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 actions of des-Asp angiotensin I, a nine aminoacid peptide, on the contractility of the aortic rings of the normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were studied. In the presence of captopril which prevented its degradation to angiotensin III by angiotensin converting enzyme, des-Asp-angiotensin I exerted direct concentration-dependent contractile action on the aortic rings. The contractile action was concentration-dependently attenuated by the AT1 receptor antagonist, losartan, but was not affected by the AT2 receptor antagonist, PD123319; indicating that angiotensin AT1 receptors mediate the direct contractile action. The response to des-Asp-angiotensin I was qualitatively different from that to angiotensin III i.e. lower potency and a likely higher efficacy suggesting that the two angiotensins act on different subtypes of angiotensin receptor. The response of the aortic rings to angiotensin III and des-Asp-angiotensin I in the SHR was significantly lower than the corresponding responses in WKY. Des-Asp-angiotensin I attenuated in a concentration-dependent and U-shape manner the response of the aortic ring to angiotensin III in the SHR but not in the WKY. Significant attenuation occurred in the pico to nano molar range of des-Asp-angiotensin I which is within the physiological concentration of the nonapeptide. Although these findings are the first demonstration of a direct and modulatory action of des-Asp-angiotensin I on the blood vessels of the SHR and raise the possibility of its involvement in blood pressure control, its exact role remains to be further studied.
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PMID:Actions of des-Asp angiotensin I on the aortic rings of the normo- and hypertensive rats. 950 92

We studied the effects of des-Asp-angiotensin I, a nine amino acid peptide, on cardiac hypertrophy caused by coarctation of the abdominal aorta in Sprague-Dawley rats. The nonapeptide was effective when given either intravenously or orally. Maximum attenuation was observed with an i.v. dose of 153 pmol/day for 4 days, and an oral dose of 250 nmol/day for 4 days. Three mg p.o. losartan, an angiotensin AT1 receptor antagonist, produced comparable attenuation. However, the attenuation produced by des-Asp-angiotensin I but not by losartan was blunted by 30.4 micromol of indomethacin. The oral efficacy of the nonapeptide was partly due to its low effective i.v. doses which were in the nM range. This range is below the Km of most enzymes including those of the intestinal peptidases (the Km of most enzymes is in the microM range). However, the mechanism of absorption of the peptide from the GIT into the systemic circulation remains to be investigated. The findings demonstrate for the first time, the anti-cardiac hypertrophic action of an angiotensin peptide. Unlike the ACE inhibitors and angiotensin receptor antagonists, the nonapeptide acts as an agonist on an indomethacin-sensitive angiotensin receptor to exert its action.
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PMID:Effects of des-Asp-angiotensin I on experimentally-induced cardiac hypertrophy in rats. 957 48

All components of the renin-angiotensin system (RAS) are expressed in the developing kidney in a temporospatial pattern that suggests a role for this system in kidney morphogenesis. Pharmacological blockade of angiotensin actions in fetal and newborn animals results in striking alterations in kidney architecture, including immature glomeruli and papillae, dilated tubuli, and arrested vascular development. Inactivation of angiotensinogen or angiotensin converting enzyme genes in mice results in similar anomalies that begin as subtle alterations in early life and become more pronounced as extrauterine life progresses. However, inactivation of each angiotensin receptor subtype does not result in obvious morphological abnormalities, suggesting functional redundancy at the receptor level. Crossing of mice lacking the various receptor subtypes should be revealing. Overall, the available information suggests that the RAS is necessary for the normal morphological and functional development of the kidney and the preservation of kidney architecture in adult life.
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PMID:Role of angiotensin in renal vascular development. 973 46

