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 aim of our study was to evaluate whether inhibition of ACE (lisinopril 10-20 mg/day) can reduce the rate of decline in kidney function more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg/day), usually in combination with a diuretic. We performed a prospective, randomized, parallel study for 42 months, double blind for the first 12 months and single blind thereafter. Forty-three (21 lisinopril and 22 atenolol) hypertensive NIDDM patients with diabetic nephropathy were enrolled. Data from 36 patients (17 lisinopril and 19 atenolol, 60 +/- 7 years of age, 27 men) who completed at least 12 months of the study period are presented. At baseline, the two groups were comparable: glomerular filtration rate (51Cr-EDTA plasma clearance) was 75 +/- 6 and 74 +/- 8 ml x min(-1) x 1.73 m(-2), mean 24-h ambulatory blood pressure (A&D TM2420) was 110 +/- 3 and 114 +/- 2 mmHg, and 24-h urinary albumin excretion rate was 961 (range 331-5,727) and 1,578 (476-5,806) mg/24 h in the lisinopril and atenolol groups, respectively. The mean follow-up time was similar, 37 and 35 months in the lisinopril and atenolol groups, respectively. Mean ambulatory blood pressure was equally reduced in the two groups, 12 +/- 2 and 10 +/- 2 mmHg in the lisinopril and atenolol groups, respectively. Glomerular filtration rate declined in a biphasic manner with a faster initial (0 to 6 months) change of 1.25 +/- 0.49 and 0.81 +/- 0.29 ml x min(-1) x month(-1) followed by a slower sustained decline (6 to 42 months) of 0.59 +/- 0.10 and 0.54 +/- 0.13 ml x min(-1) x month(-1) in the lisinopril and atenolol groups, respectively. No significant differences were observed in either initial or sustained decline in glomerular filtration rate between the two groups. Urinary albumin excretion was reduced (% reduction of baseline) more in the lisinopril than in the atenolol group, at 55 (95% CI 29-72) and 15% (-13 to 34), respectively (P = 0.01). In conclusion, the relentless decline in kidney function characteristically found in hypertensive NIDDM patients with diabetic nephropathy can be reduced equally effectively by two antihypertensive treatments, the beta-blocker atenolol and the ACE inhibitor lisinopril.
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PMID:Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy. 920 Jun 54

The therapeutic advantage of the long acting ACE-inhibitor benazepril in a 12 weeks intervention period on 23 diabetic (3 IDDM, 20 NIDDM) patients with essential hypertension was studied. Participants-giving informed consent before beginning the study-on the base of repeated casual blood pressure measurements were divided into "slightly" (n = 8) and "moderately" (n = 15) hypertonic groups. Type of diabetes, time elapsed since its manifestation, actual antidiabetic therapy, period of existence of the hypertension (newly discovered vs known and treated for a time) were independent from the point of view of entering the study. Initial dose of benazepril was 5-10 mg/day depending on the blood pressure level, followed by a stepwise dose elevation according to the control investigations (at weeks 2, 4, 8 and 12 casual blood pressure control, at weeks 4 and 12 ambulantory blood pressure monitoring, ABPM as well) to a maximal daily dose of 20 mg. In the majority of patients benazepril was given in a morning single dose, in some cases because of a better tolerability divided into two parts. 20 patients received benazepril in monotherapy, 3 patients combined with other antihypertensive preparations. Parameters indicating severity of hypertension-hypertonic time index, hyperbaric impact-showed significant improvement already at week 4 when analysed in the total of patients and the moderately hypertonic group respectively. As a tendence the same was observed also in the slightly hypertonic group. No remarkable side effects, or alterations of the metabolic state and in the investigated laboratory parameters appeared. Based on these results benazepril is an effective choice in the treatment of diabetic hypertensive patients.
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PMID:[Experience with benazepril, a long-acting ACE inhibitor, in the management of diabetic hypertension]. 927 85

