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)

Experimental and clinical evidence suggest that angiotensin converting enzyme (ACE) inhibition may reduce cardiovascular (CV) risk by directly affecting endothelial dysfunction, atherosclerosis and thrombus formation. These direct effects are in addition to effects on vascular tone or pressure. The Health Outcomes and Prevention Evaluation (HOPE) study assessed the role of an ACE inhibitor ramipril in reducing CV events in 9297 patients > or = 55 years who were at high risk of CV events but did not have left ventricular dysfunction, heart failure, or high blood pressure at the time of study entry. In the overall HOPE population, the risk of the primary composite outcome (cardiovascular death, myocardial infarction, or stroke) was reduced by 22% (p < 0.001), and in patients with diabetes plus one other CV risk, it was reduced by 25% (p = 0.0004). Ramipril treatment achieved risk reduction in patients with mild renal insufficiency (serum creatinine > or = 1.4 mg/dl). Ramipril treatment did not increase adverse events in patients with renal insufficiency. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and Vitamin E (SECURE) demonstrated that ramipril 10 mg significantly reduced the rate of carotid intimal medial thickening, suggesting a direct effect on atherosclerotic progression.
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PMID:What should the role of ACE inhibitors be in the treatment of diabetes? Lessons from HOPE and MICRO-HOPE. 1184 51

Given the significant public health impact of stroke and the identification of nonmodifiable (age, gender, race/ethnicity) and modifiable (blood pressure, diabetes, lipid profile, and lifestyle) risk factors, early prevention strategies should be initiated. When a patient suffers a stroke, the focus of care becomes prevention of future events. For the patient with diabetes, comprehensive medical management of ischaemic stroke (primary or secondary prevention) includes antihypertensive and lipid-lowering therapy, as well as antiplatelet therapy. Despite the cerebrovascular risk reduction with these modalities, clearly new agents are needed. The Heart Outcomes Prevention Evaluation (HOPE) study provides compelling evidence that treatment with the angiotensin converting enzyme inhibitor, ramipril, can further reduce the risk of stroke in high-risk patients by mechanisms other than lowering blood pressure. In HOPE, patients were normotensive at baseline. Therefore, for the first time, in a patient population without left ventricular dysfunction, the effects of an ACE inhibitor ramipril on reducing stroke risk were demonstrated. Ramipril 10 mg achieved a significant 33% reduction in stroke among patients with diabetes. Based on the HOPE study, the recently published American Heart Association guidelines for the primary prevention of stroke recommend ramipril to prevent stroke in high-risk patients and in patients with diabetes and hypertension. Wide-scale adherence to these guideline recommendations for the prevention of primary and secondary stroke would significantly benefit the public health.
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PMID:Reducing the risk of stroke in diabetes: what have we learned that is new? 1184 52

Foam cell formation, the hallmark of early atherosclerosis, results from cholesterol accumulation in arterial macrophages. Angiotensin-II stimulates foam cell formation and angiotensin converting enzyme (ACE) inhibitors reduce atherosclerosis in animal models. The goal of the present study was to determine the effect of the ACE inhibitor Ramipril on the progression of atherosclerosis in apolipoprotein-E-deficient (E0) mice with already advanced atherosclerosis. Therefore, 4-month-old atherosclerotic E0 mice were treated with Ramipril for 2 and 4 months and compared to age-matched placebo-treated mice, as well as to control young (4-month-old) non-treated E0 mice, for their atherosclerosis. Histomorphometry showed that Ramipril treatment substantially inhibited atherogenesis as shown by 48 and 72% reduction in lesion size at 6 and 8 months of age, respectively, compared to the lesion size in age-matched placebo-treated mice. Moreover, the size of the atherosclerotic lesions in 6- and 8-month-old Ramipril-treated mice was almost identical to the size of atherosclerosis of the 4-month-old control mice. Moreover, Ramipril treatment of E0 mice, significantly reduced oxidized low-density lipoprotein (Ox-LDL) uptake by their peritoneal macrophages (MPM) by 32%, compared to Ox-LDL uptake by MPM from 6-month-old placebo mice, and even reduced it by 12% in comparison to Ox-LDL uptake by MPM from 4-month-old control mice. A significant decrease in the mRNA levels of the Ox-LDL receptor CD36 by 58% was observed in macrophages from 6-month-old Ramipril-treated mice compared to macrophages from the 6-month-old placebo-treated mice. There was even a significant reduction (by 32%) in CD36 mRNA levels in macrophages from the 6-month-old Ramipril-treated mice, compared to the CD36 mRNA levels in macrophages from the 4-month-old control mice. We thus conclude that administration of the ACE inhibitor Ramipril to E0 mice, which already exhibit significant atherosclerosis, blocked the progression of the atherosclerotic lesion build-up, a phenomenon that could be related to Ramipril-induced inhibition of Ox-LDL uptake by macrophages.
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PMID:Ramipril administration to atherosclerotic mice reduces oxidized low-density lipoprotein uptake by their macrophages and blocks the progression of atherosclerosis. 1188 18

