Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies showed that aquaporin 2 (AQP2) is elevated in the kidney of the heart failure rat suggesting that an increased amount of AQP2 contributes to water retention in heart failure. We performed the present study to determine whether angiotensin II play a role in causing an increase in the expression of arginine vasopressin (AVP) V2 and AQP2 mRNA in the kidney of the cardiomyopathic hamster. The expression of AVP V2 and AQP2 mRNA in the inner medullary collecting duct (IMCD) was measured by competitive reverse transcriptase-polymerase chain reaction (RT-PCR) before and after treatment with an angiotensin-converting enzyme inhibitor, enalapril. Our results showed that the expression of AVP V2 (0.53 +/- 0.05 v 1.03 +/- 0.15 amol/microg of total RNA, P <.01) and AQP2 mRNA (0.027 +/- 0.002 v 0.036 +/- 0.002 amol/microg of total RNA, P <.05) in the IMCD of the cardiomyopathic hamster is upregulated. Treating the cardiomyopathic hamster with enalapril for 7 days negated the changes. In situ hybridization experiments confirmed the intensity of the signals for both AVP V2 and AQP2 mRNA was more intense in the IMCD of the cardiomyopathic hamster. Enalapril treatment reduced the signal intensity to a level comparable to the normal hamster. These results suggested that the increases in the expression of AVP V2 and AQP2 mRNA are mediated by angiotensin II.
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PMID:Upregulation of vasopressin V2 and aquaporin 2 in the inner medullary collecting duct of cardiomyopathic hamsters is attenuated by enalapril treatment. 1214 68

At the American College of Cardiology in March two major trials were presented. The publicity surrounding the two could not have been more different. The LIFE demonstrated clear superiority of losartan-based therapy over atenolol-based therapy for the treatment of hypertension. It was published the same week in the Lancet and received major press coverage all over the world. The OVERTURE (Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events) study in contrast received a subdued reception, very little publicity and is yet to be published. 5770 NYHA class II-IV heart failure patients (LVEF<or=30%, recent heart failure hospital admission) were randomised and uptitrated to either 10 mg BD of Enalapril or 40 mg once a day Omapatrilat. The primary end-point of all cause mortality or heart failure related hospitalisation did not differ significantly: 914/2884 for Enalapril and 914/2886 for Omapatrilat (hazard ratio 0.94, CI's 0.86-1.03, P=0.187). Mortality was also similar: 509 for Enalapril and 477 for Omapatrilat (hazard ratio 0.94, CI's 0.83-1.07, P=0.339). Omapatrilat was as good as Enalapril but not better. The worrying trend was however, that angioedema was more common with Omapatrilat; 24 (0.8%) versus 14 cases (0.5%). The OCTAVE (Omapatrilat Cardiovascular Treatment Assessment Versus Enalapril) study was also presented at this time. 25,267 hypertensives were randomised to Omapatrilat or enalapril and a difference of approximately 3 mmHg in favour of Omapatrilat was seen. Significantly more cases of angioedema were seen with Omapatrilat, 274 (2.17%) compared to 86 (0.68%) with enalapril. Overall death rates were similar, 0.18% for enalapril and 0.15% for Omapatrilat. All adverse events were similar, 51.0% for Omapatrilat and 50.4% for enalapril. The rates of angioedema were much higher in blacks, 5.54% for Ompatrilat and 1.62% for enalapril and for smokers, 3.93% for Omapatrilat and 0.81% for enalapril. We were left with a drug that was, for heart failure, not superior to an ACE inhibitor already off patent, and, as an anti-hypertensive, with an angioedema rate more than double that of an ACE inhibitor in a large head to head comparison. The medical community will be watching to make sure these data are published in full in the medical literature in a timely fashion, in the order of end-points specified in the protocol and with appropriate emphasis on the logical points of presentation.
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PMID:Omapatrilat--the story of Overture and Octave. 1295 41

One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of beta-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by 131I-metaiodobenzylguanidine (MIBG), beta-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to beta-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of beta-adrenergic pathway in this model of heart failure.
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PMID:Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and beta-adrenergic desensitization in heart failure after myocardial infarction in rats. 1255 31

Considerable attention has recently focused on the vasopeptidase inhibitors (VPI), a new class of drug that combines angiotensin-converting enzyme (ACE) inhibitor activity with inhibition of natriuretic peptide breakdown. In theory, a drug with these properties may be beneficial both in hypertension and in heart failure. Whilst the efficacy of VPIs in hypertension has been consistently demonstrated in pre-clinical and clinical studies, the role of VPIs, if any, in heart failure is less clear, since numerous small studies have produced conflicting results. Furthermore, preliminary results from the recently completed Omapatrilat Versus Enalapril Randomised Trial of Utility in Reducing Events (OVERTURE) study have failed to establish the VPI, omapatrilat, as a first line therapy in the treatment of chronic heart failure. We review the literature on VPIs in heart failure and discuss possible reasons for the reported lack of benefit over ACE inhibitors.
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PMID:Vasopeptidase inhibitors in heart failure. 1256 65