Initiation of antihypertensive treatment in hypertensive non-insulin-dependent diabetic (NIDDM) patients with diabetic nephropathy induces a faster initial (0 to 6 months) and slower subsequent (6 months-end) decline in GFR [delta GFR (ml.min-1.1.73 m-2.month-1) approximately 1.5 vs. 0.4]. Whether this initial phenomenon is reversible (hemodynamic) or irreversible (structural damage) after prolonged antihypertensive treatment is not known. To elucidate these mechanisms we investigated 40 hypertensive NIDDM patients (age 61 +/- 7 years, mean +/- SD), known duration of diabetes 14 years (2 to 33 years) [median (range)] with diabetic nephropathy receiving antihypertensive treatment (angiotensin converting enzyme inhibition, N = 30) for 5 years (1 to 20 years). The following variables were measured the last day on antihypertensive treatment and one month after withdrawal of treatment; GFR (51Cr-EDTA), 24-hour arterial blood pressure (24 hr MABP, Takeda TM2420) and albuminuria (ELISA); the mean 24-hour MABP rose from 102 +/- 11 to 111 +/- 10 (P < 0.0001) and albuminuria [geometric mean (antilog SEM)] increased from 634 (1.3) to 1159 (1.2) (P < 0.0001), while GFR (mean +/- SD) remained unchanged (69 +/- 25 to 70 +/- 26 ml.min-1.1.73 m-2, P = 0.21), after withdrawal of antihypertensive treatment. A significant correlation between the relative change in the 24 hour MABP measurement and the relative change in GFR (r = 0.44, P < 0.01) was found. In conclusion, our results suggest that the faster initial decline in GFR after initiating antihypertensive treatment in hypertensive NIDDM patients with diabetic nephropathy is due to a irreversible effect, and should be accounted for when evaluating the beneficial effect of antihypertensive treatment on the progression of diabetic nephropathy in these patients.
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PMID:Kidney function after withdrawal of long-term antihypertensive treatment in diabetic nephropathy. 940 21

The presence of persistent microalbuminuria in IDDM is strongly predictive of the future development of end stage renal failure and of cardiovascular disease to a lesser extent. Screening for microalbuminuria is an essential component of modern diabetes practice, as effective antihypertensive therapy, and particularly, the use of angiotensin converting enzyme inhibitors is of proven benefit in retarding progression of renal disease. Cost benefit analysis justifies the expense of microalbuminuria screening programmes and early intervention. It has been estimated that the use of angiotensin converting enzyme inhibitors in microalbuminuric IDDM will save 5200 Pounds-11,000 Pounds per year of life saved. Angiotensin converting enzyme inhibitors are not free of side-effects, and it is therefore essential, given the intrinsic variability of the albumin excretion rate, and the regression to normoalbuminuria of a significant proportion of patients, to confirm the diagnosis of microalbuminuria by repeated measurements prior to the commencement of treatment. The value of intensive glycaemic control is unproven, and further prospective studies are required. There are no proven therapies for the prevention of macrovascular disease in IDDM, although the value of cessation of smoking and aggressive blood pressure control are undoubted in the non-diabetic population. Controversy persists about the value of lipid lowering therapy, especially in young patients, although even in this group there is an increased risk of cardiovascular disease. Microalbuminuria is the strongest known predictor of cardiovascular disease in NIDDM; in contrast to the situation in the non-diabetic population, active lipid lowering therapy is not of proven cardiac benefit, but intervention seems justifiable when taken in the context of the very high prevalence of cardiovascular disease. Microalbuminuria is also predictive of end stage renal disease in NIDDM. Although intervention with angiotensin converting enzyme inhibitors has not been proven to prevent end stage renal disease, stabilisation of albumin excretion rate and creatinine clearance have been demonstrated in normotensive NIDDM, and it seems likely that longer term follow-up studies will confirm the benefit of angiotensin converting enzyme inhibitors in the prevention of end-stage renal disease. The observed predictive power of microalbuminuria as regards both cardiac and renal risk in NIDDM when considered in conjunction with the preliminary results of the benefits of angiotensin converting enzyme inhibition lend further support to the employment of microalbuminuria screening in NIDDM.
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PMID:Microalbuminuria: a marker to increased renal and cardiovascular risk in diabetes mellitus. 950 84