To explore the effect of angiotensin converting enzyme (ACE) inhibitor on apoptosis in spontaneously hypertensive rats(SHR), and normotensive control rats (WKY) at different ages were used. Ramipril (1 mg.kg-1.d-1) was administered orally to male SHR from 3 or 5 weeks to 10 weeks of age. Male and age-matched untreated SHR and WKY were used as controls. Experiments determined. Apoptosis in cardiomyocytes of SHR was quantified by a maximal labeling (Lmax) method and the characteristic features of apoptosis were identified by electron microscopy (EM), in situ labeling of DNA strand breaks with terminal deoxynucleotidyl transferase mediated dUTP end labeling (TUNEL) and autoradiographic analysis of DNA fragments. The results of the quantitative method showed an age-dependent increase in apoptosis in the cardiac tissues of SHR. A significant increase in DNA breaks occurred as early as age 4 weeks and continued to increase up to a plateau at age 16 weeks in the cardiac tissue of SHR, whereas there was no significant change in apoptosis in WKY up to 64 weeks. Moreover, after the treatment of SHR with ramipril, an inhibitor of ACE, the DNA fragmentation, like BP and HW/BW, was reduced significantly (70.7%) as compared with that of untreated SHR(P < 0.01); and similar to that of the WKY (P > 0.1), the DNA ladder disappeared, which was very obvious in the untreated SHR. These studies demonstrate that ramipril can prevent the development of hypertension and myocardial hypertrophy and can inhibit the increase in the apoptosis of SHR cardiac myocytes, suggesting that apoptosis may be involved in the pathogenesis of genetic hypertension.
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PMID:[Investigation of inhibitory effect of ramipril on apoptosis in spontaneously hypertensive rats]. 1220 19

Numerous studies have emphasized the important role of altered Ca(2+) channel function in hypertension. We previously showed that Ca(2+) currents measured in myocytes isolated from both Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) small mesenteric arteries closely correlated with systolic blood pressure (BP) during normal development. The purpose of the present experiments was to determine whether antihypertensive therapy with an angiotensin converting enzyme inhibitor normalizes Ca(2+) channel function in SHR myocytes along with BP. Ramipril (3.5 mg/kg/day) was added to the drinking water of 12-week-old male WKY and SHR for 8 weeks. Segments of small mesenteric arteries were used for isometric contraction studies, and for isolation of myocytes for measurement of Ca(2+) and K(+) currents (I(Ca) and I(K)) by patch clamp methods. Ramipril treatment decreased systolic pressure in WKY and SHR, decreased heart weight and heart weight-to-body weight ratio in SHR, and decreased body weight in WKY. Maximum contractile responses to Bay k 8644 in SMA from ramipril-treated SHR were smaller compared to untreated SHR (10% +/- 2% v 55% +/- 7% of the response to 120 mmol/L KCl). The smaller responses in WKY were not affected by ramipril treatment (11% +/- 4% v 8% +/- 3%). Contractile responses to 10 mmol/L tetraethylammonium (TEA) were not different in untreated versus ramipril-treated SHR (65% +/- 6% v 82% +/- 8%) but were increased in treated WKY (4% +/- 1% v 35% +/- 9%). Ramipril treatment decreased peak I(Ca) and equalized the voltage-dependence of I(Ca) activation between SHR and WKY. The I(K) measured from holding potentials of -60 and -20 mV were significantly smaller in treated SHR and WKY compared to their untreated counterparts, as was the component of I(K) measured in the presence of 100 nmol/L iberiotoxin. These results show that ramipril treatment decreases arterial pressure and Ca(2+) channel function in SHR as expected but unexpectedly also decreases I(K) in both WKY and SHR. These results suggest that angiotensin may have a BP independent effect on ion channel function in arterial smooth muscle.
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PMID:Ramipril treatment alters Ca(2+) and K(+) channels in small mesenteric arteries from Wistar-Kyoto and spontaneously hypertensive rats. 1237 75