Although recent trials have shown that antihypertensive treatment can bring about a reduction in stroke, coronary heart disease, heart failure and renal disease, the situation is no longer improving. This is due to the fact that the percentage of hypertensive patients with satisfactory blood pressure is still very poor. International guidelines on hypertension indicate the importance of assessing the absolute risk of patients and the use of a lower dose of drugs to improve the efficacy-tolerability profile. Diuretics used at lower dosage than in the past are effective in reducing morbidity and mortality and continue to be drugs of first choice in the treatment of hypertension. Indapamide sustained release (Natrilix SR) 1.5 mg has an antihypertensive effect equivalent to indapamide immediate release 2.5 mg with a 50% reduction in incidence of serum potassium levels <3.4 mmol/l. Natrilix SR has proved to have a neutral effect both on lipid and glucose profiles and to reduce microalbuminuria in diabetic hypertensive patients. Recent multicentre European clinical trials have shown that Natrilix SR decreases diastolic blood pressure to <90 mmHg in about 75% of patients treated for 1 year. In elderly patients with isolated systolic hypertension, Natrilix SR has been proven to be as effective as amlodipine 5 mg and significantly more effective than hydrochlorothiazide 25 mg. Natrilix SR produces regression of left ventricular hypertrophy which, in the Left ventricular hypertrophy: Indapamide Versus Enalapril study was greater than that induced by enalapril. Natrilix SR represents an appropriate choice not only as a first-line drug in many hypertensive patients but also in at-risk patients like the elderly, subjects with other cardiovascular risk factors, target organ damage, diabetes, or impaired renal function.
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PMID:Clinical role of Natrilix SR in the treatment of at-risk hypertensive patients. 1276 62

Angiotensin-converting enzyme inhibitors have been shown to reduce morbidity and mortality in patients with heart failure. The angiotensin type-1 blocking and cardioprotective properties of perindopril and enalapril were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Enalapril at 20 mg/kg showed the same angiotensin type-1 blocking action as perindopril at 2 mg/kg in rats with heart failure. Twenty-eight days after immunization, surviving Lewis rats (90/120 = 75%) were divided into six groups and administered perindopril at 0.02, 0.2 and 2 mg/kg per day (Groups P0.02, P0.2 and P2), enalapril at 2 and 20 mg/kg per day (Groups E2 and E20) or vehicle alone (Group V, all groups n = 15). After oral administration for 1 month, four of 15 (27%) rats in Group V, and two (13%) in Groups P0.02 and E2 died. None of the animals in Groups P0.2, P2 and E20, or normal rats (Group N) died. Although both angiotensin-converting enzyme inhibitors improved ventricular function in a dose-dependent manner, the left ventricular end-diastolic pressure and area of myocardial fibrosis were lower, and +/- dP/dt was higher in Group P2 (4.9 +/- 0.6 mmHg, 7.5 +/- 1.4% and +2651 +/- 254/-2622 +/- 189 mmHg/s, respectively) than in Group V (16.7 +/- 1.3, 36 +/- 2.6 and +2659 +/- 176/-2516 +/- 205, respectively) and Group E20 (7.5 +/- 2.5, 15.6 +/- 2.0 and +2018 +/- 110/-2097 +/- 102, respectively). Although the expression levels of transforming growth factor-beta1 and collagen-III mRNA in Group V (36.3 +/- 5.7 and 157.6 +/- 12.7%) were significantly higher than those in Group N (19.6 +/- 3.0 and 65.2 +/- 1.5%, both p < 0.01), they were reduced in Group P2 (21.4 +/- 5.9 and 75.2 +/- 9.3%, both p < 0.01). These results suggest that although enalapril can block increases in blood pressure caused by circulating angiotensin type-1, perindopril at 2 mg/kg may confer greater protection than enalapril at 20 mg/kg against injury from the renin-angiotensin system in heart failure.
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PMID:Comparative effects of perindopril with enalapril in rats with dilated cardiomyopathy. 1487 Oct 39

Angiotensin-converting enzyme inhibitors (ACEI) are often used in preventing and treating heart failure due to regurgitant valve disease. The majority of patients with symptomatic rheumatic heart disease (RHD) have significant mitral stenosis (MS) and are denied ACEI therapy, because of the fear of hypotension in the presence of fixed obstruction. The authors assessed the safety and efficacy of ACEI in 109 consecutive patients with RHD and with significant mitral stenosis (mitral valve orifice, MVO < 1.5 cm2)and with NYHA class III or IV heart failure symptoms. Mean age was 33.1+/-12 years, systolic blood pressure (BP) was 111+/-10, and diastolic BP was 73+/-8 mm Hg. MS was significant in 100 patients with mitral regurgitation in 46, aortic regurgitation in 19, and pulmonary hypertension in 60 patients. After initial stabilization, enalapril 2.5 mg bid was started in hospital and titrated up to 10 mg bid over 2 weeks. NYHA status, Borg score, and 6-minute walk test were assessed at baseline, and at 1, 2, and 4 weeks. Seventy-nine of the 100 patients who completed the study had severe MS (MVO < 1.0 cm2). Enalapril was well tolerated by all study patients without hypotension or worsening of symptoms. NYHA class (3.2+/-0.5 baseline vs 2.3+/-0.5 at 4 weeks, p < 0.01) Borg Dyspnea Index (7.6+/-1.3 vs 5.6+/-1.3, p < 0.01), and 6-minute walk distance (226+/-106 vs 299+/-127 m, p < 0.01) improved significantly with enalapril. Patients with associated regurgitant lesions showed more improvement in exercise capacity (120+/-93 vs 39+/-56 m, p < 0.001). Enalapril was well tolerated in patients with RHD with moderate and severe MS. Irrespective of the valve pathology, enalapril improved functional status and exercise capacity with maximum benefit in patients with concomitant regurgitant valvular heart disease.
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PMID:Safety and efficacy of enalapril in multivalvular heart disease with significant mitral stenosis--SCOPE-MS. 1579 4