In Hungary the use of angiotensin converting enzyme inhibitor enalapril has emerged as one of the most important drugs in the treatment of hypertension. The aim of our study was to evaluate the antihypertensive effect of enalapril of Hungarian production in combination therapy and alone, according to sexes, to the body mass index, among smokers and non smokers as well as non diabetic and in patients with diabetes (IDDM and NIDDM). The diurnal blood pressure values were registered by a 24 hour ambulatory blood pressure monitor. During the 6 weeks of the enalapril therapy (n = 28) both the daytime (141/84 vs. 135/80 mmHg) and the night-time (130/78 vs. 124/72 mmHg) blood pressure values decreased; the increase of diurnal indices during the therapy (SI/DI 6/8% vs. 8/10) reflect the 24 hour long lasting effect of the drug. The body mass index had no influence on the efficacy of treatment. Our results indicate that enalapril manufactured in Hungary is an effective antihypertensive drug both in monotherapy and in combination, in both sexes (especially in men), irrespective of the body weight, in non-smokers and especially in smokers, in insulin dependent and in non-insulin dependent diabetes mellitus alike.
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PMID:[The place of enalapril in the management of hypertension]. 952 25

The prevalence of abnormally elevated albumin excretion rate (> 30 mg/24 h) is approximately 40% in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients. Diabetes has become the leading cause of end-stage renal failure in the US, Japan and Europe. Approximately 90% of the direct and indirect cost of caring for diabetic patients are spent on the complications of diabetes. Identification of patients at high risk of developing diabetic nephropathy is possible by screening for microalbuminuria (30-300 mg/24 h). Elevated urinary albumin excretion rate indicates a substantially increased mortality risk in diabetic patients. Randomised controlled trials in normotensive IDDM and NIDDM patients with persistent microalbuminuria indicate that ACE inhibitors diminish urinary albumin excretion rate, postpone it and may even prevent progression to clinical overt nephropathy. These findings indicate that screening and intervention programs are likely to have life saving effects and lead to considerable economic savings. Systemic blood pressure elevation to a hypertensive level is an early and frequent phenomenon in diabetic nephropathy. Furthermore, nocturnal blood pressure elevation (non-dippers) occurs more frequently in patients with nephropathy. Systemic blood pressure elevation and to a lesser degree albuminuria accelerate the progression of diabetic nephropathy. Effective blood pressure reduction with non-ACE-inhibitors and/or ACE-inhibitors frequently in combination with diuretics: (a) reduces albuminuria; (b) delays the progression of nephropathy; (c) postpones renal insufficiency; and (d) improves survival in IDDM and NIDDM patients with diabetic nephropathy. A specific renal protective effect of ACE-inhibitors in diabetic nephropathy has been demonstrated in IDDM patients with moderately reduced kidney function (s-creatinine > 133 mumol/l) while the data conflict with NIDDM patients. Antihypertensive treatment for diabetic nephropathy simultaneously extends life and saves money. Finally, reduced risk of fatal and non-fatal cardiovascular events have been demonstrated when diabetic patients with isolated systolic hypertension are treated with blood pressure lowering agents. Absolute risk reduction with active treatment compared to placebo was twice as great for the diabetic versus non-diabetic patients (101/1000 versus 51/1000 randomised participants at the 5-year follow-up), reflecting the higher risk of diabetic patients. In conclusion, early detection and aggressive treatment of arterial hypertension with ACE-inhibitors, long acting calcium antagonist and low dose diuretics as first line drugs are highly warranted in diabetic patients with or without diabetic renal disease.
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PMID:Is antihypertensive treatment the same for NIDDM and IDDM patients? 964 59

