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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ACE-inhibitors improve symptoms and prognosis in patients with heart failure. The V-Heft II trial has demonstrated that the beneficial effect of these agents is superior to unspecific vasodilators. Besides sustained arterial and venous vasodilation the inhibition of the neurohumoral axis is thought to play an important role. Angiotensin II and catecholamines not only exert vasoconstrictor effects, but might also contribute to vascular and myocardial growth. Thus, it may not be surprising that the beneficial effects of ACE inhibitors in heart failure only emerge during long-term therapy rather than after short-term administration. It has been shown that these agents improve blood flow to skeletal muscle during exercise after chronic therapy (not acutely), and there is some preliminary evidence that improvement of endothelial function might be involved in this effect, i.e., by reducing the degradation of bradykinin, an endothelial vasodilator. ACE inhibitors reduce LV hypertrophy, an important risk factor for cardiovascular disease and prognosis. Moreover, there is experimental evidence that ACE inhibitors can prevent and even reverse interstitial fibrosis in the left ventricle. Although the plasma renin activity may be normal in patients with chronic heart failure, recent data using polymerase chain reaction indicate that the tissue cardiac renin angiotensin system is activated in the failing human heart as assessed by measurements of angiotensin converting enzyme mRNA and angiotensinogen mRNA which may be an important target for ACE-inhibition.
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PMID:[The value of ACE inhibitors in heart failure (mechanism of action)]. 129 Mar 8

Inhibition of intrarenal neutral endopeptidase 24:11 (NEP) increases the natriuretic response to infused atrial natriuretic peptide (ANP). In various models of canine heart failure, angiotensin and kinins have been shown to modulate ANP and (or) NEP activity. In the present study, we examined possible modulators of NEP activity in normal dogs by infusing various agents into the left renal artery (or by denervating the left kidney) and comparing the response of this kidney with that of the contralateral one following the combined intravenous infusion of Squibb 28603 (a potent NEP inhibitor) and ANP (75 ng.kg-1.min-1). Four dogs received angiotensin (1.5 ng.kg-1.min-1) into the left renal artery, 8 dogs received saralasin (5 micrograms/min), 5 dogs received noradrenaline (2 micrograms/min), and 6 dogs received bradykinin (3 micrograms/min). Five dogs underwent left renal denervation. Angiotensin inhibited sodium excretion following the NEP inhibitor alone and after the NEP inhibitor plus ANP. Saralasin augmented the natriuretic response. None of the other protocols influenced sodium excretion. We conclude that angiotensin may modulate either the enzymatic degradation of ANP or influence its renal tubular effects.
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PMID:Modification of the renal response to endopeptidase inhibition and atrial natriuretic peptide infusion in normal dogs. 130 Dec 33

In recent years, captopril has attracted considerable clinical attention as an agent for use in treating heart failure. We administered 15 mg/kg of captopril or 1.5 mg/kg of enalapril to 5-week-old J-2-N cardiomyopathic hamsters for 10 or 15 weeks, and investigated the roles of the renin-angiotensin-aldosterone and kallikrein-kinin systems in the onset and progress of cardiomyopathy. In the untreated group, serum creatine kinase levels increased in accordance with the progression of cardiomyopathy, but this increase was markedly inhibited by the administration of captopril. The rise in serum aldolase levels was similarly inhibited. Serum malondialdehyde levels were significantly reduced by the administration of captopril. ECG findings and the ventricular myosin isoenzyme pattern were also markedly improved by captopril. The improvement in all these parameters was less with enalapril. These differences between captopril and enalapril suggest that increases in tissue bradykinin and vasodilatory prostaglandins may play an important role in the beneficial effects of captopril.
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PMID:The effects of angiotensin converting enzyme inhibitors and the role of the renin-angiotensin-aldosterone system in J-2-N cardiomyopathic hamsters. 153 90

ACE inhibitors (ACEIs) have now been shown to improve symptoms and survival in patients with mild, moderate and severe chronic heart failure. Their mechanism of action is thought to be a combination of RAAS suppression and augmentation of bradykinin and prostaglandins. Although ACE inhibitors improve hemodynamics post myocardial infarction, we do not yet have consistent data on their effects on symptoms or survival in these particular patients. One other potential benefit is their effects on reperfusion injury and free radicals. As yet only minor differences have been found to exist between different ACEIs but increasing attention is now being focussed in this direction.
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PMID:The clinical pharmacology of angiotensin converting enzyme inhibitors in chronic heart failure. 164 5

In chronic heart failure, neurohumoral mechanisms play an important role in the regulation of cardiac performance directly, by influencing systolic and diastolic function of the myocardium, and indirectly, by modulating pre- and afterload. The important vasoconstrictor, fluid and sodium retaining factors are the renin-angiotensin-aldosterone system, sympathetic nerve activity and vasopressin; the vasodilator, volume and sodium eliminating factors are atrial natriuretic peptide, vasodilator prostaglandins, such as prostacyclin and prostaglandin E2, dopamine, bradykinin and, possibly, endothelium-derived relaxing factor and vasoactive intestinal peptide. There is evidence from experimental and clinical studies that sympathetic nerve activity is stimulated in the early phase of the disease, as is the secretion of atrial natriuretic peptide, which increases in proportion to an increased preload. In early or mild heart failure, atrial natriuretic peptide suppresses the activity of the renin-angiotensin-aldosterone system, may prevent an increase in peripheral vascular resistance and preserves renal blood flow. In more severe heart failure, the renin-angiotensin-aldosterone system is activated, leading to an increase of peripheral and renal vascular resistance and fluid and sodium retention. This is associated with an increased production of vasodilator prostaglandins. In severe heart failure, mostly in connection with hyponatraemia, a non-osmolar inappropriately high secretion of vasopressin can be demonstrated. These findings suggest that early therapeutic intervention to suppress unfavourable neurohumoral mechanisms or to support protective factors, such as atrial natriuretic peptide, may be of particular importance in the treatment of congestive heart failure, delaying progression of the disease, which would improve survival.
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PMID:Hormones in heart failure--regulation and counterregulation. 183 97

