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)

Angiotensin receptor antagonists (ARB) are equally effective but better tolerated than all the other blood pressure lowering agents. The reason, why they are not subscribed as first line drugs for uncomplicated hypertension, is the higher price for these products. What the real difference in costs is, remains unclear because calculations are missing to what extent lesser controls of therapy would shift the balance in favour of the ARBs. For other indications than hypertension, but often associated with that condition, be it per se or as a consequence of it, the effects of the ARBs are studied in large trials these days. For some of them the benefit, which has been proven for ACE inhibitors, is not yet established for the ARBs, but evidence emerges that they are also useful in the treatment of cardiac failure, left ventricular hypertrophy and diabetic and other kinds of nephropathy. A large percentage of hypertensive patients can be treated effectively with ARBs without considerable side effects, thus increasing adherence and minimizing the necessity of safety controls.
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PMID:[Angiotensin receptor blockers--significance for the therapy of hypertension]. 1145 Jan 62

Angiotensin (Ang) receptor blockers (ARBs) increase bradykinin (BK) by antagonizing Ang II at its type 1 (AT(1)) receptors and diverting Ang II to its counterregulatory type 2 (AT(2)) receptors. Because the effect of ARBs on BK is constrained by the short half-life of BK and because ACE inhibitors block the degradation of BK, this study was designed to test the hypothesis that an ACE inhibitor can potentiate ARB-induced increases in renal interstitial fluid (RIF) BK levels. We used a microdialysis technique to recover BK and cGMP in vivo from the RIF of sodium-depleted, conscious Sprague-Dawley rats infused for 60 minutes with the AT(1) receptor blocker valsartan (0.17 mg/kg per minute), with the active metabolite of the ACE inhibitor benazepril (benazeprilate, 0.05 mg/kg per minute), or with the specific AT(2) receptor blocker PD 123,319 (50 microg/kg per minute) alone or combined. Each animal served as its own control. RIF BK and cGMP levels increased significantly over 1 hour in response to valsartan, benazeprilate, or both but not to a vehicle control (P<0.01). The combined benazeprilate-valsartan effect was greater than the sum of their individual effects, suggesting potentiation rather than addition, and was abolished by PD 123,319. We demonstrate for the first time that an ACE inhibitor (benazepril) and an ARB (valsartan) potentiate each other, and we postulate that such combinations may be beneficial in clinical states marked by Ang II elevation, such as chronic heart failure, postinfarction left ventricular dysfunction, and hypertension.
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PMID:Angiotensin-converting enzyme inhibition potentiates angiotensin II type 1 receptor effects on renal bradykinin and cGMP. 1150 73

1. ACE inhibitors are indicated for Class I-IV HF due to LVSD. 2. ARBs are recommended for HF patients with contra-indications or intolerance to ACE inhibitors. 3. Spironolactone provides additional benefit for Class IV HF patients. 4. Beta-blockers (carvedilol or long-acting metoprolol) are indicated as additive treatment to an ACE inhibitor or ARB for Class II or III HF. 5. The beta-blocker carvedilol has been found to be safe and effective in patients with severe HF and appears to improve clinical outcomes in patients with LVSD post-MI.
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PMID:Current guidelines in heart failure management. 1191 16

This study evaluated a strategy to treat naive hypertensive patients, based on a single monotherapy followed, in uncontrolled patients, by a rationale choice for the second antihypertensive treatment. Subjects with essential hypertension, entered into the study if their BP measured with an OMRON 705CP was > 140/90 mmHg on two separate visits. Patients were allocated to single treatment in a balanced randomized design to receive either a "group 1" treatment (ACE inhibitor, beta-blocking drug or ARB) or a "group 2" treatment (calcium channel-blocking drug or thiazide diuretic). After one month of treatment at a standard dose, if BP was > 140/90 mmHg, first adaptation was a fixed combination therapy with one drug from "group 1" and one drug from "group 2". At 3 months, patients with BP < 140/90 mmHg were considered to have reached BP goal. Forty-eight patients entered the study with a mean age of 53 +/- 11 years. Initial SBP/DBP (mmHg) was 164 +/- 16/97 +/- 8. After 1 month, 40% achieved the target BP, 52% were uncontrolled with no side effects and 8% were uncontrolled and had side effects. After 3 months, 84% achieved BP goal and a fixed combination therapy was prescribed in 52% of the controlled patients. The initial monotherapy was maintained alone or in combination in 70% of the controlled patients. A strategy based on a single monotherapy followed, if necessary, by a rational choice for the second treatment in a fixed combination therapy is effective to achieve BP control in 84% of naive hypertensive patients.
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PMID:[Rational choice for second antihypertensive agent after failure of the first monotherapy: therapeutic strategy]. 1236 87

