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)

Recent clinical studies have established an important role of angiotensin converting enzyme inhibitors (ACE-I) as a tool for renal protection. Although angiotensin receptor antagonists (AII-A) share the common property with ACE-I with regard to blockade of angiotensin activity via angiotensin type 1 receptors (AT1), AII-A is also reported to stimulate AT2 that plausibly activates nitric oxide production within renal medulla and augments synthesis of vasodilatory P450-metabolites in renal afferent arterioles. In contrast, AII-A is reported to have no effect on bradykinin activity. Results obtained in experimental animals indicate that AII-A effectively prevents the progression of renal injury. Several clinical studies are in progress, and the preliminary results suggest that AII-A has potent renal protective action in a variety of renal disorders.
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PMID:[Potential role of angiotensin receptor antagonists in renal protection]. 1036 51

Recently, several antagonists of angiotensin II receptors (AII-A) have been developed and are now used as antihypertensive agents. The regional cerebral blood flow appears to show typical changes during the course of cerebral ischemia and AII-A may have a favorable effect on the flow in some situations. Moreover, activation of the renin-angiotensin system plays an important role in the development of cerebrovascular lesions in chronic hypertension. Because several enzymes appear to produce angiotensin II in the absence of classical renin-angiotensin system, it is possible that angiotensin II is produced in some blood vessels even after inhibition of the activity of ACE. Thus, AII-A may be more effective to treat cerebrovascular lesions during hypertension than ACE inhibitors.
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PMID:[Angiotensin II receptor antagonists as the agents to treat cerebrovascular disease]. 1041 76

The main pharmacodynamic difference between angiotensin-converting enzyme-inhibitors (ACE-i) and angiotensin-II-receptor antagonists (AII-r) is that ACE-i increase levels of bradykinin, which, in addition to vasodilation, may cause a decrease in insulin resistance. Hypertensive patients with diabetes type II suffering from side effects from ACE-i are frequently changed over to AII-r. The objectives of this study were (1) to study whether this procedure reduces metabolic control, (2) to study effects on blood pressure and forearm blood flow (FLOW), and (3) to study possible associations between the variables hemoglobin A (1c) (HbA(1c)) and FLOW. A self-controlled sequential comparison is required to address such questions. Sixteen patients were treated with 10 mg enalapril or equipotent doses of other ACE-i for 6 months and subsequently with the AII-r losartan at 50 mg daily for 6 more months. Patients were examined at the outpatient clinic every 4 to 8 weeks during the trial. FLOW was measured by iridium strain gauge venous occlusion plethysmography. Mean arterial pressure (MAP) increased by 4 +/- 5 mm Hg (P <.05) after 6 months of losartan treatment as compared with the point of withdrawal of ACE-i. FLOW decreased by 5.4 +/- 5.0 mL/100 mL tissue/min (P <.001), and HbA (1c) increased by 0.6 +/- 0.8 mmol/L (P <.05). Other metabolic variables, including cholesterol, high-density lipoprotein cholesterol, and triglycerides, were not significantly influenced by the change in therapy. Multiple regression analysis revealed that after adjustment for difference in HbA (1c), the correlation between FLOW and MAP was unchanged, and after adjustment for difference in FLOW, the correlation between HbA (1c) and MAP was no longer significant. Replacement of ACE-i by AII-r in hypertensive patients with type II diabetes mellitus induced a significant increase in HbA (1c) and MAP and a decrease in FLOW. The associations of HbA (1c) and FLOW with MAP were at least partly independent of each other, suggesting that mechanisms other than the bradykinin system (eg, the angiotensin (2) -receptor system) are involved. Our study design did not control for placebo and time effects, and so the data are of a preliminary nature.
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PMID:Replacement of angiotensin-converting enzyme inhibitors by angiotensin-II-receptor antagonists in hypertensive patients with type II diabetes mellitus: metabolic and hemodynamic consequences. 1042 54

