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)

The endothelium controls vascular smooth muscle tone by secreting relaxing and contracting factors. There is a constant release of endothelium-derived relaxing factors(s) (EDRF) under basal conditions. In addition, the endothelium can increase the release of EDRF in response to humoral stimulation by vasoactive substances such as acetylcholine or bradykinin. Under physiological conditions the most important stimulus to the release of EDRF is an increase in blood flow, leading to increased shear stress on endothelial cells. Recent experimental studies have raised the possibility that bradykinin plays an important role in the regulation of vascular tone at rest and during flow-stimulated conditions. Bradykinin is a very potent vasodilator that exerts its vasodilatory actions by causing endothelial release of nitric oxide, prostacyclin and/or endothelium-derived hyperpolarizing factor. Recent studies in humans have demonstrated that bradykinin contributes to the regulation of coronary vascular tone under resting and flow-stimulated conditions. This mechanism has been shown to be important in humans in both peripheral and coronary arteries. Angiotensin-converting enzyme (ACE) inhibitors not only decrease angiotensin II but also increase bradykinin levels, since ACE is identical to kininase II, which degrades bradykinin. The beneficial vascular effects of ACE inhibitors may therefore be related to increased availability of bradykinin. Indeed, we have recently shown that ACE inhibition improves flow-dependent, endothelium-mediated vasodilation and that this beneficial effect is bradykinin-dependent. Our preliminary data also indicate that ACE inhibition improves endothelium-mediated vasodilation in patients with heart failure and coronary artery disease due to an enhanced availability of nitric oxide. These findings suggest that the beneficial vascular effects of ACE inhibition in heart failure may be due in part to improved endothelial function.
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PMID:Effect of ACE inhibition on endothelial dysfunction in patients with chronic heart failure. 971 56

Angiotensin-converting enzyme (ACE) inhibitors have been shown in several large studies to prolong life and prevent disease progression in patients with heart failure and to prevent progression of left ventricular dysfunction following myocardial infarction. Despite this, it appears that a significant proportion of eligible patients are not receiving these agents and not obtaining their benefits. Patients in clinical trials are generally more selected and homogeneous than heart failure patients in the community. Clinicians may often feel that the typical clinical trial patient is not representative of many patients in their own practices and that trial results are often not generalizable to practice. It is only with the emergence of evidence from trials which more closely represent community practice and the promotion of agreed management guidelines that ACE inhibitors will be used more widely. Specialists and primary care practitioners need to provide an integrated approach to heart failure management to achieve optimal outcomes for patients.
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PMID:Translation of clinical trial results into practice. 982 Oct 6

Conductance of alveolar capillary membrane (DM) and capillary blood volume (VC) are the subcomponents of the pulmonary diffusing capacity for carbon monoxide (DLCO). In chronic heart failure, stress failure of the membrane provides a mechanism for reduced DM and subsequent impairment of DLCO. Angiotensin-converting enzyme inhibition improves DLCO in patients with chronic heart failure. This study was aimed at investigating which of the two subcomponents of DLCO is affected by angiotensin-converting enzyme inhibitors. Twenty-seven patients with NYHA class II to III chronic heart failure (group 1) and 13 age- and sex-matched normal subjects underwent pulmonary function testing with determination of DM and VC, while receiving placebo and 48 h and 1 and 2 months after starting enalapril treatment (10 mg twice daily). Nine similar patients (group 2) received isosorbide dinitrate (40 mg thrice daily) for a month then enalapril for another month, and underwent pulmonary function testing at 48 h and 1 month after starting treatments. Effects of angiotensin-converting enzyme inhibition in normal controls were not significant in the short- or mid-term. In group 1 patients, the only change observed at 48 h was a reduction in VC (probably due to a decrease in capillary pulmonary pressure). There was a marked increase in DM to a similar extent at 1 and 2 months, resulting in a significant improvement in DLCO despite a decrease in VC. In group 2 patients, nitrates failed to improve DLCO and DM, whereas enalapril was as effective as in group 1. These observations suggest a modulatory effect of angiotensin-converting enzyme inhibition on the membrane function which emerges gradually and persists over time and is probably dissociated from changes in pulmonary capillary pressure and VC. Chronic heart failure disturbs the alveolar capillary interface and increases gas diffusion resistance; angiotensin-converting enzyme inhibition restores the diffusive properties of the membrane and gas transfer, and protects the lung when the heart is failing.
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PMID:Angiotensin-converting enzyme inhibition restores the diffusing capacity for carbon monoxide in patients with chronic heart failure by improving the molecular diffusion across the alveolar capillary membrane. 985 2