These experiments examined the effectiveness of chronic blockade of the renin angiotensin system with either valsartan or benazeprilat on survival, blood pressure and end-organ damage in salt-loaded stroke-prone SHR. Valsartan or benazeprilat given continuously by subcutaneous osmotic minipump beginning at 10.5 weeks of age lowered blood pressure, as determined by radiotelemetry, prevented proteinuria, prolonged survival and decreased the severity of histopathological changes in the heart and kidney. These results indicate that angiotensin receptor blockade affords a similar degree of protection as inhibition of angiotensin converting enzyme in salt-loaded stroke-prone SHR. Furthermore, our results are consistent with a primary contribution of angiotensin II to the maintenance of blood pressure and support a principal role for angiotensin II-dependent mechanisms in the development of end-organ damage in the salt-loaded stroke-prone SHR.
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PMID:Protective effects of valsartan and benazeprilat in salt-loaded stroke-prone spontaneously hypertensive rats. 976 21

Many therapeutic approaches are under evaluation in patients with cardiac failure. They include angiotensin receptor inhibitors, selective and non-selective endothelin receptor inhibitors, neutral endopeptidase inhibitors or mixed inhibitors of neutral endopeptidase and of the angiotensin converting enzyme and, finally, cytokinin modulators. Some of these drugs have already entered Phase II therapeutic trials and are at relatively advanced developmental stages. Others are at preliminary or experimental stages. If these new drugs prove to be effective and well tolerated, they will represent new tools for physicians to treat cardiac failure and prevent its progression. However, many questions concerning drug associations and poly-therapy will be raised, leading to a revision of the strategy of treatment of cardiac failure.
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PMID:[Drugs of the future]. 986 13

Accumulating evidence suggests that angiotensin-(1-7) [Ang-(1-7)] is an important component of the renin-angiotensin system. As the most pleiotropic metabolite of angiotensin I (Ang I) it manifest actions which are most often the opposite of those described for angiotensin II (Ang II). Ang-(1-7) is produced from Ang I bypassing the prerequisite formation of Ang II. The generation of Ang-(1-7) is under the control of at least three enzymes, which include neprilysin, thimet oligopeptidase, and prolyl oligopeptidase depending on the tissue compartment. Both neprilysin and thimet oligopeptidase are also involved in the metabolism of bradykinin and the atrial natriuretic peptide. Moreover, recent studies suggest that in addition to Ang I and bradykinin, Ang-(1-7) is an endogenous substrate for angiotensin converting enzyme. This suggests that there is a complex relationship between the enzymatic pathways forming angiotensin II and other various vasodepressor peptides from either the renin-angiotensin system or other peptide systems. The antihypertensive actions of angiotensin-(1-7) are mediated by an angiotensin receptor that is distinct from the pharmacologically characterized AT1 or AT2 receptor subtypes. Ang-(1-7) mediates it antihypertensive effects by stimulating synthesis and release of vasodilator prostaglandins, and nitric oxide and potentiating the hypotensive effects of bradykinin.
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PMID:Angiotensin-(1-7): a bioactive fragment of the renin-angiotensin system. 987 42

Heart failure is predominantly a disorder of older adults, and to a large extent the epidemiology of heart failure reflects the convergence of age-related changes in the cardiovascular system and the rising prevalence of age-related cardiovascular diseases. The diagnosis of heart failure in the elderly is often difficult because of the presence of atypical symptomatology and comorbid conditions. Similarly, optimal treatment frequently poses a therapeutic challenge because of the high prevalence of confounding medical, behavioral, psychosocial, and economic factors. In addition, there is a paucity of data on the pharmacotherapy of heart failure in the very elderly (over age 80), and in the large proportion of older patients with heart failure and preserved left ventricular systolic function. Despite these difficulties, a number of therapeutic options, including ACE inhibitors, digoxin, and possibly beta blockers and angiotensin receptor antagonists, have been shown to favorably affect the clinical course of heart failure in elderly patients. In addition, several studies have documented the efficacy of multidisciplinary heart failure disease management programs for reducing hospital admission rates, improving quality of life, and decreasing cost of care. At present, the three greatest challenges in managing older heart failure patients are: (1) to more effectively implement proven treatments, such as ACE inhibitors, disease management systems, and antihypertensive therapy; (2) to develop effective therapies for the treatment of diastolic heart failure; and (3) to develop more effective means for heart failure prevention. It is hoped that future studies will address each of these critically important issues.
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PMID:Heart failure. 1009 69

