 +/- 0.1 mmol/l, of triglycerides 2.01 +/- 1.14 and of HDL-cholesterol 1.26 +/- 0.61 mmol/l. Hypolipidemic drugs were used only in 16.5% patients with total cholesterol values above 7.0 mmol/l, in 14.4% patients with total cholesterol values 6.2-7.0 mmol/l and in 11.4% of patients with cholesterol values 5.2-6.2 mmol/l. Even some patients with cholesterol more than 8.0 mmol/l were not treated by hypolipidemic drugs. The most frequently used drugs were fibrates (phenofibrate, gemfibrozil)--in 89.5% patients. Statins were used only in 7.5% patients receiving hypolipidemic drugs. Our results show that in contrast to the US and European Recommendations for hypolipidemic drug therapy in patients with CHD, this treatment is still infrequently used by Czech cardiologists and internists. This discrepancy is even more apparent when comparing it with other life prognosis improving drug therapies in this group of patients. Antiplatelet drugs, mainly ASA were used in 85.5% patients, beta-blocking drugs in 59.3% patients and ACE inhibitors in 55.9% patients with left ventricular systolic dysfunction. Thus hypolipidemic therapy in CHD is the key problem of drug therapy in patients after myocardial infarction in the Czech Republic.
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PMID:[Use of drug therapy in hyperlipidemia in patients after myocardial infarct in the Czech Republic]. 960 32

Essential hypertension is, at least in many subjects, associated with a decrease in insulin sensitivity, whereas glycemic control is (still) normal. Metaanalyses of hypertension intervention studies revealed different efficacy of treatment on cerebral (cerebrovascular accidents [CVA]) and cardiac (coronary heart disease [CHD]) morbidity and mortality. Although CVA were reduced to an extent similar to that anticipated, the decrease in CHD was less than expected. These differences are likely to be caused by the different impact of concomitant cardiovascular risk factors, such as dyslipidemia, impaired glucose tolerance, and non-insulin-dependent diabetes mellitus on CHD and CVA. Frequently these cardiovascular risk factors are ineffectively controlled in hypertensive patients, and moreover, some of the widely used antihypertensive agents have unfavorable side effects and further deteriorate these particular metabolic risk factors. Therefore, the metabolic side effects of antihypertensive treatment have received more attention. During the past few years, studies demonstrated that most antihypertensive agents modify insulin sensitivity in parallel with alterations in the atherogenic lipid profile. Alpha1-blockers and angiotensin converting enzyme inhibitors were shown to either have no impact on or even improve insulin resistance and the profile of atherogenic lipids, whereas most of the calcium channel blockers were found to be metabolically inert. The diuretics and beta-adrenoreceptor antagonists further decrease insulin sensitivity and worsen dyslipidemia. The mechanisms by which beta-adrenoreceptor antagonist treatment exert its disadvantageous effects are not fully understood, but several possibilities exist: significant body weight gain, reduction in enzyme activities (muscle lipoprotein lipase and lecithin cholesterol acyltransferase), alterations in insulin clearance and insulin secretion, and, probably most important, reduced peripheral blood flow due to increase in total peripheral vascular resistance. Recent metabolic studies found beneficial effects of the newer vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. In many hypertensive patients, elevated sympathetic nerve activity and insulin resistance are a deleterious combination. Although conventional beta-blocker treatment was able to take care of the former, the latter got worse; the newer vasodilating beta-blocker generation seems to be capable of successfully treating both of them.
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PMID:Antihypertensive therapy and insulin sensitivity: do we have to redefine the role of beta-blocking agents? 979 45

Insulin action starts with binding to a membrane receptor (insulin receptor-tyrosine kinase) and with activating an insulin receptor substrate 1 (IRS-1) and substrate 2 (IRS-2). Insulin receptors interact at least with three cascade reactions, phosphorylating G proteins and IRS-1, that activate PLC "ras" and PI-3-K. NIDDM can be defined as a disease caused by defective transduction of insulin signals and IR as a complex phenotype manifesting itself, emphasized by individual and environmental factors, in the cellular systems of signal transduction. IRS is a syndrome characterized by NIDDM, hypertension, visceral obesity, CHD: the X syndrome. Up to day the described mutations of the insulin-receptor gene are rare (e.g. the leprechaunism): genetic IR. Obesity is the principal cause of IR by receptorial and post-receptorial defects: metabolic IR. The obese skeletal muscle shows a reduction of insulin receptor and IRS-1 phosphorylation and of PI-3-K activation; the scarce expression of these proteins would determine the muscular IR. IR is a pattern of essential hypertension. Hypertension, dyslipidemia and abnormality of glucose metabolism are linked by IR. The so called high erythrocyte Na(+)-Li+ counter-transport is a new biochemical marker for IR and hypertension. These drugs can reduce IR: metformin, sulphonilureas, fibrats, dexfenfluramine, troglitazone, doxazosin, ACE-inhibitors.
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PMID:[Insulin resistance. Receptor and post-receptor abnormalities]. 984 54

