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)

ANP model in rats was used to determine the concentration of TXB2, PGF1 alpha in plasma and the ACE activity in serum in five groups. The concentration of TXB2, PGF1 alpha in all experimental groups was significantly different from that of control group (P < 0.05). The comparison of ACE activity was just the same as the above except that of 6 h. The factors leading to pancreatic ischemia functioned continously. We conclude that pancreatic ischemia is a continuous injury factor in ANP, and there is no reperfusion-injury in the course of the disease.
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PMID:[Pancreatic ischemia: a continuous injury factor in acute necrotic pancreatitis]. 1037 21

The aim of the study was to investigate the influence of long-term ACE inhibition with ramipril on myocardial hypertrophy and its molecular background in spontaneously hypertensive stroke-prone rats (SHR-SP). Therefore, 1-month-old pre-hypertensive SHR-SP were randomized into three groups and exposed lifelong via drinking water to 1 mg/kg/day ramipril (anti-hypertensive dose, RHI), 10 micrograms/kg/day ramipril (non-anti-hypertensive dose, RLO) or placebo. After 15 months cardiac tissue was collected from ten rats each for immunohistochemistry and Northern blot analysis of structural proteins, proteins of the extracellular matrix and several growth factors. Results showed that RHI, but not RLO, treatment prevented development of myocyte hypertrophy (ANP). Furthermore, unlike placebo-treated rats, the ramipril-treated animals had no evidence of degeneration and loss of structural proteins (alpha -actinin), inflammatory infiltrates (CD45) and deposition of extracellular matrix proteins (collagen, fibronectin, vimentin). Only in RHI-treated animals, mRNA levels for TGF- beta(1)as well as of collagen alpha(1)(I) and fibronectin were downregulated compared to placebo-treated animals. In contrast, VEGF mRNA levels increased significantly in both groups of ramipril-treated animals v. placebo-treated SHR-SP. Thus, the reported life prolonging effect of high doses of ramipril which is associated with prevention of hypertension and hypertrophy is accompanied by prevention of the development of necrosis and fibrosis. The role of VEGF, however, seems to be independent of this effect.
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PMID:Effect of long-term ACE inhibition on myocardial tissue in hypertensive stroke-prone rats. 1042 43

Essential Hypertension (EH) is a multifactorial and polygenic syndrome with a high impact in public health. Recently, rare mendelian forms of hypertension such as glucocorticoid-remediable aldosteronism (GRA), apparent mineralocorticoid excess (AME) and Liddle Syndrome caused by single gene mutations have been identified in which the mechanism is an increased sodium retention. Therefore, it is tempting to speculate that the most common forms of EH may be due to diverse highly prevalent molecular variants of susceptibility genes with low penetrance that are involved in arterial blood pressure (ABP) and electrolytic balance. Although a number of candidate genes such as NO synthases, ANP, ion transporters, adducins, LDL receptor, etc. can participate, renin-angiotensin system components are the most extensively studied. Although not associated with EH, the ACE D allele seems to confer a high risk of CHD or LVH. Angiotensinogen 235T and 174M variants are more likely associated with EH and positively correlate with clinical or ambulatory ABP in adolescents or adults. Individuals who carry these angiotensinogen alleles would be at 1.4 higher risk of suffering EH than homozygotes for M235 or T174 alleles. Associations of AT1 receptor variants with EH remain to be definitively defined. In conclusion, the characterization of the genetic background, although difficult at the present time, may have clear benefits in terms of defining a more rational therapy and prevention in individuals at risk. Even though this aim seems difficult to achieve since more than 150 candidate genes have been postulated as the cause of EH, with 6 to 10 SNPs in each of them, new technologies such as DNA micro-arrays will provide us with the opportunity to analyse the total genetic risk in each subject.
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PMID:[Molecular genetics of essential hypertension. Susceptibility and resistance genes]. 1083 1

