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)

Large Arteriovenous Fistulae (AVF) can increase cardiac output. This may result in the development of congestive heart failure, a clinical situation associated with increased activity of Vasoconstrictor neurohormonal systems: the Renin-angiotensin system (RAS), Sympathetic nervous system (SNS), the Endothelin system and Arginine vasopressin (AVP). At the same time there is compensatory activation of systemic and vasodilating systems: Atrial natriuretic peptide (ANP) and Nitric oxide (NO). Previous data from our laboratory and other groups suggest that urinary sodium excretion in this situation is largely determined by the balance between two antagonistic hormonal systems: the vasoconstrictor/sodium-retaining factors such as RAS, endothelin, and SNS, and vasodilatory/natriuretic substances such as ANP and NO. In decompensated patients, enhanced activities of the sodium-retaining systems overwhelm the effects of vasodilatory/natriuretic systems, which lead to a net reduction in sodium and water excretion. For compensation to occur, the effects of natriuretic mechanisms must prevail over those of the opposing systems, resulting in renal sodium/water excretion. This notion is supported by clinical and experimental studies where pharmacological intervention corrected the imbalance present in AVF. Thus, a shift in the balance in favor of natriuresis may be achieved either by increasing the activity of natriuretic factors or reducing the influence of the antinatriuretic systems. Based on that, the use of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II (ATII) blockers may be beneficial in the management of patients with large AVF.
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PMID:Large A-V fistula: pathophysiological consequences and therapeutic perspectives. 1532 Apr 81

Activity of the renin-angiotensin-aldosterone system (RAAS) is increased in patients with heart failure, and its maladaptive mechanisms may lead to adverse effects such as cardiac remodelling and sympathetic activation. Elevated renin activity has been demonstrated in patients with dilated cardiomyopathy. (Third- generation synthetic non-peptide renin inhibitors, with more favourable properties than earlier renin inhibitors, lower ambulatory blood pressure and may have a role to play in other cardiovascular disease.) Chymase, a protease inhibitor stored in mast cells that generates angiotensin II (Ang II) (in addition to angiotensin-converting enzyme [ACE]), has been linked to extracellular matrix remodelling in heart failure. Again, chymase inhibitors have been developed to investigate its functions in vitro and in vivo . Bradykinin is thought to contribute to the cardioprotective effect of ACE inhibition through modification of nitric oxide release, calcium handling and collagen accumulation. Ang II is believed to influence a number of molecular and structural changes in the heart, mostly mediated through the AT1-receptor. The importance of the RAAS in heart failure is shown by the survival benefit conferred by treatment with ACE inhibitors.
J Renin Angiotensin Aldosterone Syst 2004 Sep
PMID:The role of the renin-angiotensin-aldosterone system in heart failure. 1552 42

Angiotensin II (AII), the main effector of the Renin Angiotensin System (RAS), plays a central role in the hemodynamic and non-hemodynamic mechanisms of chronic renal disease and is currently the main target of interventions aimed to prevent the onset and progression of chronic nephropathies to end stage renal disease (ESRD). In addition to ameliorate glomerular hyperfiltration and size-selectivity, reduce protein traffic and prevent glomerular and tubulo-interstitial toxicity of ultrafiltered proteins, RAS inhibitors also limit the direct nephrotoxic effects of AII. Thus, both ACE inhibitors (ACEi) and AII antagonists (ATA) exert a specific nephroprotective effect in both experimental and human chronic renal disease. This effect is time-dependent and is observed across degrees of renal insufficiency. Forced ACEi or ATA up-titration above doses recommended to control arterial hypertension and combined treatment with both agents allow to optimise A II inhibition and maximize renoprotection. Multifactorial interventions combining RAS inhibition to treatments targeted also to non-RAS mechanisms may even achieve regression of glomerulosclerosis and chronic tubulo-interstitial injury. Studies are needed to assess whether renal damage can be reverted to such a point that renal function may be fully prevented from worsen, and possibly improve. The economic impact of even a partial improvement would be enormous. Moreover, chronic renal insufficiency is an independent risk factor for cardiovascular disease and effective nephroprotection may also decrease the excess cardiovascular morbidity and mortality associated with chronic nephropathies. In patients with renal insufficiency ACEi are even more cardioprotective than in those without, and are well tolerated. Thus, RAS inhibitor therapy should be offered to all renal patients without specific contraindications, including those closer to renal replacement therapy.
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PMID:Methods of cardio-renal protection in non-diabetic chronic nephropathies. 1563 26