Calcium channel blockers are used in the treatment of hypertension and angina. The negative findings on cardiovascular outcomes with some short-acting formulations of calcium channel blockers, described in the 1990s, have led to a much reduced use of calcium channel blockers in general. A Coronary disease Trial Investigating Outcome with Nifedipine (ACTION) investigated the effects of the long-acting gastrointestinal therapeutic system (GITS) formulation of nifedipine in patients with stable symptomatic coronary artery disease. There was less new overt heart failure in the nifedipine GITS group (117 of 3825 patients) than in the placebo group (158 of 3840), and coronary angiography and coronary bypass surgery were also lower in the nifedipine GITS than placebo group. Peripheral revascularisation was slightly higher in the nifedipine GITS (187/3825) than the placebo group (144/3840). The Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) trial compared a calcium channel blocker (amlodipine) and angiotensin-converting enzyme inhibitor (enalapril) in normotensive patients with coronary artery disease. The primary outcome of cardiovascular events occurred in 151 (23.1%), 110 (16.6%) and 136 (20.2%) of placebo, amlodipine and enalapril patients, respectively, with the only significant difference being a reduction with amlodipine compared with placebo. This reduction mainly represented a reduction in coronary revascularisation and hospitalisation for angina with amlodipine compared with placebo. These results suggest that calcium channel blockers are safe and beneficial in the treatment of coronary artery disease.
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PMID:Has the controversy over the use of calcium channel blockers in coronary artery disease been resolved? 1593 8

Enalapril (average dose 7,0+/-0.8 mg) was given for 12 weeks to 15 patients with preserved left ventricular (LV) systolic function who had survived large focal myocardial infarction small i, Ukrainian6 months before that. The use of enalapril was associated with 49% lessening of severity of clinical signs of heart failure (p<0.001) and 47% increase of tolerance to physical exercise. It also provided dose dependent 17.8% reduction of LV myocardial mass (p<0.05), normalization of initially "hypertrophic" type of transmitral flow, 21% lowering of LV end diastolic pressure (p<0.05) without effect on LV volume, geometry, global and local systolic function.
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PMID:[Influence of long-term therapy with enalapril on late postinfarction remodeling and functional state of the left ventricle in patients with diastolic heart failure.]. 1648 43

This article reviews reports of ACE inhibitor use in pediatric heart failure and summarizes the present implications for clinical practice. Captopril, enalapril, and cilazapril are orally active ACE inhibitors, and widely used in pediatric cardiology, although more than ten other ACE inhibitors have been applied clinically in adults. Effects of ACE inhibitors on the renin-angiotensin-aldosterone system in pediatric patients are similar to those in adults. ACE inhibitors lower aortic pressure and systemic vascular resistance, do not affect pulmonary vascular resistance significantly, and lower left atrial and right atrial pressures in pediatric patients with heart failure. In infants with a large ventricular septal defect and pulmonary hypertension, ACE inhibitors decrease left-to-right shunt in those infants with elevated systemic vascular resistance. ACE inhibitors induce a small increase in left ventricular ejection fraction, left ventricular fractional shortening, and systemic blood flow in children with left ventricular dysfunction, mitral regurgitation, and aortic regurgitation. These beneficial effects usually persist long term without the development of tolerance. Therapeutic trials of ACE inhibitors have been reported in children with heart failure and divergent hemodynamics, including myocardial dysfunction, left-to-right shunt, such as large ventricular septal defect and pulmonary hypertension, aortic or mitral regurgitation, and Fontan circulation. Hypotension and renal failure usually occur within 5 days after starting ACE inhibition or increasing the dose and, in most cases, recovery is seen after reduction or cessation of the drug. With all ACE inhibitors, smaller doses are administered initially to prevent excessive hypotension, and doses are increased gradually to the target dose. Captopril is administered orally, usually every 8 hours. Daily doses range from 0.3 to 1.5 mg/kg in children. Enalapril is administered orally, once or twice a day, and daily doses range from 0.1 to 0.5 mg/kg. Enalaprilat is administered intravenously, one to three times a day, in doses ranging from 0.01 to 0.05 mg/kg/dose. For the treatment of chronic heart failure in children, ACE inhibitors are essential along with other medications including diuretics, digoxin, and beta-blockers (beta-adrenoceptor antagonists).
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PMID:ACE inhibitors in pediatric patients with heart failure. 1649 12


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