The important neuroendocrine systems implicated in heart failure are reviewed here, with special emphasis on their possible role in pathophysiology and the chances of pharmacological intervention. The part played by the sympathetic nervous system and the renin-angiotensin-aldosterone system and the beneficial effects of beta-blockers, ACE inhibitors, and angiotensin II antagonists are well-established. The involvement of vasopressin, endothelin-1, ANP, BNP, and TNF-alpha and the interventional possibilities relating to these hormones are also discussed. It is concluded that, in addition to the known interventional principles of neuroendocrine activation, there is a series of new exciting principles and some of them might become important in the future.
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PMID:[Neuroendocrine activation in heart failure I. Pathophysiology and pharmacological intervention]. 1109 49

The aim of the present study was to evaluate the possible interaction between chronic aspirin therapy and angiotensin-converting enzyme inhibitor (ACE-I) on left ventricular ejection fraction (LVEF) in patients surviving an acute myocardial infarction (AMI). Forty-two patients with reduced LVEF were recruited from the warfarin aspirin reinfarction study (WARIS-II), a randomized, open study comparing enteric coated aspirin (160 mg/d), warfarin (INR 2.8--4.2) and the combination of aspirin (75 mg/d) and warfarin (INR 2.0--2.5) on mortality, reinfarction and stroke after AMI. LVEF and relevant biochemical measurements were performed before discharge and after 3 months. The overall LVEF increased during the study period from median 35 to 39% (P<0.001). There was no difference between patients on aspirin and warfarin regarding the main end point, LVEF. Furthermore, neither endothelin-1 nor ANP showed significant differences between the treatment groups. A possible interaction between ACE-I and aspirin might theoretically lead to reduced levels of renin activity in patients on aspirin, but we did not find any such inter-group difference. In conclusion, we did not find evidence of interaction between ACE-I and low-dose aspirin.
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PMID:Aspirin does not influence the effect of angiotensin-converting enzyme inhibition on left ventricular ejection fraction 3 months after acute myocardial infarction. 1124 58

There is now substantial evidence supporting a role of the natriuretic peptides as a major defence mechanism against excess salt and water retention and high blood pressure. Because of this there has been considerable interest in the therapeutic potential of the natriuretic peptide system. Several approaches have been explored including the use of native peptides, the development of natriuretic peptides mimetics and targetting of endogenous clearance of natriuretic peptides. While ANP and BNP administration may be valuable in some circumstances, however, the limitations of the use of peptides especially for long-term treatment are well apparent. In view of this, considerable effort has been devoted to the development of orally active agents to enhance endogenous natriuretic peptides through inhibition of breakdown by neutral endopeptidase. This research has now led to the vasopeptidase inhibitors - dual inhibitors of both endopeptidase and angiotensin converting enzyme. These agents clearly provide a novel approach to enhance endogenous natriuretic peptide function on a background of reduced angiotensin II activity and may lead to an important advance in the treatment of hypertension and of conditions associated with overt salt and water overload.
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PMID:Atrial natriuretic peptide mimetics and vasopeptidase inhibitors. 1147 32

In addition to cardiac myocyte hypertrophy, proliferation and increased extracellular matrix production of cardiac fibroblasts occur in response to cardiac overload. This remodeling of the cardiac interstitium is a major determinant of pathologic hypertrophy leading to ventricular dysfunction and heart failure. Atrial and brain natriuretic peptides (ANP and BNP) are cardiac hormones produced primarily by the atrium and ventricle, respectively. Plasma ANP and BNP concentrations are elevated in patients with hypertension, cardiac hypertrophy, and acute myocardial infarction, suggesting their pathophysiologic roles in these disorders. ANP and BNP exhibit diuretic, natriuretic, and vasodilatory activities via a guanylyl cyclase-coupled natriuretic peptide receptor subtype (guanylyl cyclase-A or GC-A). Here we report the generation of mice with targeted disruption of BNP (BNP-/- mice). We observed focal fibrotic lesions in ventricles from BNP-/- mice with a remarkable increase in ventricular mRNA expression of ANP, angiotensin converting enzyme (ACE), transforming growth factor (TGF)-beta3, and pro-alpha1(I) collagen [Col alpha1(I)], which are implicated in the generation and progression of ventricular fibrosis. Electron microscopic examination revealed supercontraction of sarcomeres and disorganized myofibrils in some ventricular myocytes from BNP-/- mice. No signs of cardiac hypertrophy and systemic hypertension were noted in BNP-/- mice. In response to acute cardiac pressure overload induced by aortic constriction, massive fibrotic lesions were found in all the BNP-/- mice examined, accompanied by further increase of mRNA expression of TGF-beta3 and Col alpha1(I). We postulate that BNP acts as a cardiocyte-derived antifibrotic factor in the ventricle.
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PMID:Brain natriuretic peptide appears to act locally as an antifibrotic factor in the heart. 1155 81