Haemostasis depends on an intricate relation among plasma coagulation and fibrinolytic factors, blood cells, vessel walls, extracellular matrix, blood viscosity, and blood flow. Hormonal systems, such as the renin-angiotensin system (RAS) act as a protector against acute fluid volume loss by inducing both vasoconstriction to maintain blood pressure and the retention of salt and water to restore normal fluid volume. Studies have confirmed that this cascade of events is brought into action by the RAS in coordination and sequentially. Inappropriate activation of the RAS may occur, however, in patients with left ventricular dysfunction and heart failure. Angiotensin-converting enzyme inhibitors are indicated to counteract the vasoconstriction and salt and water retention associated with activation of the RAS.
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PMID:The renin-angiotensin system and vascular fibrinolytic balance. 992 41

Angiotensin-converting enzyme (ACE) inhibitors have been in clinical use for 20 years, during which time their application has been extended from the treatment of hypertension and heart failure to left ventricular dysfunction after myocardial infarction. They are also being used today for the treatment of diabetic nephropathy. More recently, the rationale for an antiatherosclerotic effect of ACE inhibition has emerged, based on more detailed understanding of the renin-angiotensin-aldosterone system and the role of this system in atherogenesis, in addition to supportive experimental animal and preliminary clinical data. The possible clinical benefit of ACE inhibition in atherosclerosis is currently being assessed in several large-scale trials with both surrogate and clinical outcome measures in high-risk patients with clinically manifest atherosclerosis, principally coronary artery disease. The trials should further elucidate the mechanisms of benefit from ACE inhibition and further define their role in therapy of patients with coronary disease.
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PMID:Towards 2001: will ACE inhibitors have a role in atherosclerosis treatment? 992 42

Angiotensin-converting enzyme (ACE) inhibitors have proven an effective means to control hypertension and manage cardiac hypertrophy. It is presently unknown if newer specific angiotensin II subtype 1 receptor (AT1R) antagonists are as effective or more effective in treating these conditions compared with ACE inhibitors. There is evidence that these classes of drugs may affect cardiac hypertrophy by different mechanisms. This study compared the effect of irbesartan, an AT1R antagonist, with that of captopril, an ACE inhibitor, on expression of early genetic markers of cardiac hypertrophy in lean male SHHF/Mcc-fa(cp) rats. SHHF/Mcc-fa(cp) rats (n = 10/group) were given captopril (100 mg/kg/day), irbesartan (50 mg/kg/day), or placebo for 16 weeks. Irbesartan and captopril significantly reduced systolic pressure and produced similar rightward shifts in the angiotensin I dose-response curve. Renal renin gene expression was increased 8.6-fold by irbesartan and 17.7-fold by captopril. The only effect on echocardiographic findings was a similar decrease in aortic peak velocity, an index of systolic function, by both treatments. Early markers of cardiac hypertrophy were significantly attenuated by both drugs. Both drugs produced marked and equivalent reductions in left ventricular atrial natriuretic peptide (ANP) messenger RNA (mRNA) levels compared with controls. This decrease in ANP gene expression was accompanied by a decrease in plasma ANP concentration in the treatment groups. The shift from V1 to V3 myosin isozymes was similarly decreased in both treatment groups, compared with controls. These data suggest that captopril and irbesartan are similarly effective in controlling expression of genes associated with ventricular hypertrophy in heart failure-prone SHHF/Mcc-fa(cp) rat.
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PMID:Comparison of irbesartan with captopril effects on cardiac hypertrophy and gene expression in heart failure-prone male SHHF/Mcc-fa(cp) rats. 1006 82

