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)

Angiotensin-converting enzyme (ACE) is a widely distributed dipeptidyl carboxydipeptidase. Using computer analysis of the binding of radiolabeled ACE inhibitors, we have mapped the distribution of ACE in normal animals and in models of disease, and have studied the tissue effects of ACE inhibitors. In the myocardium, ACE is located in vascular and valvular structures as well as in the atria and ventricles. Its concentration is increased in myocardial hypertrophy in the infarct model of heart failure. Chronic ACE-inhibitor therapy prevents myocardial hypertrophy. In the brain, ACE is localized in multiple specific sites where its role is unknown. Following oral ACE-inhibitor treatment, effects are restricted predominantly to areas devoid of blood-brain barrier. Early studies suggest ACE inhibitors enhance cognition. In the testis, ACE is located in the seminiferous tubules where its function is unknown. It is not inhibited following oral ACE-inhibitor treatment. In the kidney and gastrointestinal tract, ACE is in high concentration in the epithelial brush border where its function is unknown. In clinical use ACE inhibitors primarily affect the cardiovascular system. With pharmacological developments, ACE inhibitors targeted for specific organs may have effects predominantly in the brain, heart, reproductive system, or gastrointestinal tract.
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PMID:Angiotensin-converting enzyme inhibition: prospects for the future. 172

Angiotensin-converting enzyme (ACE) inhibition slowed the progression of congestive heart failure (CHF) in 170 patients who were randomly assigned to either captopril or placebo in the Munich Mild Heart Failure Trial. The two major end points were progression from New York Heart Association (NYHA) functional classes I, II, or III to class IV, despite optimal, adjusted standard therapy, and death due to CHF. The relative risk for progressive CHF with captopril therapy was 0.34 (95% confidence interval = 0.17-0.68; p = 0.01). A total of 52 prerandomization variables were tested to determine their contribution to disease progression. Logistic regression analysis revealed 5 independent risk factors for progressive CHF: NYHA class, left ventricular end-systolic diameter, need for diuretic, age, and cardiothoracic ratio. The presence of greater than 2 of these risk factors increased the odds ratio for progression to 8.13 (p less than 0.001) compared with the presence of 0-2 risk factors. However, the effectiveness of captopril in preventing progression was higher within the subgroup of patients who had less severe CHF: the odds ratio was 0.12 (95% confidence interval = 0.03-0.45; p less than 0.01) for patients in NYHA class I or II on captopril and was 0.83 for those in class III. We conclude that the severity of CHF, as represented by the above-defined risk factors, is directly related to the likelihood for the development of progressive heart failure. However, the less severe the heart failure, the more effective the treatment with captopril will be in preventing disease progression. Thus, ACE inhibition has considerable potential for improving the prognosis of patients with mild heart failure.
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PMID:Influence of severity of heart failure on the efficacy of angiotensin-converting enzyme inhibition. 174 16

It is clearly settled that the management of overt heart failure offers poor prognostic impact due to the advanced setting of the disease. Relief of symptoms, objective benefits, as testified by short-term hemodynamic improvements, are as a matter of fact not reliable prognostic markers. Myocardial dysfunction starts early in the natural history of many cardiac diseases, and runs through the steps of progressive wall remodeling, witnessed by quantitative and qualitative changes in cells, interstitium and connective tissue. Experimental studies offered keys to interventions modulated to oppose the pathophysiological changes present in early myocardial dysfunction. At present, medical therapy has made great strides in testing early myocardial dysfunction. Angiotensin-converting enzyme inhibitors, which retard ventricular dilatation and thus may lower myocardial oxygen consumption requirements seem to offer a unique prognostic profile. Preliminary pilot studies on them and some of many large-scale multicentre trials still in progress reached evidence that this class of drugs is by this time a cornerstone of medical therapy, useful to lower cardiac events-rate in patients with heart failure.
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PMID:[The effects of pharmacological treatment in asymptomatic left ventricular dysfunction]. 184 2