A study was designed to elucidate the mechanism of anti-hypertensive effects of danshen in the two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive model, which is the renin-angiotensin system (RAS)-dependent hypertensive model. We investigated the effects of water extracts of danshen on the angiotensin converting enzyme (ACE) activities, systolic blood pressure (SBP), and hormone levels in the plasma of 2K1C rats. ACE activity was inhibited by the addition of danshen extract in a dose-dependent manner. SBP was decreased significantly after administration of danshen extract in 2K1C, whereas plasma renin activity (PRA) was not changed. The plasma concentration of aldosterone (PAC) was decreased significantly in 2K1C group administered with Danshen extract, whereas the plasma concentration of ANP was increased by administration of danshen extract for three weeks. These results suggest that danshen has an anti-hypertensive effect through the inhibition of ACE, an essential regulatory enzyme of RAS.
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PMID:Anti-hypertensive effect of water extract of danshen on renovascular hypertension through inhibition of the renin angiotensin system. 1206 1

The effect of long-term administration of delapril, an angiotensin converting enzyme inhibitor, and candesartan, an angiotensin II receptor blocker, on cardiac hypertrophy was investigated in spontaneously hypertensive rats (SHR). Delapril (2 mg/kg/ day) and candesartan (2 mg/kg/day) were administered for 5 weeks to 15-week-old male SHR. Echocardiographic estimation of cardiac morphology and function revealed cardiac hypertrophy in SHR compared with Wistar-Kyoto rats (WKY) which were used as normal controls. Both treated groups revealed regression of cardiac hypertrophy estimated by echocardiography. Heart to body weight ratio of treated SHR was also smaller than that of untreated SHR. Plasma BNP and ANP concentrations were increased in untreated SHR and decreased in the treated groups. Histological examination was performed using light microscopy and the area of fibrosis was estimated by computer. Reduction of the fibrotic area was observed in SHR treated with delapril and candesartan, although the latter was not statistically significant. Immunohistochemical examination using anti-collagen monoclonal antibody showed a decrease of type I collagen in treated SHR as compared with untreated SHR. It is concluded that both angiotensin converting enzyme inhibitor and angiotensin II receptor blocker sufficiently reduce blood pressure in SHR associated with regression of cardiac remodeling.
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PMID:Effect of an ACE inhibitor and an AT1 receptor antagonist on cardiac hypertrophy. 1287 Jun 74

Chronic heart failure is a slowly progressive disease. Hemodynamic deterioration activates various neuro-humoral factors and increases stresses, such as catecholamine, angiotensin II (AII), cytokines, endothelin, wall stress, ischemia, tachycardia, and oxidative stress. These factors affect the myocardium to cause phenotype switching, leading to ventricular remodeling. We investigated the effects of pharmacological blocking for neuro-humoral factors in rats with dilated cardiomyopathy. Experimental autoimmune myocarditis (EAM) was elicited in Lewis rats by immunization with cardiac myosin. After acute inflammation healed, rats were treated with angiotensin converting enzyme inhibitors (ACEI), type 1 AII receptor blockers, and amiodarone. These agents had favorable effects on hemodynamics and myocardial contractility, prevented fibrosis, suppressed the expression of ANP, and reversed phenotypic change of cardiac myosin. AII receptor blockers were less effective than ACEI. In order to prevent ventricular remodeling in chronic heart failure, wide and complete blocking of neuro-humoral factors is important.
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PMID:[Effects of humoral factors on left ventricular remodeling under chronic heart failure]. 1474 25


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