Renin-angiotensin system activation is recognized to play an important role in atherosclerosis. This study aimed to verify the antiatherosclerotic effects of ACE inhibition on an experimental model of diabetes and hypercholesterolemia. Diabetes was induced in New Zealand male rabbits with a single dose of alloxan (100 mg/kg, i.v.), and, according to plasma glucose levels obtained after 1 week, the animals were divided into 2 groups (> or =250 mg/dL or <250 mg/dL). Each group was randomly assigned to receive or not quinapril (30 mg/d) added to a 0.5% cholesterol-enriched diet. Animals with high glucose levels at 1 week and that remained high after 12 weeks presented higher triglyceride levels (P < 0.02 versus basal). Those initially hyperglycemic but presenting <250 mg/dL glucose at the end of study formed an additional group. Plasma ACE activity was lower in quinapril-treated animals (P < 0.01 versus untreated groups). However, aorta intima/media ratio and intima area were lower only in the subgroups of quinapril-treated animals with low glucose levels (P < 0.05). Our results support the hypothesis that high plasma glucose may abolish the antiatherosclerotic effect of ACE inhibitors.
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PMID:High glucose levels abolish antiatherosclerotic benefits of ACE inhibition in alloxan-induced diabetes in rabbits. 1577 16

Atrial fibrillation is the most common disorder of cardiac rhythm. In spite of diagnosis simplicity, patients with atrial fibrillation are difficult to treat. In the recent years with the description of the phenomenon called remodelling, it has been possible to better define the principle mechanisms responsible for initiation, maintenance and, in some instances, termination of atrial fibrillation. Electrical, mechanical and anatomical remodelling indicate those alterations that, once established, may vanish any attempt to restore sinus rhythm. Atrial fibrosis is probably the most critical component of the remodelling process and appears to be largely mediated by the activation of the Renin-Angiotensin-Aldosterone System. Both experimental and clinical data have confirmed the pro-arrhythmic role of the Renin-Angiotensin-Aldosterone System and demonstrated an anti-arrhythmic effects of ACE-inhibitors and AT(1) receptor blockers. Regarding atrial fibrillation, it has been recently reported that the adjunction of AT(1) receptor blocker to amiodarone was more effective than the anti-arrhythmic drug alone, in reducing arrhythmia recurrence after electrical cardioversion. This and subsequent clinical observations indicate that pharmacological interventions capable of interfering with the electrical and structural remodelling process are of critical importance in the management of patients with atrial fibrillation. ACE inhibitors and AT(1) receptor blockers represent new and efficient therapeutical options to contrast the nearly inevitable progression of this arrhythmia towards its permanent form.
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PMID:Renin-angiotensin system block and atrial fibrillation. 1597

We have investigated the frequencies of seven markers among 100 unrelated individuals with angiographically documented CAD (Coronary Artery Disease) and among 100 unrelated healthy blood donors in the central region of Corsica island (France). The seven polymorphisms analyzed were chosen from six candidate genes involved in (1) Renin-Angiotensin system: Angiotensin converting enzyme (ACE I/D), (2) Lipid metabolism: Cholesterol Ester Transfer Protein gene (CETP TAQ1B), (3) Platelet aggregation: alpha and beta subunits of the platelet GpIIb/GpIIIa integrin complex (GpIIb HPA3 and GpIIIa Pl(A1/A2)), (4) Coagulation fibrinolysis: Plasminogen Activator Tissue (PLAT TPA25 I/D) and Methylenetetrahydrofolate Reductase (MTHFR C677T and A1298C). The samples were genotyped using the polymerase chain reaction followed by restriction enzyme analysis for the RFLPs. No significant difference in allele frequencies between patient and control groups was observed. The occurrence of the MTHFR T677T genotype and of the T677T/A1298A compound genotype is higher in cases (20%) than in the controls (4%). Odds ratio seems to indicate that individuals with the MTHFR T677T genotype and the T677T/A1298A compound genotype had a 6-fold increased risk for developing CAD (ORs = 6; 95% CIs = 1.96-18.28) suggesting a possible association of MTHFR C677T with the risk of CAD in Corsican population.
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PMID:Prevalence of genetic risk factors for coronary artery disease in Corsica island (France). 1624 96

Diabetic nephropathy is a major cause of diabetes related morbidity and mortality. The first part of the current review was published in the last issue of this journal and discussed the important role of the renin-angiotensin system (RAS) in diabetic nephropathy and the genetic influence on development of endstage renal disease (ESRD) in diabetic patients. This second part of the review focus on the potential improvement of the current treatment strategy to slow down the loss of kidney function using dual blockade of the RAS with both ACE-inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs). Substantial evidence from short-term studies using surrogate endpoints indicates a beneficial impact of dual blockade of the RAS, not obtainable with single agent blockade alone, both in diabetic and non-diabetic renal disease. This conclusion has been confirmed and extended in a longterm trial with regard to prevention of ESRD in non-diabetic renal disease. Results indicate that dual blockade of the RAS may further slow down, but not arrest progressive loss of renal function. However, studies defining the optimal dose of ACE-I / ARBs without additional adverse effects are essential to ensure relevant comparison with dual blockade therapy. Trials using primary renal endpoints in diabetic nephropathy are still needed, and will finally establish the role of dual blockade of the RAS in a clinical setting.
J Renin Angiotensin Aldosterone Syst 2005 Sep
PMID:Preventing end-stage renal disease in diabetic patients - dual blockade of the renin-angiotensin system (Part II). 1647 Apr 84

