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 purpose of this study was to measure components of the renin angiotensin system in patients with type 1 diabetes mellitus, with and without nephropathy, to study the renal sensitivity to angiotensin II in uncomplicated type 1 diabetes and to investigate the short and long-term renal effects of angiotensin II reduction with angiotensin converting enzyme inhibitors in patients with diabetic nephropathy. In patients with type 1 diabetes without complications, plasma renin activity, angiotensin II and aldosterone levels were normal. In patients with diabetic nephropathy, renin levels were elevated, probably partly as a result of diuretic treatment. However, renin levels were also elevated compared to patients with other renal diseases who had similar treatment and degree of azotemia. The renal sensitivity to angiotensin II was normal in patients with uncomplicated diabetes. The reduction in glomerular filtration rate and renal plasma flow and increases in filtration fraction during A II infusion were equal to those in healthy controls. Nine days' captopril treatment in 15 patients with diabetic nephropathy induced an increase in renal plasma flow and a decrease in filtration fraction. The glomerular filtration rate remained unchanged. During 8 weeks' randomised enalapril or metoprolol treatment in 40 patients with diabetic nephropathy, enalapril treatment reduced proteinuria to half the initial value. Metoprolol treatment had no effect on proteinuria. Furosemide was also used and the dosage was adjusted to give equally effective blood-pressure control in both groups. During long-term treatment with captopril in patients with diabetic nephropathy, the rate of decline in kidney function over time was reduced to one-fourth the initial value even though the blood pressure was only slightly reduced. The renin angiotensin system appears to be functionally intact in diabetes mellitus and interruption by ACE inhibition reduces proteinuria both by blood pressure reduction and by an effect independent of systemic blood pressure. Long-term treatment might protect kidney function in diabetic nephropathy to a greater extent than would be expected from the blood-pressure-lowering effect alone.
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PMID:The renin angiotensin system in diabetes mellitus. A physiological and therapeutic study. 219 80

After improvement of technical equipment continuous ambulatory blood pressure monitoring is more and more used in the diagnosis of hypertension. New fully automatic systems permit a reliable registration and evaluation of 24-h blood pressure profiles. Typical circadian rhythmics of blood pressure, independent of a variability with different grades of activity, can be demonstrated in normotensive persons and also in patients with essential hypertension. Patients with secondary forms of hypertension show a nivellation or offset of circadian blood pressure rhythmics. A study was performed to examine the antihypertensive efficacy of the calcium antagonist Nitrendipine, the beta 1-adrenoceptor-selective blocker Metoprolol, the beta-blocker with intrinsic activity Mepindolol and the angiotensin converting enzyme inhibitor Enalapril in patients with mild to moderate hypertension over a period of 6 month. Continuous ambulatory blood pressure monitoring was performed before and after 6 month of therapy. 98 of 299 included patients broke off therapy, 47 of those because of side effects. Hydrochlorothiazide was given additionally if the antihypertensive effect of monotherapy was not sufficient after a period of 4 weeks. Morning blood pressure controls at the end of the treatment period showed normotensive values in all groups without significant differences between the groups before and at the end of the treatment period. The number of prescriptions of diuretics necessary to achieve normotension differed between the four treatment groups: Nitrendipine (n = 5), Metoprolol (n = 7), Mepindolol (n = 14), Enalapril (n = 20). In contrast to the morning blood pressure values the continuous 24-h blood pressure monitoring demonstrated significant differences between the therapy groups. Metoprolol turned out as most effective in lowering blood pressure and in reducing the number of systolic blood pressure peaks above 180 mmHg, but on the other hand showed the highest incidence of relative hypotension (less than 100 mmHg systolic, less than 80 mmHg diastolic). Mepindolol demonstrated a significant lower efficacy. In the Nitrendipin group least of all prescriptions of diuretics were necessary and the lowest number of hypotensive systolic blood pressure values occurred. Enalapril showed the most significant reduction of diastolic values above 100 mmHg and the lowest number of diastolic values below 80 mmHg, but the highest number of prescription of diuretics was necessary in the Enalapril group. In none of the four therapy groups a neutralisation of circadian blood pressure rhythmics was demonstrable.
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PMID:[Ambulatory continuous 24-hour blood pressure monitoring in the diagnosis and therapy of arterial hypertension and modification by the antihypertensive agents enalapril, metoprolol, mepindolol and nitrendipine]. 284 47