Bradykinin (BK) is a potent hepato-portal hypertensive agent although it is efficiently inactivated by the liver. The organ converts angiotensin I to AII, but at a much slower rate than it inactivates BK. We had previously identified EC 3.4.24.15 as an hepatic bradykinin inactivating endopeptidase that hydrolyzes BK at the F5-F6 bond. The aim of this study was to determine the relative importance of BIE, as compared to other kininases, in normal, cirrhotic or inflamed rat livers, as well as in samples of human liver. Using specific substrates and inhibitors we showed that: 1) purified BIE preparation hydrolyzed BK and a BK analogue (BK-Q) with similar efficacy; BK-Q was functionally active since it caused an increase in hepato-portal pressure, as did BK itself. 2) BK degradation in rat serum was performed by ACE since BIE and prolylendopeptidase (PEP) activities were negligible. 3) normal rat liver homogenate contained a large amount of BIE activity which was eliminated by a specific EC 3.4.24.15 inhibitor; ACE and PEP activities were negligible. 4) There was no difference (p>0.05) in BIE activity in the liver homogenates from rats with normal, inflamed or cirrhotic livers. 5) BIE activity was efficiently removed from livers (normal, inflamed or cirrhotic) that were perfused with TritonX-100.6) Human liver had an similar enzymatic pattern although ACE activity was detected. We concluded that in normal, inflamed or cirrhotic rat livers, as well as in the human liver, the bradykinin inactivating endopeptidase (EC 3.4.24.15), and not ACE, is the major hepatic kininase.
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PMID:Thimet oligopeptidase EC 3.4.24.15 is a major liver kininase. 1099 16

The A II antagonists (RA II antagonists) are a new group of anti-hypertensive drugs with five years of clinical use. They were investigated after the knowledge of independent ways to get angiotensin II. They block AT1 receptor. It's possible that, after AT1 block, the high plasmatic levels of AII stimulate the AT2 receptors with vasodilation and anti-proliferative activity. We are waiting for the results of several big prospective studies with RA II antagonists on cardiovascular morbidity and mortality. At present time, the first indication for its use is the appearance of cough when taking ACE inhibitors. The association of ACE inhibitors and RA II antagonists can improve some clinical conditions like dilated hypertensive cardiopathy, nephropathy or refractory hypertension.
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PMID:[ACE inhibitors versus AR II antagonists. Their role in arterial hypertension]. 1130 10

In patients with hypertension and chronic renal parenchymal disease, BP should be controlled to 130/85 mmHg or lower (125/75 mmHg) in patients with proteinuria in excess of 1 g/day. Reducing dietary sodium (< 7 g/day) and protein (< 0.6-0.7 g/kg) helps control high BP and renal function in patients with renal insufficiency. As first antihypertensive drug, ACE inhibitors or long-acting Ca antagonists are recommended. In patients with renovascular hypertension, angioplasty is the first choice increasingly to be accompanied by stenting, and surgical revascularization is the next choice. As antihypertensive drugs, beta blockers, ACE inhibitors, and AII-receptor blockers are recommended. Hypertension accompanied by endocrine disease with adenoma or tumor is almost cured or improved by surgical removal. Spironolactone and Ca antagonists are used in patients with idiopathic aldosteronism (bilateral hyperplasia). Alpha and beta blockers are used in patients with pheochromocytoma during preoperative period.
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PMID:[Secondary hypertension]. 1139 95

The aim of this study was to analyze if the upregulation of angiotensin-converting enzyme and AT1 receptors observed in a model of neointima formation results in increased contractions to angiotensin I (AI) and AII. Endothelial denudation was performed in left common carotid arteries of 3-month-old male Sprague-Dawley rats. Rats were killed at days 0, 4, 8 and 14 after injury and vascular reactivity was assessed in an organ bath. Responses were always compared with their contralateral vessels as a control. Contractile responses to 75 mM KCl were similar between groups. Noradrenaline (0.1 microM) induced significantly higher contractions at days 0 and 4. Relaxation to acetylcholine (Ach) (1 nM to 0.1 mM) was suppressed at day 0 and increased with time after injury. Relaxations to sodium nitroprusside (0.1 nM to 0.1 mM) were similar at all time points studied. Responses to AI and AII were increased at early steps of neointima formation and decreased with time after injury correlating with increased responses to Ach. Concentration-response curves to AI and AII had similar EC50 or Emax values at the same time points. These results indicate that in the rat i) neointima formation does not impair contractile responses to KCl nor relaxation to SNP, ii) a functional endothelium seems to regenerate with time after injury, and iii) the increase in ACE activity and AT1 receptor number does not have functional consequences.
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PMID:The upregulation of angiotensin-converting enzyme during neointima formation does not have functional consequences. 1169 65