Due to therapy resistant hypertension, combination antihypertensive therapy is indispensable for retarding the progression of chronic renal diseases. The majority of pilot studies investigating the renoprotective effect of ACE-I plus ARB revealed a better anti-proteinuric effect of this combination than either of the monotherapies for patients with either diabetic or non-diabetic renal diseases. In contrast, the effect of combination therapy with ACE-I/ARB plus CCB in protecting the kidney from hypertension appeared to be still a matter of controversy. Although the combined therapy with ACE-I plus ARB is superior to that with CCB plus ARB to achieve a greater reduction in urinary protein excretion than either of the monotherapies, one must be aware of the potential hazards associated with the former combined therapy such as worsening of renal anemia and hyperkalemia, especially in patients with impaired renal function. Whether add-on ARB to ACE-I or CCB causes antiproteinuric effects or long-term renoprotection requires larger and longer prospective, randomized controlled trials in the future.
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PMID:[A clinical evaluation on the combination therapy with ACE-I and ARB, and with ARB and CCB in patients with progressive chronic renal diseases]. 1239

Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II (Ang II), AT(1)-receptor blockers (ARB) is the cornerstone of renoprotective therapy. Still, the number of patients with end-stage renal disease is increasing worldwide, prompting the search for improved renoprotective strategies. In spite of proven efficacy at group level, the long-term renoprotective effect of RAAS blockade displays a marked between-patient heterogeneity, which is closely linked to between-patient differences in the intermediate parameters of blood pressure, proteinuria and renal haemodynamics. Of note, the between-patient differences by far exceed the between-regimen differences, and thus may provide a novel target for exploration and intervention. The responsiveness to RAAS blockade appears to be an individual characteristic as demonstrated by studies applying a rotation-schedule design. The type and severity of renal disease, obesity, insulin-resistance, glycaemic control, and genetic factors may all be involved in individual differences in responsiveness, as well as dietary factors, such as dietary sodium and protein intake. Several strategies, such as dietary sodium restriction and diuretic therapy, dose-titration for proteinuria, and dual RAAS blockade with ACE-I and ARB, can improve the response to therapy at a group level. However, when analysed for their effect in individuals, it appears that these measures do not allow poor responders to catch up with the good responders, i.e. in spite of their efficacy at group level, the available measures are usually not sufficient to overcome individual resistance to RAAS blockade. We conclude that between-patient differences in responsiveness to renoprotective intervention should get specific attention as a target for intervention. Unravelling of the underlying mechanisms may allow development of specific intervention. Based on the currently available data, we propose that response-based treatment schedules, with a multidrug approach titrated and adapted at individual responses rather than fixed treatment schedules, may provide a fruitful strategy for more effective renoprotection.
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PMID:Between-patient differences in the renal response to renin-angiotensin system intervention: clue to optimising renoprotective therapy? 1258 64