Optimization of antihypertensive drug therapy continues to be a clinical challenge in patients with diabetes mellitus and its complications. We assessed the interference of autonomic neuropathy with drug effects on heart rate variability in 13 hypertensive diabetic subjects (mean age 48.4 years) during treatment with two blood pressure lowering drugs, metoprolol and enalapril. The baseline findings were compared with those obtained in 24 diabetic subjects without hypertension (mean age 32.5 years) and in 24 non-diabetic hypertensive patients (mean age 47.6 years). Cardiovagal autonomic neuropathy was present in 10/13 (77%) of the hypertensive diabetic group, 14/24 (58%) the non-hypertensive diabetic group and 17/24 (71%) the non-diabetic hypertensive group. Heart rate variation was studied by power spectral analysis using total variability and three different frequency bands (low-frequency 0.025-0.075 Hz, mid-frequency 0.075-0.15 Hz and high-frequency 0.15-0.40 Hz). At baseline, the two hypertensive groups showed significantly smaller mid- and high-frequency heart rate variability compared with the diabetes only group. Age and the presence of cardiovagal autonomic neuropathy were important determinants of variability. Both metoprolol and enalapril reduced blood pressure comparably in hypertensive diabetics while metoprolol also reduced heart rate. Metoprolol decreased heart rate variability at the low-frequency and mid-frequency bands even after correction for the change in heart rate. Heart rate variability was not significantly altered by enalapril. In subjects with hypertension, diabetes and autonomic neuropathy, metoprolol almost abolished all heart rate variability. Therefore, an ACE inhibitor is a more neutral treatment alternative in such patients from the point of view of autonomic cardiac control.
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PMID:Antihypertensive treatment and heart rate variability in diabetic patients: role of cardiac autonomic neuropathy. 888 97

Recently, several randomised controlled studies have demonstrated improvement in survival of patients with non ischemic cardiomyopathy (Bisoprolol, Metoprolol, Carvedilol) and ischemic cardiomyopathy (Carvedilol). It is not quite clear, whether the observed difference in mortality after beta-blockade on top of diuretics, digitalis and ACE-inhibitors is due to some as yet unknown pathophysiological changes. Certainly, beta-blocking agents have an established efficacy in arrhythmia. Irrespective of the acknowledged benefit in survival, one should note, that the risk reduction in mortality by 65% by Carvedilol has to be viewed critically-as the risk reductions in several other large scale trials. If the mortality in the group receiving digitalis, diuretics and ACE-inhibitors was 7.8%, the mortality after addition of Carvedilol was 3.2%. This means a difference of 4.6%. If however, percent from percent is calculated, than the risk reduction amounts to 65%. One can easily understand, why this larger latter, number usually is being published.
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PMID:[Beta-blockers and heart failure--a critical view]. 908 82

There is now considerable clinical trial data to support the use of beta-blockers in patients with congestive heart failure (CHF) due to systolic left ventricular dysfunction. A substantial database has accumulated over the last 20 years supporting the benefits of these agents on ventricular function and clinical status. In addition, morbidity and mortality benefits have been suggested, specifically with the non-selective vasodilating agent, carvedilol. More recently, a "new wave" of clinical trials have been conducted to definitively determine the mortality benefits of beta-blockers in patients with mild to moderate CHF as well as addressing other important clinical questions. These questions include whether the beneficial effects of carvedilol on survival can be reproduced by other agents in prospective, adequately powered studies; whether the benefits of carvedilol in systolic heart failure are due to its beta-blocking properties alone or to a combination of the beta-blocking and ancillary effects of the drug; whether beta-blockers are of benefit in patients with severe New York Heart Association (NYHA) Class IIIB-IV CHF; and, whether beta-blockers are of benefit (additional to ACE inhibitors) in patients with evidence of systolic ventricular dysfunction when commenced in the immediate post-myocardial infarction period. Major studies are currently being undertaken to address the above questions. Most are still underway but 3 studies have recently reported their results: the second Cardiac Insufficiency Bisoprolol Study (CIBIS II), the Research in Left Ventricular Dysfunction Study (RESOLVD), and the Metoprolol CR/XL Randomised Intervention Trial in Heart Failure (MERIT-HF) study. These studies have demonstrated that blockade with beta1-selective, non-vasodilating agents (i.e. bisoprolol and metoprolol) improve survival in patients with CHE Comparison of relative risk reduction in these recent studies with the earlier carvedilol studies raises mechanistic questions, specifically whether non-selectivity, vasodilation and other ancillary properties of carvedilol are critical to its benefit in CHF patients. This question is currently being addressed in the Carvedilol and Metoprolol European Trial (COMET), comparing metoprolol with carvedilol. The beneficial effects of beta-blockers on mortality in patients with mild to moderate CHF have also had major implications in ongoing studies of other agents in this condition. Open-label prescribing of beta-blockers is increasing in these studies and this is having an impact on event rates and thus required duration of administration of study drug. Furthermore, it would now appear unethical to deprive suitable NYHA Class II-III CHF patients of beta-blockers as part of the design of such studies. In conclusion, beta-blockers have now become the most extensively studied class of agents in the treatment of CHF, with a database of over 6000 patients in placebo-controlled studies, and ongoing clinical and mechanistic studies. Despite this, further questions remain regarding the use of these agents in CHF, including their role in the extreme elderly, in patients with diabetes mellitus and in patients with renal impairment.
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PMID:Beta-blockers in heart failure. The 'new wave' of clinical trials. 1047 16