Activation of the renin-angiotensin system (RAS) in diabetes is thought to contribute to nephropathy. This is suggested by findings of an enhanced renovascular (RPF) response to RAS blockade with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs). An alternative approach to assess RAS activation is the evaluation of renin release following RAS blockade. Forty-four consecutively enrolled Type 1 diabetic patients (28.2+/-1.5 years) and 37 normal subjects (37+/-2.6 years) in high salt balance were given 25 mg of captopril and 16 mg of candesartan p.o. on consecutive days. All subjects were Caucasian. All, except one diabetic patient, had normal renal function. Plasma renin activity (PRA) and renal plasma flow (RPF) were measured for four hours after both drugs, and at eight, and 24 hours after candesartan. As anticipated, both drugs increased PRA. Peak responses (90' after captopril) were 5.6+/-1 ng/mL Ang I/hour in diabetic patients, and 1.7+/-0.9 ng/mL Ang I/hour in normal subjects (p<0.001). Responses to both drugs were correlated in diabetic patients for PRA (r=0.623; p=0.001) and for RPF (r=0.9; p<0.001). When the PRA response to captopril was below the median, the RPF response was limited (22.1+/-17.6 ml/minute/1.73 m2). When it was above the median, the RPF response was also larger (62.2+/-13.9 ml/minute/1.73 m2; p=0.006). Renin response to ACE-I and ARB confirms activation of the RAS in diabetic patients.
J Renin Angiotensin Aldosterone Syst 2005 Sep
PMID:Renin release in response to Renin system blockade: activation of the Renin system in type 1 diabetes mellitus. 1647 Apr 86

Angiotensin-converting enzyme inhibitors (ACE-I) reduce proteinuria and protect the kidney in proteinuric renal disease. During ACE-I therapy, circulating levels of angiotensin (1-7) [Ang (1-7)] are increased. As cardiac and renal protective effects of Ang (1-7) have been reported, we questioned whether Ang (1-7) contributes to the anti-proteinuric effects of ACE-I treatment. Therefore, we evaluated whether Ang (1-7) infusion reduces proteinuria in a rat model of adriamycin-induced renal disease. In addition, the effect of a selective Ang (1-7) blocker, [D-Ala7]-Ang (1-7) (A779), was investigated in rats treated with the ACE-I, lisinopril (LIS). Six weeks after induction of proteinuria, therapy was started in four different groups: control, Ang (1-7), LIS, and LIS+A779. After two weeks, the rats were sacrificed. Six weeks after injection of adriamycin, the rats had developed proteinuria of 323+/-40 mg/24 hours. The proteinuria remained stable in the control group and in the Ang (1-7) group, but was reduced in both LIS and LIS+A779-treated groups. Similarly, blood pressure (BP) was unchanged in the control and the Ang (1-7) groups, but reduced in both the LIS and the LIS+A779 groups. Plasma levels of Ang (1-7) were increased in the Ang (1-7) and in both LIS-treated groups. We conclude that systemic Ang (1-7) plays no major role in the anti-proteinuric and BPlowering effects of ACE-I in this rat model of adriamycin-induced nephrosis.
J Renin Angiotensin Aldosterone Syst 2005 Sep
PMID:Does angiotensin (1-7) contribute to the anti-proteinuric effect of ACE-inhibitors. 1647 Apr 89

Angiotensin-converting enzyme inhibitors (ACE-Is) prevent target organ damage in several models of hypertension. The aim of this study was to assess the influence of the ACE-I enalapril (10 mg/kg(-1) per day, gavage) on the cardiovascular alterations and production of free radicals induced by chronic infusion of angiotensin II (Ang II, 200 ng/kg(-1) per minute, s.c.) in Sprague-Dawley rats. Enalapril was given concomitantly for the 10 days of Ang II infusion (prevention) or from day 10 to 17 of Ang II infusion (intervention). The influence of the NADPH oxidase inhibitor apocynin (600 mg/L(-1) in drinking water) was evaluated. Enalapril and apocynin had no effect on hypertension in the prevention and intervention studies. Enalapril prevented the increase in heart weight index (HWI), carotid cross-sectional area (CSA) and albuminuria induced by Ang II. Enalapril reduced HWI and albuminuria whereas CSA was not affected in the intervention study. Apocynin had effects comparable to enalapril. Both enalapril and apocynin reduced the overproduction of superoxide anion by the left ventricle and rise in advanced oxidation protein products induced by Ang II. Therefore, the antioxidant but not the antihypertensive effect of enalapril may participate in the prevention and treatment of the Ang II-induced cardiovascular and renal alterations.
J Renin Angiotensin Aldosterone Syst 2005 Dec
PMID:Prevention and reversal by enalapril of target organ damage in angiotensin II hypertension. 1652 47


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