Angiotensin-converting enzyme inhibitors suppress plasma concentrations of the sodium retaining hormones angiotensin II and aldosterone. This action should potentiate the natriuretic and diuretic effects of loop diuretics. Some studies indicate, however, that the introduction of angiotensin-converting enzyme inhibitors for the treatment of cardiac failure is associated with transient weight gain and the development of oedema. We have compared the natriuretic and diuretic response to intravenous frusemide 40 mg alone with the natriuretic and diuretic response to intravenous frusemide 40 mg following the administration of a single dose of captopril in 12 supine male patients with stable chronic cardiac failure. Captopril lowered the 4 h diuretic response to frusemide from 1160 (60) to 685 (77) ml (P less than 0.05) and the natriuretic response from 120 (9.6) to 68 (11.7) mmol (P less than 0.05). Creatinine clearance fell after captopril from 91 (7.2) to 57 (7.7) ml min-1 (P less than 0.05). Systolic and diastolic blood pressures were lower after the administration of captopril but these changes were not significant. Plasma renin activity rose from 3.8 (1.04) to 12.34 (2.94) ng ml h-1 (P less than 0.05) and plasma angiotensin II was reduced from 24.9 (5.05) to 8.14 (1.8) pg ml-1 (P less than 0.05). Plasma aldosterone concentrations were not significantly lower following captopril. Angiotensin-converting enzyme inhibitors cause an acute fall in creatinine clearance which may reduce the effects of loop diuretics and attention must be paid to diuretic dosage when initiating angiotensin-converting enzyme inhibitors for the treatment of cardiac failure.
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PMID:Acute administration of captopril lowers the natriuretic and diuretic response to a loop diuretic in patients with chronic cardiac failure. 191 30

The renin-angiotensin-aldosterone system (RAAS) has been implicated in the pathogenesis of congestive heart failure (CHF). Abnormal activation of the RAAS adversely affects cardiac performance and impairs functional status, increasing both afterload and preload through direct and indirect mechanisms. Conventional first-line therapy for CHF consists of diuretics and/or digitalis. Diuretics offer rapid relief of symptoms, effective volume control, and ease of administration, but are associated with a number of disadvantages, including further activation of neurohormonal systems resulting in augmented vasoconstriction. Angiotensin-converting enzyme (ACE) inhibitors, which block the RAAS by inhibiting production of angiotensin II from angiotensin I, are emerging as the vasodilators of choice in combination with diuretics with or without concomitant digitalis. Direct comparative studies have shown that ACE inhibitors provide acute and long-term symptomatic, hemodynamic, and exercise-related benefits as well as improved functional class and, possibly, slowed progression of disease with enhanced survival in specific subgroups. Captopril was the first orally effective ACE inhibitor associated with improved exercise tolerance and functional class in large multicenter trials of patients with severe heart failure and mild to moderate heart failure. Enalapril reduced the probability of death in patients with severe heart failure in the CONSENSUS trial. The new ACE inhibitor quinapril has been shown to improve hemodynamic status both acutely and chronically and to produce dose-related improvements in exercise tolerance. ACE inhibitors have a favorable safety profile, although hypotension can occur with initial doses, particularly in volume-depleted patients or at times when excessive initial doses are administered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ACE inhibitors in the treatment of heart failure. 218 19

The increased neuroendocrine activity in patients with congestive heart failure appears to be a generalized attempt to maintain blood pressure at the expense of reduced cardiac performance and salt and water retention. It is likely that baroreceptor dysfunction contributes to increased sympathetic nervous system activity in patients with congestive heart failure. The usual tonic inhibitory messages emanating from baro- and mechanoreceptors in the great vessels and heart fail to adjust sympathetic traffic from the brain to the periphery, leading to uninhibited sympathetic tone. Arginine vasopressin and plasma renin activity may be increased secondarily; however, plasma renin activity activation could also be induced by a low-salt diet and diuretic use. Preliminary baseline data indicate that patients with left ventricular dysfunction (ejection fraction less than or equal to 35%) but no or very mild symptoms of heart failure have increased plasma levels of norepinephrine, atrial natriuretic factor and arginine vasopressin, while plasma renin activity is normal, suggesting that neuroendocrine activity contributes to the pathogenesis of congestive heart failure. Neurohormones such as angiotensin II may alter gene expression, leading to changes in the shape and size of the cell. Remodeling of the heart and blood vessels is associated with both heart failure and hypertension. Angiotensin-converting enzyme inhibitors have been demonstrated to retard or reverse the remodeling process under certain experimental conditions. Studies are currently under way to test this possibility in patients.
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PMID:Neuroendocrine activity in congestive heart failure. 222 Jun 3