Angiotensin-converting enzyme (ACE) inhibitors are established as first-line therapy in chronic heart failure (CHF). However, little is known about the dosage-plasma-level relationship of ACE inhibitors in CHF and its relation to drug-induced adverse effects. We investigated 45 patients (age 55 +/- 10 years) with stable CHF who presented with a maintenance dosage of enalapril of either 5 mg b.i.d. (E10, n = 16), 10 mg b.i.d. (E20, n = 18), or 20 mg b.i.d. (E40, n = 11). This dosage was changed three times to treat all patients with lower, higher, and, finally, the initial dosage for 4 weeks each. Patients were examined clinically, by questionnaire, and by spiroergometry. In addition, neurohormones (atrial and brain natriuretic peptide and norepinephrine), enalaprilat trough levels, and serum potassium and creatinine were measured. Enalaprilat trough levels differed significantly between the three groups at study entry but also varied markedly within each group. In addition to the dose of enalapril, serum creatinine, severity of CHF, basal metabolic rate, and body weight significantly influenced enalaprilat trough levels (R2 =.84, p <.001). Within-patient comparisons revealed that serum creatinine (107 +/- 26 versus 102 +/- 20 micromol/liter) and potassium (3.8 +/- 0.4 versus 3.7 +/- 0. 3mmol/liter) were higher, cough was more common (scored on a scale of 0-8: 1.7 +/- 2.1 versus 1.4 +/- 1.8), and blood pressure was lower (systolic, 112 +/- 14 versus 117 +/- 13 mm Hg; diastolic, 66 +/- 9 versus 69 +/- 11 mm Hg) on the highest than on the lowest enalaprilat trough level (all p <.05). Highly variable enalaprilat trough levels and the fact that adverse effects were more common on high enalaprilat trough levels provide a rationale for individually adjusting ACE-inhibitor dose in case of adverse effects.
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PMID:Plasma levels of enalaprilat in chronic therapy of heart failure: relationship to adverse events. 1008 51

The purpose of this review is to examine the potential contribution of arrhythmia to the occurrence of sudden death in dilated cardiomyopathy (DCM) and to discuss current treatment options. We performed a search of the MEDLINE database from 1985 to the present and the reference citations of selected articles pertaining to the prognostic significance, management, and pathophysiology of arrhythmias in DCM. A large proportion of patients with DCM die suddenly, most secondary to ventricular arrhythmia and a smaller proportion due to bradyarrhythmia. The presence and severity of ventricular ectopy may predict risk for sudden death, but the role of electrophysiologic study and signal-averaged electrocardiography in further risk stratifying patients remains uncertain. Abnormalities of the autonomic nervous system and renin-angiotensin-aldosterone axis appear to promote the occurrence of ventricular arrhythmias. Angiotensin-converting enzyme inhibitors improve overall mortality in congestive heart failure, and the use of direct angiotensin-receptor antagonists is currently being studied. In addition, beta-receptor antagonists appear to improve morbidity and may prove to improve mortality in heart failure as well. Other interventions still under investigation include amiodarone and the implantable cardioverter-defibrillator. The underlying pathophysiology of sudden death in DCM involves primarily ventricular tachyarrhythmia. Angiotensin-converting enzyme inhibitors remain a mainstay of improving overall mortality, while further study on the roles for newer drugs and devices is ongoing.
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PMID:Sudden death in dilated cardiomyopathy. 1019 36

Angiotensin-converting enzyme (ACE) inhibitors play an important role in protecting various organs in patients with congestive heart failure. The mechanisms of action of ACE inhibitors in congestive heart failure are multiple and may involve important effects on endothelial function in addition to the well known hemodynamic and neurohormonal effects. Skeletal muscle fatigue can play an important role in the pathophysiology of congestive heart failure, and only aggressive treatment with ACE inhibitors and exercise training can improve exercise tolerance and reduce the risk of further deterioration of cardiac function. ACE inhibitors should be introduced with caution in patients with severe heart failure and hypotension to prevent renal dysfunction. Unlike some other ACE inhibitors, perindopril seems to cause no first dose hypotension. It also appears to have a neutral effect on renal function in patients with severe congestive heart failure.
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PMID:Angiotensin-converting enzyme inhibitors and end-organ damage in heart failure. 1035 Jun 88

Angiotensin-converting enzyme (ACE) inhibitors play an important role in protecting various organs in patients with congestive heart failure. The mechanisms of action of ACE inhibitors in congestive heart failure are multiple and may involve important effects on endothelial function in addition to the well known hemodynamic and neurohormonal effects. Skeletal muscle fatigue can play an important role in the pathophysiology of congestive heart failure, and only aggressive treatment with ACE inhibitors and exercise training can improve exercise tolerance and reduce the risk of further deterioration of cardiac function. ACE inhibitors should be introduced with caution in patients with severe heart failure and hypotension to prevent renal dysfunction. Unlike some other ACE inhibitors, perindopril seems to cause no first dose hypotension. It also appears to have a neutral effect on renal function in patients with severe congestive heart failure.
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PMID:Angiotensin-converting enzyme inhibitors and end-organ damage in heart failure. 1038 Jun 88


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