ACE inhibition reduces plasminogen activator inhibitor-1 (PAI-1), a risk factor for myocardial infarction, whereas the effect of angiotensin receptor antagonism on PAI-1 is uncertain. The present study compares the time course of effects of ACE inhibition and angiotensin type 1 (AT1) receptor antagonism on morning plasma PAI-1 antigen. Blood pressure and endocrine, metabolic, and fibrinolytic variables were measured in 20 insulin-resistant (defined by fasting glucose >8.3 mmol/L, body mass index >28 kg/m2, or fasting serum triglyceride > or =2.8 mmol/L) hypertensive subjects (mean age, 47.9+/-2.1 years) (1) before and after 1 week of hydrochlorothiazide 12.5 mg/d, and (2) before and 1, 3, 4, and 6 weeks after addition of ramipril (escalated to 10 mg/d) or losartan (escalated to 100 mg/d). Hydrochlorothiazide decreased systolic (P=0.011) and diastolic (P=0.019) pressure. Ramipril (from 133.6+/-5.1/94.5+/-2.4 to 127.0+/-3.1/91.4+/-3.3 mm Hg) or losartan (from 137.0+/-3.9/93.1+/-2.9 to 123.7+/-2.6/86.4+/-2.1 mm Hg) further reduced systolic (P=0.009) and diastolic (P=0.037) pressure. The pressure effects of the 2 drugs were similar. Hydrochlorothiazide increased plasma PAI-1 (P=0.013) but not tissue-type plasminogen activator (tPA) (P=0.431) antigen. Addition of either ramipril or losartan significantly decreased plasma PAI-1 antigen (P=0.046). However, the effect of losartan on PAI-1 antigen was not sustained throughout the 6-week treatment period, such that there was a significant drugxtime interaction (P=0.043). tPA antigen decreased during either ramipril or losartan (P=0.032), but tPA activity decreased only during losartan (P=0.018). Short-term interruption of the renin-angiotensin-aldosterone system by either ACE inhibition or AT1 receptor antagonism decreases PAI-1 antigen, but the duration of this effect is greater for ACE inhibition than for AT1 receptor antagonism.
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PMID:ACE inhibition versus angiotensin type 1 receptor antagonism: differential effects on PAI-1 over time. 1246 70

The circulation in the left and right coronary beds in pressure overload-induced left ventricular (LV) hypertrophy was studied in Wistar male rats (n=6/group) that were subjected to abdominal aortic constriction or to sham-operation. From 3 to 6 weeks after surgery, the animals with aortic constriction received vehicle or 0.01, 0.1, or 1 mg/kg per day po of the angiotensin converting enzyme (ACE) inhibitor, ramipril. At 6 weeks, after measuring blood pressure in the carotid artery in vivo, the hearts were isolated and the left and right coronary beds subjected to independent perfusion. Minimum coronary vascular resistance per unit heart weight (MCVR/g) was determined in both beds during simultaneous infusion of 10 micromol/L adenosine. Aortic constriction resulted in a significant increase in blood pressure, LV weight/body weight ratio, and bilateral MCVR/g. Ramipril lowered arterial pressure in a dose-dependent manner and reversed the increased right MCVR/g at the anti-hypertensive dose, but it did not affect LV mass or left MCVR/g. These results suggest that both coronary hypertension and myocardial hypertrophy contribute to the global impairment of coronary circulation in LV hypertrophy. ACE inhibitors may improve coronary circulation in LV hypertrophy when administrated at an appropriate dose and for a sufficient period.
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PMID:Left and right coronary circulation in left ventricular hypertrophy: effects of angiotensin converting enzyme inhibition. 1249 26