ACE-inhibitors (ACE-I) represent effective drugs more and more widely used in acute myocardial infarction (AMI) patients, in post AMI patients and mainly, today, in CHF patients.A complete review of the scientific literature and of all the randomized controlled clinical trials (RCTs), where ACE-I have been tested directly or in association with other drugs, have been performed. ACE-I effects on total mortality (TM) and arrhythmic mortality (AM) and other composite clinical endpoints have been evaluated. It is well known that frequent ventricular arrhythmias (VA) and a high incidence of sudden death (SD) can be documented in CHF patients; nevertheless a direct relationship between VA, TM, and AM has not been clearly demonstrated; neither beneficial effects, on the same endpoints, of the treatment and suppression of ambient VA in CHF. Conversely, sometimes clear negative effects on both TM and AM have been observed. According to individual studies and two recent complete and large metanalysis, ACE-I were unable to reduce AM, but they reduced TM. Furthermore, they can affect and modify many, if not all, of the triggering factors of VA and SD in this context. Differently from ACE-I, betablockers (BB) have been clearly associated with a reduction in TM and AM, in the same context. Thus, at present time, ACE-I, with or without BB, should be considered the standard therapy in all patients with CHF, if not contraindicated. Angiotensin II antagonists (AII-a) probably represent a comparably effective treatment, in all CHF patients and mainly in those patients, suffering from side effects or showing intolerance to ACE-I, but we are still lacking definitive data from RCTs. In many RCTs, conducted with traditional antiarrhythmic drug therapy (ADT), these drugs have been widely used, contributing probably, in a consistent way, to some of the positive results of these studies. All primary and some secondary implantable defibrillators (ICD) RCTs, in the prevention of SD, have included these drugs as the standard treatment of the underlying cardiac disease, with or without CHF. The same therapeutical strategy is regularly applied in all biventricular pacing (BP) RCTs, with or without the ICD. These trials are supposed to assess the reduction in TM and AM, preventing deterioration or progression of CHF and improving the quality of the patients' s life.Finally, according to these clinical evidences, in the last part of the review, we stress the need for a more widespread implementation of ACE-I and AII-a in treating CHF patients.
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PMID:Do ACE inhibitors or angiotensin II antagonists reduce total mortality and arrhythmic mortality? A critical review of controlled clinical trials. 1179 Sep 28

Radiation nephropathy has emerged as a major complication of bone marrow transplantation (BMT) when total body irradiation (TBI) is used as part of the regimen. Classically, radiation nephropathy has been assumed to be inevitable, progressive, and untreatable. However, in the early 1990's, it was demonstrated that experimental radiation nephropathy could be treated with a thiol-containing ACE inhibitor, captopril. Further studies showed that enalapril (a non-thiol ACE inhibitor) was also effective in the treatment of experimental radiation nephropathy, as was an AII receptor antagonist. Studies also showed that ACE inhibitors and AII receptor antagonists were effective in the prophylaxis of radiation nephropathy. Interestingly, other types of antihypertensive drugs were ineffective in prophylaxis, but brief use of a high-salt diet in the immediate post-irradiation period decreased renal injury. A placebo-controlled trial of captopril to prevent BMT nephropathy in adults is now underway. Since excess activity of the renin-angiotensin system (RAS) causes hypertension, and hypertension is a major feature of radiation nephropathy; an explanation for the efficacy of RAS antagonism in the prophylaxis of radiation nephropathy would be that radiation leads to RAS activation. However, current studies favor an alternative explanation, namely that the normal activity of the RAS is deleterious in the presence of radiation injury. On-going studies suggest that efficacy of RAS antagonists may involve interactions with a radiation-induced decrease in renal nitric oxide activity or with radiation-induced tubular cell proliferation. We hypothesize that while prevention (prophylaxis) of radiation nephropathy with ACE inhibitors, AII receptor antagonists, or a high-salt diet work by suppression of the RAS, the efficacy of ACE inhibitors and AII receptor antagonists in treatment of established radiation nephropathy depends on blood pressure control.
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PMID:ACE inhibitors and AII receptor antagonists in the treatment and prevention of bone marrow transplant nephropathy. 1257 Jul 91

In recent years, many national and international organizations have developed clinical practice guidelines for the most important areas of nephrology. In 1999, the Italian Society of Nephrology (SIN) was one of the first scientific societies to publish (in Giornale Italiano di Nefrologia) the Guidelines for the Treatment of Chronic Renal Failure. Since then, new evidence has accumulated on several aspects of the conservative treatment of chronic kidney disease (CKD). These new data have been included in the present version of the guidelines. The first section of the new guidelines underline the importance of the early detection of CKD and early referral to a nephrologist. The second and third sections are dedicated to the dietetic treatment of chronic renal failure, even when associated with nephrotic syndrome. The fourth section analyzes the anti-hypertensive treatment of renal failure, focusing on the choice of anti-hypertensive drugs to retard the progression of renal failure and reduce cardiovascular mortality. This section highlights the reno-protective role of ACE inhibitors and of AII receptor antagonists in diabetic and nondiabetic nephropathies. The Appendix describes methods for the evaluation of the patient's nutritional status and for protein intake in chronic renal failure.
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PMID:[Conservative therapy Guidelines for chronic renal failure]. 1466 3


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