Regional left ventricular contractility caused by myocardial stunning as a result of transient ischemia and postreperfusion injury is a reversible state it can however persist even for several month. It seems reasonable to shorten this period as much as possible. The aim of the study was to estimate the influence of treatment with metoprolol or enalapril on the recovery of contractile function of left ventricle in patients after acute myocardial infarction treated thrombolytically. Investigations were carried out in 127 patients (mean age 62.3 +/- 11.9 years). Metoprolol was used in 37 patients in dose 0.02-0.05 g b.i.d., enalapril in 48 patients 0.0025-0.01 g b.i.d. 42 patients were not treated with any beta-blocker or ACE inhibitor. In all patients echocardiographic study was performed 3 times: on 2-3rd day following acute myocardial infarction immediately before introducing the treatment with metoprolol or enalapril, after 1 month and after 3 months. Echocardiographic study wall motion index (WMI) was calculated basing on. Significant decrease in WMI was observed after 1 month compared to its value on 2-3rd day acute myocardial infarction and after 3 months compared to 1 month after myocardial infarction in each of 3 subgroups of patients. No statistically significant differences in WMI were found out between studied subgroups. Neither metoprolol nor enalapril started on 2-3rd after thrombolytic treatment of acute myocardial infarction do not affect the recovery of contractile function of stunned myocardium.
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PMID:[Influence of treatment with metoprolol or enalapril on recovery of contractile function of the left ventricle in patients after acute myocardial infarction treated by thrombolytics]. 1052 15

Carvedilol is a beta-blocker with ancillary properties. Pilot clinical studies with carvedilol, added to the standard therapy of digoxin, diuretics and ACE inhibitors, showed beneficial effects in mild, moderate and severe heart failure. Patients consistently showed improvement in LV ejection fraction and NYHA functional class. Subsequently large clinical trials showed decreased morbidity and mortality with carvedilol in mild and moderate and more recently, severe heart failure. However, there is little or no improvement in exercise tolerance with carvedilol. The beneficial effects of carvedilol in heart failure are associated with cardiac remodelling. Metoprolol and bisoprolol are selective beta(1)-blockers without ancillary properties. Early studies showed benefits with metoprolol and bisoprolol in heart failure. Large clinical trials established that metoprolol and bisoprolol decreased mortality and morbidity in heart failure. In contrast no benefit has been shown with celiprolol, a selective beta(1)-blocker and beta(2)-stimulant in heart failure. There is a debate as to whether the ancillary properties of carvedilol contribute to its beneficial effect in heart failure, making it a better drug to use than metoprolol. Short-term studies suggested that carvedilol and metoprolol were equivalent in heart failure but short-term is probably not an appropriate way to compare the drugs. A recent long-term study and study in poor responders to metoprolol, suggest that carvedilol may be better than metoprolol in heart failure.
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PMID:Carvedilol versus other beta-blockers in heart failure. 1132 70

Nearly all type 2 diabetic patients are suffering from arterial hypertension. The latter usually becomes manifest earlier than the diabetic metabolic disturbances. Adequate treatment often requires a combination of angiotensin converting enzyme(ACE)-inhibitors and beta-adrenoceptor antagonists. Metoprolol is still the most frequently used beta-adrenoceptor antagonist in this setting. Some clinical trials have shown carvedilol to be superior in improving the metabolic situation and prevention of secondary disorders caused by diabetes. Therefore carvedilol may be the beta-adrenoceptor antagonist of choice for treatment of patients at high cardiovascular risk and especially for diabetes type 2. As comparisons to metoprolol succinate as well as to optimally dosed metoprolol tartrate are missing, a definite superiority of carvedilol cannot be assumed.
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PMID:[Beta-adrenoceptor antagonists and ACE-inhibitors. Carvedilol compared with metoprolol as combination partner in cases of diabetes and hypertension]. 1795 97

There is strong evidence for the use of angiotensin converting enzyme inhibitors and beta-blockers to reduce morbidity and mortality in patients with myocardial infarction (MI), whereas the effect of angiotensin receptor blockers is less clear. We evaluated the effects of an angiotensin receptor blocker losartan and a beta-blocker metoprolol on left ventricular (LV) remodeling, c-kit+ cells, proliferation, fibrosis, apoptosis, and angiogenesis using a model of coronary ligation in rats. Metoprolol treatment for 2 weeks improved LV systolic function. In contrast, losartan triggered deleterious structural remodeling and functional deterioration of LV systolic function, ejection fraction being 41% and fractional shortening 47% lower in losartan group than in controls 2 weeks after MI. The number of c-kit+ cells as well as expression of Ki-67 was increased by metoprolol. Losartan-induced thinning of the anterior wall and ventricular dilation were associated with increased apoptosis and fibrosis, while losartan had no effect on the expression of c-kit or Ki-67. Metoprolol or losartan had no effect on microvessel density. These results demonstrate that beta-blocker treatment attenuated adverse remodeling via c-kit+ cells and proliferation, whereas angiotensin receptor blocker-induced worsening of LV systolic function was associated with increased apoptosis and fibrosis in the peri-infarct region.
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PMID:Divergent effects of losartan and metoprolol on cardiac remodeling, c-kit+ cells, proliferation and apoptosis in the left ventricle after myocardial infarction. 2044 34