The aim of this work was to ascertain, in nonmodulating essential hypertension, whether the abnormality in the renal blood supply is extended to the extremities and showed a similar response to ACE inhibition and whether these abnormalities could be identified in normotensive offspring of hypertensives, as non-modulation is a familial process with genetic underpinnings. We measured forearm vascular blood flow (FBF) and forearm vascular resistance (FVR) by plethysmography and urinary albumin excretion in 20 normotensive without family story of hypertension (NT: 25+/-9 years), 10 modulating offspring of hypertensive parents (MHO: 25+/-6 years), 10 nonmodulating offspring of hypertensive parents (NMHO: 26+/-5 years), 12 modulating essential hypertensives (MHT: 34+/-5 years), and 11 nonmodulating essential hypertensives (NMHT: 32+/-4 years). Measurements were repeated in hypertensives after 3-month treatment with ramipril (5 mg daily). Nonmodulating individuals showed lower maximum FBF (NMHT: 41.96+/-3.3 mL/100 g per minute and NMHO: 35.6+/-9.0 mL/100 g per minute) than modulating subjects (MHT: 57.5+/-10.0 mL/100 g per minute and MHO: 51.8+/-7.0 mL/100 g per minute; P<0.003). Likewise, all nonmodulating subjects showed higher minimum FVR (NMHT: 2.5+/-0.2 AU; NMO: 2.8+/-0.5 AU) than modulating individuals (MHT: 1.9+/-0.5 AU; MHO, 1.8+/-0.3AU; P<0.025). Urinary albumin excretion was higher in NMHT and NMHO than MHT, MHO, and NT (P<0.05). Ramipril increased maximum FBF to 53.8+/-8.0 mL/100 g per minute and reduced minimum FVR to 1.9+/-0.5 AU in NMHT (P<0.01). Likewise, ramipril increased effective renal plasma flow and reduced renal vascular resistance and urinary albumin excretion only in NMHT (P<0.05). These results have shown an early involvement of the peripheral circulation in association with increased urinary albumin excretion not only in essential hypertensives but also in NMHO. The effectiveness of ramipril in reducing minimum FVR and urinary albumin excretion in NMHT also suggests a common mechanism.
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PMID:Parallel renal and extremity blood supply abnormalities in nonmodulation: responses to ACE inhibition. 1264 7

Enhanced oxidative stress is involved in the progression of renal disease. Since angiotensin converting enzyme inhibitors (ACEI) have been shown to improve the antioxidative defence, we investigated, in patients with nondiabetic nephropathy, the short-term effect of the ACEI ramipril on parameters of oxidative stress, such as advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), homocysteine (Hcy), and lipid peroxidation products. Ramipril (2.5-5.0 mg/day) was administered to 12 newly diagnosed patients for 2 months and data compared with a patient group under conventional therapy (diuretic/beta-blockers) and with age- and sex-matched healthy subjects (CTRL). Patients had mild to moderate renal insufficiency and showed, in the plasma, higher fluorescent AGE and carboxymethyllysine (CML) levels, as well as elevated concentrations of AOPPs, lipofuscin and Hcy when compared with CTRL. Basal data of the patients on conventional therapy did not differ significantly from the ramipril group, except for higher Hcy levels in the latter. Administration of ramipril resulted in a drop in blood pressure and proteinuria, while creatinine clearance remained the same. The fluorescent AGEs exhibited a mild but significant decline, yet CML concentration was unchanged. The AOPP and malondialdehyde concentrations decreased, while a small rise in neopterin levels was evident after treatment. The mentioned parameters were not affected significantly in the conventionally treated patients. Evidence that ramipril administration results in a mild decline of fluorescent AGEs is herein presented for the first time. The underlying mechanism may be decreased oxidative stress, as indicated by a decline in AOPPs and malondialdehyde.
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PMID:Effects of ramipril in nondiabetic nephropathy: improved parameters of oxidatives stress and potential modulation of advanced glycation end products. 1269 71

This longitudinal prospective study was designed to assess the effects of the angiotensin converting enzyme inhibitor (ACEI) ramipril on ventricular mass, left ventricle (LV) diastolic function and blood pressure in patients with mild to moderate essential hypertension and hyperinsulinemia. LV diastolic dysfunction is the first target organ alteration occurring in hypertensive patients, while ventricular hypertrophy is the most relevant predictive factor for cardiovascular morbility and mortality in systemic hypertension. Because several studies have demonstrated that there is no direct correlation between blood pressure values and the severity of LV hypertrophy or diastolic dysfunction, it is assumed that other factors are involved in the genesis of these functional alterations. Moreover, the hypertensive effect of insulin is caused by sympathetic stimulation, sodium and water renal retention and protooncogene stimulation leading to myocardial and vascular fibrosis and hypertrophy. We studied 24 hypertensive patients with hyperinsulinemia. All patients underwent an overall and cardiologic clinical evaluation, and electrocardiographic and ecocardiographic studies were performed at baseline and 6 months after being treated with 2.5 to 5 mg/day ramipril. Ramipril treatment significantly reduced systolic (12 mmHg) and diastolic (12 mmHg) pressure levels, basal insulin serum levels (23.62 pmol/dL vs 10.42 pmol/dL), and left ventricle mass index values (143.8 g/m2 vs 118.2 g/m2). Among the variables assessing LV diastolic function, only the transmitral flow E/A wave ratio showed significant differences in women. Ramipril was well tolerated and no significant adverse events were reported.
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PMID:[Effect of ramipril on the glucose/insulin coefficient and the ventricular mass index in patients with light to moderate arterial hypertension]. 1282 Apr 91


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