Essential Hypertension (EH) is a multifactorial and polygenic syndrome with a high impact in public health. Recently, rare mendelian forms of hypertension such as glucocorticoid-remediable aldosteronism (GRA), apparent mineralocorticoid excess (AME) and Liddle Syndrome caused by single gene mutations have been identified in which the mechanism is an increased sodium retention. Therefore, it is tempting to speculate that the most common forms of EH may be due to diverse highly prevalent molecular variants of susceptibility genes with low penetrance that are involved in arterial blood pressure (ABP) and electrolytic balance. Although a number of candidate genes such as NO synthases, ANP, ion transporters, adducins, LDL receptor, etc. can participate, renin-angiotensin system components are the most extensively studied. Although not associated with EH, the ACE D allele seems to confer a high risk of CHD or LVH. Angiotensinogen 235T and 174M variants are more likely associated with EH and positively correlate with clinical or ambulatory ABP in adolescents or adults. Individuals who carry these angiotensinogen alleles would be at 1.4 higher risk of suffering EH than homozygotes for M235 or T174 alleles. Associations of AT1 receptor variants with EH remain to be definitively defined. In conclusion, the characterization of the genetic background, although difficult at the present time, may have clear benefits in terms of defining a more rational therapy and prevention in individuals at risk. Even though this aim seems difficult to achieve since more than 150 candidate genes have been postulated as the cause of EH, with 6 to 10 SNPs in each of them, new technologies such as DNA micro-arrays will provide us with the opportunity to analyse the total genetic risk in each subject.
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PMID:[Molecular genetics of essential hypertension. Susceptibility and resistance genes]. 1083 1

The state of pharmacotherapy in the Czech Republic in 1998 was analysed in a group of 548 patients with coronary heart disease and diabetes mellitus. 83.0% of the group were treated by antiplatelet drugs, mostly ASA (with the most frequent dose being 100 mg). 7.3% of the patients were treated by anticoagulation treatment. Beta-blocking agents were used in 56.9% of the group (most frequently metoprolol and atenolol). The optimal dose of metoprolol, 100 mg b.i.d., was used in only 12.4% of the patients treated by metoprolol. Older patients and patients with left ventricular systolic dysfunction were treated significantly less frequently than younger patients or patients without left ventricular systolic dysfunction. ACE inhibitors were used in 52.2% of the patients. The optimal daily target dosages of captopril 100-150 mg were used in only 6% of patients treated by captopril. The optimal target daily dosages of enalapril were used in only 35.1% of patients treated by enalapril. 65% of patients with left ventricular systolic dysfunction were treated by ACE inhibitors. Calcium-channel blockers were used in 24.6% of the patients. However, in 20.1% of patients treated by calcium-channel blockers, shortacting or inadequately retarded nifedipine was used. 69.8% of the patients had total cholesterol values higher than 5.2 mmol/l, 18.1% higher than 6.2 mmol/l and 13.5% of patients had total cholesterol values higher than 7.0 mmol/l. 34.3% of the group were treated by hypolipidemic drugs (most frequently fenofibrate). Statins were used by 45.5% of patients treated by hypolipidemic drugs. When compared to our analysis of pharmacologic treatment in patients after myocardial infarction, performed in 1995, ACE inhibitors and hypolipidemic treatment are used more frequently. However, in spite of this improvement, only about 15% of patients with CHD are treated by statins. Furthermore, 35% of patients with left ventricular systolic dysfunction due to CHD are not treated by ACE inhibitors. Elderly patients with CHD and diabetes mellitus or patients with left ventricular systolic dysfunction due to CHD are less frequently treated than younger patients or those with normal left ventricular systolic function despite the fact that patients at highest risk benefit most from treatment with beta-blocking agents. Also unsatisfactory is the use of not retarded or inadequately retarded nifedipine although data show its use may increase total mortality in CHD patients. By contrast, use of antiplatelet therapy is satisfactory.
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PMID:[Pharmacotherapy in patients with ischemic heart disease and diabetes mellitus in 1998 in the Czech Republic]. 1095 43

Diuretics and beta-blockers are presently recommended as first-line therapy for the treatment of uncomplicated hypertension. JNC VII will probably consider ACE inhibitors worthy of this recommendation. In those at high risk for CHD or CHF, the initial use of an alpha-blocker or calcium antagonist will be recommended with caution. In those with systolic hypertension, who remain at increased risk of stroke, the initial use of CCB therapy continues to be supported by trial-based evidence. A diuretic, based on outcome-based trials, should be included in most regimens to lower the risk of ischemic stroke. Since most patients will require two or more drugs to control their blood pressure, the initial agent chosen will assume less importance for the practicing physician.
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PMID:Hypertension 2001: pearls for the clinician. 1178 Jun 73


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