Although the angiotensin receptor antagonist (ARB) shares the angiotensin-II-blocking activity with the angiotensin-converting enzyme inhibitor (ACE-I), pharmacological mechanisms of action of these agents differ. We evaluated the temporal profiles of action of ACE-I and ARB on urinary protein excretion and nitrate/nitrate (NO(x)) excretion in hypertensive (140 and/or 90 mmHg) patients with chronic renal disease (serum creatinine < 265 (range, 44-265) micromol/l or creatinine clearance > 30 (range, 30-121) ml/min). Patients with mild (<1 g/day; range, 0.4-1.0) and moderate proteinuria (>1 g/day; range, 1.1-6.9) were randomly assigned to ACE-I- and ARB-treated groups, and were treated with ACE-I (trandolapril or perindopril) or ARB(losartan or candesartan) for 48 weeks. In all groups, treatment with ACE-I or ARB decreased blood pressure to the same level, but had no effect on creatinine clearance. In patients with mild proteinuria, neither ACE-I nor ARB altered urinary protein excretion. In patients with moderate proteinuria, ACE-I caused 44 +/- 6% reduction in proteinuria (from 2.7 +/- 0.5 to 1.5 +/- 0.4 g/day, n = 14) at 12 weeks, and this beneficial effect persisted throughout the protocol (48 weeks, 1.2 +/- 0.2 g/day). In contrast, ARB did not produce a significant decrease in proteinuria at 12 weeks (23 +/- 8%, n = 13), but a 41 +/- 6% reduction in proteinuria was observed at 48 weeks. Similarly, although early (12 weeks) increases in urinary NO(x) excretion were observed with ACE-I (from 257 +/- 70 to 1111 +/- 160 micromol/day) and ARB (from 280 +/- 82 to 723 +/- 86 micromol/day), the ARB-induced increase in NO(x) excretion was smaller than that by ACE-I (P < 0.05). In conclusion, although both ACE-I and ARB reduce blood pressure similarly, the effect of these agents on proteinuria differs in chronic renal disease with moderate proteinuria. Relatively early onset of the proteinuria-reducing effect was observed with ACE-I, which paralleled the increase in urinary NO(x) excretion. Conversely, ARB decreased proteinuria and increased urinary NO(x) excretion gradually. These time course-dependent changes in proteinuria and urinary NO(x) may reflect the pharmacological property of ACE-I and ARB, with regard to the action on bradykinin.
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PMID:Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease. 1269 72

ACE inhibitors have been shown to reduce mortality, reduce hospitalization, reduce symptoms, and increase exercise capacity in patients with heart failure and a large heart (low ejection fraction). The evidence is overwhelming. There are some subgroups of patients, such as the very elderly and those with a normal ejection fraction, where uncertainty still exists. The combination of a diuretic and an ACE inhibitor is currently the proper treatment of congestive heart failure; a beta-blocker should be added in selected patients. The evidence for the efficacy of ARB is less persuasive and, for the present, this class of drug should be prescribed only when an ACE inhibitor cannot be tolerated. The results of the trials emphasize an emerging problem in medicine, namely how to evaluate a new treatment that may be as efficacious as current therapy but with fewer side-effects. Proving equivalence in efficacy will be difficult, requiring large studies comparing new drugs with the best current treatment. The most common etiology of heart failure is coronary heart disease. If further studies provide more support for the idea that ACE inhibitors prevent ischemic episodes and delay the onset of heart failure, then a new indication for ACE inhibitors will be the prevention of heart failure.
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PMID:ACE inhibitors and ARBs in chronic heart failure: the established, the expected, and the pragmatic. 1269 30

The issue of how far blood pressure (BP) should be lowered to achieve the greatest reduction in the risk of cardiovascular disease has been a matter of scientific debate. Although a few trials tried to answer this question, they failed to convincingly show the optimal target BP level, in part because of poor reproducibility and wide variability of conventional casual BP measurement used in these trials. On the other hand, in Japan, calcium antagonist (Ca-A) and angiotensin converting enzyme inhibitor (ACE-I) have been two major medications of initial therapy for hypertension, while angiotensin II receptor antagonist (ARB), which has recently been introduced, is also used now widely as an initial therapy. However, no large-scale interventional trial has been conducted to show which of these three initial medication can give the greatest benefit in terms of reduced cardiovascular disease risk in the Japanese hypertensive patients.
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PMID:Study design of HOMED-BP: hypertension objective treatment based on measurement by electrical devices of blood pressure. 1271 76

Women are underrepresented in clinical trials. Lower doses of beta-blockers are required for Southeast Asians. ACE and ARB's are teratogenic in the second trimester. Torsades de Pointes is more common in women related to a longer QT-interval. Lower dose OCPs decrease the risk of MI, stroke and thrombosis. HRTs are not effective for CAD prevention.
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PMID:Gender, ethnicity, and genes in cardiovascular disease. Part 2: implications for pharmacotherapy. 1278 34


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