The purpose of this study was to determine whether an angiotensin converting enzyme (ACE) inhibitor, benazepril, and an angiotensin receptor antagonist, valsartan, would decrease atherosclerotic severity in cholesterol-fed rabbits. Male rabbits were fed either: (a) normal rabbit chow; (b) 2% cholesterol diet; (c) 2% cholesterol diet supplemented by benazepril (3 mg/kg per day, subcutaneous injection); or (d) 2% cholesterol diet supplemented by valsartan (1 mg/kg per day, subcutaneous injection). After 12 weeks, the arteries were harvested for histomorphometry and immunohistochemistry. We observed that decreases in serum triglyceride (TG) and total cholesterol (TC) and ACE activity with benazepril-treatment were more than 60, 30, and 84%, respectively, in comparison with the cholesterol group; with valsartan-treatment, TG levels were 53% lower than in the cholesterol group, however, there was no significant difference in TC and ACE activity. The percentage of aortic surface atherosclerotic area, intimal thickness and the ratio of aortic intimal area to medial area were about 40% lower in the benazepril-treated group in comparison with those of the cholesterol group; the difference was more than 60% in the thoracic aorta. The valsartan-treated group had 23% less atherosclerotic area, less effective than benazepril treatment. The percent of PCNA-positive cells and the number of intimal proliferative cells/mm2 were significantly less in the benazepril-treated group compared with the cholesterol group (by 55 and 63%); these parameters were 35 and 17% lower, respectively, with valsartan. The ratio of proliferating macrophages to smooth muscle cells (SMCs) was 3:1 in the cholesterol group, 1:1 in the benazepril and 2:1 in the valsartan-treated group. These results indicate that benazepril could reduce atherosclerotic progression by decreasing macrophage proliferation and accumulation in the arterial wall. The mechanisms for reducing atherosclerotic progression by benazepril and valsartan may be related to reduction of TG and blockade of the angiotensin II action.
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PMID:Antiatherogenic effect of angiotensin converting enzyme inhibitor (benazepril) and angiotensin II receptor antagonist (valsartan) in the cholesterol-fed rabbits. 1021 60

A review of the drug class of angiotensin receptor blockers (ARBs) as well as the ARBs currently available by prescription in the United States is presented. The importance of angiotensin II production by non-angiotensin-converting enzyme (non-ACE) pathways, particularly human chymase, is discussed. Emphasis is placed on the mechanism of action of ARBs and the different binding kinetics of these agents. Although all ARBs, as a group, block the AT1 receptor, they may differ in the pharmacological characteristics of their binding and be classified as either surmountable or insurmountable antagonists. Mechanisms of surmountable and insurmountable antagonism as well as possible benefits of these blocking characteristics are discussed in relation to the various ARBs. The cardiovascular effects of activation of the two main subtypes of angiotensin receptors (AT1 and AT2) are presented. In addition to their treatment of hypertension, ACE inhibitors are recognized as being effective in the management of heart failure, left ventricular hypertrophy, recurrent myocardial infarctions, and renal disease. ARBs are currently indicated only for the treatment of hypertension; however, in vitro and in vivo pharmacological studies as well as preliminary clinical data suggest that ARBs, like ACE inhibitors, may also provide effective protection against end-organ damage in these conditions.
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PMID:Practical considerations of the pharmacology of angiotensin receptor blockers. 1035 58

Pharmacological blockade of the renin-angiotensin system has been found to be a safe and efficacious way to treat hypertension and congestive heart failure. The success of the angiotensin converting enzyme inhibitors has led to interest in alternative ways to block the renin-angiotensin system. Angiotensin II receptor antagonists are a new class of anti-hypertensive drugs that provide a specific blockade of the effects of angiotensin II. Losartan potassium, the first compound of this class, has recently been approved in Japan. It seems likely that the angiotensin receptor antagonists will be suitable to first-line therapy and use of this class for treatment of hypertension will dramatically increase in Japan because of the excellent clinical and laboratory safety profiles.
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PMID:[Angiotensin II receptor antagonists: a review of the development and future perspective]. 1036 27


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