Angiotensin-converting enzyme inhibitors are mixed vasodilators with a prolonged sustained effect in chronic heart failure. They also act on the reactivity of peripheral circulation, on ventricular remodelling after myocardial infarction, on myocardial hypertrophy in arterial hypertension and on ventricular hyperexcitability. They alleviate the symptoms of symptomatic heart failure, and they constitute the only treatment that has been able to improve the survival of patients with the most severe heart failure. Several studies are in progress to determine whether these drugs should be used as first-line therapy.
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PMID:[Converting enzyme inhibitors and cardiac insufficiency: current findings and perspectives]. 226 65

Angiotensin-converting enzyme (ACE) inhibitors and diuretics are known to cause hyperkalaemia. We undertook a prospective analysis over a period of six months of patients admitted under our care. Of 217 patients, 39 (18 per cent) were admitted with congestive cardiac failure/left ventricular failure. Of these 39 patients, 21 (54 per cent) were prescribed ACE inhibitors. Seven of these 21 patients subsequently developed hypokalaemia. This was irrespective of the type or dose of the diuretic but seemed to be related to the dose of the ACE inhibitor. In three cases the hypokalaemia was corrected by the addition of a potassium-sparing diuretic; in two cases a potassium supplement was added; and in the other three an increase in the dose of the ACE inhibitor for the resistant heart failure corrected the potassium deficit. This study shows that one should be alert to both hyperkalaemia and hypokalaemia when using a combination of ACE inhibitors and diuretics.
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PMID:ACE inhibitors and diuretics causing hypokalaemia. 231 35

Angiotensin-converting enzyme (ACE) inhibitors are of benefit in the management of heart failure. In some studies in patients with heart failure, a decline in renal function occurred more frequently in patients treated with enalapril maleate, a longer-acting agent, than in those treated with captopril, a shorter-acting drug. Patients experiencing a decline in renal function had a number of predisposing hormonal and hemodynamic factors. In one report, these factors included an initial fall in blood pressure that was sustained, lower cardiac output, and a relatively high fixed dose of enalapril that contributed to renal impairment. In a second study, the decline in renal function was most severe in patients with a lower systemic arterial pressure in whom glomerular filtration may have been dependent on angiotensin II. In a third study, intravascular volume depletion and an activated renin-angiotensin system led to reduced renal function. Reduction of angiotensin II level in plasma and tissues by ACE inhibitors decreases systemic vascular resistance and efferent arteriolar tone, which tends to decrease glomerular filtration rate. If compensatory increases in cardiac output are inadequate or preexisting renal impairment or volume depletion is present, renal function will deteriorate. Long-acting ACE inhibitors prolong the decreased efferent arteriolar tone and may compromise cardiac muscle response to catecholamines. The use of shorter-acting agents in patients who exhibit deterioration in renal function may be preferable.
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PMID:Renal hemodynamic consequences of angiotensin-converting enzyme inhibition in congestive heart failure. 253 12

Angiotensin-converting enzyme inhibitors are vasodilators that exert their beneficial hemodynamic effects in hypertension primarily by withdrawal of the vasoconstricting action of endogenous angiotension II. Although the magnitude of the initial decrease in vascular resistance depends on renin activity, the long-term arterial blood pressure response does not appear to be influenced by initial renin levels. Cardiac output is not significantly altered by angiotensin-converting enzyme inhibition in patients with mild-to-moderate hypertension, but a rise toward normal levels often occurs in patients with severe hypertension or heart failure. Although right and left heart filling pressures are not significantly altered, other evidence suggests that these agents increase venous capacitance. Patients with severe hypertension, for example, have shown increased forearm venous distensibility in response to angiotensin-converting enzyme inhibitors, and a decrease in the ratio of cardiopulmonary blood volume to total blood volume has been demonstrated in normotensive patients with heart failure. Several studies have shown improved renal blood flow after angiotensin-converting enzyme inhibition, suggesting that renal vascular resistance is reduced more than systemic resistance. Reflex tachycardia and other neurohumoral counterregulatory responses occur less frequently than with other vasodilators, because neither the renin-angiotensin-aldosterone nor the autonomic nervous system is activated by angiotensin-converting enzyme inhibition.
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PMID:Hemodynamic effects of angiotensin-converting enzyme inhibitors in essential hypertension: a review. 258 Jan 74


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