The aim of the present study was to examine the relationships between ambulatory blood pressure (ABPM) and urinary albumin excretion (UAE) in diabetic (non-insulin dependent [NIDDM] and insulin-dependent [IDDM]) hypertensives at baseline and after treatment by an angiotensin converting enzyme (ACE) inhibitor. After a 3-week placebo period, patients were treated for 16 weeks with trandolapril, 2 to 4 mg/day. The UAE and blood pressure (mercury sphygmomanometer and 24-h ABPM) were measured at baseline and repeated on trandolapril. Predictive factors of abnormal UAE (24-h UAE > or = 30 mg) were determined using univariate and multivariate analysis (logistic regression). Predictors of UAE decrease were also searched. One hundred seventy-one patients entered the analysis. Baseline office BP was 164+/-14 / 97+/-6 mm Hg and 24-h BP was 142+/-17 / 83+/-10 mm Hg. Seventy-four patients (43%) had UAE > or = 30 mg. Independent risk factors for abnormal UAE were nighttime diastolic BP (odds ratio [OR] = 4.1, confidence interval [CI] = 2.0 to 8.6, P = .0001), diabetes duration (OR = 2.4, CI = 1.1 to 5.0, P = .025), and presence of retinopathy (OR = 3.2, CI = 1.0 to 10.0, P = .047). Conversely, office BP level was not significantly related to UAE. On treatment, office BP levels decreased to 143+/-13 / 82+/-8 mm Hg (P < .0001) and 24-h BP levels to 134+/-17 / 78+/-9 mm Hg (P < .0001). In the abnormal UAE group, UAE significantly decreased from 76 to 50 mg/day (P = .006). After treatment, independent predictive factors of abnormal UAE were: on-drug fasting plasma glucose (OR = 3.5, CI = 1.7 to 7.4, P = .0009) and on-drug nighttime diastolic BP (OR = 3.5, CI = 1.7 to 7.4, P = .001). The only predictor of UAE decrease was a 24-h systolic BP decrease (OR = 2.3, CI = 1.3 to 4.3, P = .007). We conclude that in diabetic hypertensives with abnormal UAE, trandolapril exhibited a sustained 24-h antihypertensive effect and provided a consistent reduction of microalbuminuria. This study confirmed the superiority of ABPM over clinical BP to predict target organ damage.
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PMID:Ambulatory blood pressure and urinary albumin excretion in diabetic (non-insulin-dependent and insulin-dependent) hypertensive patients: relationships at baseline and after treatment by the angiotensin converting enzyme inhibitor trandolapril. 975 91

Diabetic nephropathy has become the single most important cause of endstage renal failure in most countries of the Western world. Against this background, the role of the renin-angiotensin system (RAS) and its blockade command considerable interest. In diabetic patients and in diabetic animals, the circulating components of the RAS are suppressed. Although the evidence is not completely uniform, there are indirect arguments (renal hemodynamic response to RAS blockade, AT1 receptor expression), however, which would be consistent with increased intrarenal action of angiotensin (ANG) II. There is solid evidence that ACE inhibitors effectively interfere with progression of micro-albuminuria both in IDDM and NIDDM. They also prevent progression of advanced renal failure in IDDM, while there is only preliminary evidence in this respect for NIDDM. ACE inhibitors are superior to conventional antihypertensive agents (with the possible exception of some calcium channel blockers), but such superiority is seen only when the levels of blood pressure are relatively high. In diabetic animals, treatment with ANG II receptor blockers interferes with the development of glomerular lesions. In acute and subacute studies on diabetic patients, ANG II receptor blockers reduced albuminuria (or proteinuria) more than beta-blockers. Head-on comparison of equipotent doses ACE inhibitors and ANG II receptor blockers in non-diabetic patients produced equal reductions in proteinuria. The long-term effects of ANG II receptor blockers on progression of advanced diabetic nephropathy is the object of two large international studies. The results will not be available before the year 2000.
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PMID:Diabetes--renal function--what are the special problems? 983 74

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

Diabetes is a chronic condition which poses a risk for three major complications. They are diabetic retinopathy, nephropathy and neuropathy. Almost one third of diabetic patients (IDDM or NIDDM) develop diabetic nephropathy in their life time. Because of increased vascular permeability in chronic conditions increased urinary albumin excretion in the range of 30-200 mg/L (microalbuminuria) gives an early signal of incipient diabetic nephropathy. The prevalence of microalbuminuria was found to be 41% in diabetic patients with duration of more than 5 years. Seventy percent of diabetic patients with microalbuminuria were hypertensive. ACE inhibitors are shown to have significant effects on microalbuminuria and hypertension. We conclude that microalbuminuria is an early feature of excessive capillary leakage and its assessment in diabetic patients with duration of more than 5 years provides a simple non-invasive method of early diagnosis of incipient diabetic nephropathy. An early intervention may retard the progression to end-stage renal disease (ESRD).
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PMID:Diabetes, microalbuminuria and hypertension. 1005 42


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