In chronic heart failure, neurohumoral mechanisms play an important role in the regulation of cardiac performance by direct influences on systolic and diastolic function of the myocardium, and indirectly, by modulation of pre- and afterload. Important vasoconstrictor, fluid- and sodium-retaining factors are the renin-angiotensin-aldosterone system, sympathetic nerve activity, and vasopressin; vasodilator, volume, and sodium-eliminating factors are atrial natriuretic peptide, vasodilator prostaglandins like prostacyclin and prostaglandin E2, dopamine, bradykinin, and possibly, endothelial derived relaxing factor (EDRF). There is evidence from experimental and clinical studies that the sympathetic nerve activity is stimulated in the early phase of the disease, as well as is the secretion of atrial natriuretic peptide which increases in relation to a rise in preload. In early or mild heart failure, atrial natriuretic peptide suppresses the activity of the renin-angiotensin-aldosterone system, which may prevent an increase in peripheral vascular resistance and preserve renal blood flow. In more severe heart failure, the renin-angiotensin-aldosterone system is activated, leading to an increase of peripheral and renal vascular resistance and fluid and sodium retention. This is associated with an increased production of vasodilator prostaglandins. In severe heart failure, mostly in connection with hyponatremia, a nonosmolar, inappropriately high secretion of vasopressin can be demonstrated. These findings suggest that early interventions in order to suppress unfavorable neurohumoral mechanisms or to support protective factors like atrial natriuretic peptide may be of particular importance in the treatment of congestive heart failure with the aim of a retardation of the progression of the disease, which would result in an improvement of survival.
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PMID:Role of neuroendocrine mechanisms in the pathogenesis of heart failure. 183 44

ACE inhibition may be useful in several manifestations of ischaemic heart disease, such as heart failure due to ischaemic cardiomyopathy. Recent evidence suggests that these effects may also be present in normotensive patients with ischaemic heart disease without heart failure. Theoretically, converting-enzyme inhibition, through coronary and systemic vasodilating effects and negative inotropic properties, should have a favourable effect on the myocardial oxygen supply/demand ratio and, hence, affect the incidence and severity of myocardial ischaemia. It is doubtful, however, whether these cardiac and extracardiac properties of ACE inhibitors really underlie its potential antiischaemic effects, at least in the average patient with ischaemic heart disease without concomitant heart failure and hypertension. Recent animal and human studies indicate that converting-enzyme inhibitors may modulate myocardial ischaemia by reducing ischaemia-induced circulating neurohumoral activation. It has been shown that, depending on the severity of ischaemia, the circulating renin-angiotensin system may become activated together with an increase in circulating catecholamine levels. ACE inhibition suppresses this neuroendocrine stimulation during ischaemia and modulates subsequent systemic and, presumably, also coronary vasoconstriction. In addition to these effects on circulating neurohormones, ACE inhibition could affect myocardial ischaemia through a number of local actions, e.g. modulation of tissue (cardiac) angiotensin II formation and bradykinin breakdown, stimulation of prostaglandin synthesis and, in the use of sulphydryl compounds, by affecting EDRF formation. Whether ACE inhibitors have clear antiischaemic effects in all clinical conditions is uncertain. Their efficacy to limit exercise-induced ischaemia has been questioned. In contrast, pacing-induced ischaemia in patients at rest is clearly prevented by ACE inhibition. This differential effect may be related to a more pronounced difference in circulating neurohormones during exercise per se. It also suggests that ACE inhibitors may be particularly useful as (additional) antiischaemic therapy in patients with angina at rest, e.g. unstable angina and the acute phase of myocardial infarction.
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PMID:Neurohumoral activation during acute myocardial ischaemia. Effects of ACE inhibition. 197 98

The role of ACE-inhibition for the treatment of congestive heart failure has been established over the last decade. In patients with moderate and severe congestive heart failure long-term beneficial effects on symptoms may be achieved in 60-70%. Mortality is significantly improved in patients with congestive heart failure functional class NYHA IV. Therefore, ACE-inhibitors are superior to other vasodilators. Hypotension represents an important side effect of ACE-inhibitors. It is predominantly due to either inhibition of systemic and/or local angiotensin II formation or to reduce degradation of bradykinin. If the activity of the renin-angiotensin system is stimulated, as in severe congestive heart failure and/or by diuretic pretreatment, the risk for the occurrence of hypotension is therefore increased. With respect to these risk factors, small doses of ACE-inhibitors should be administered initially, e.g. captopril 6.25 mg or enalapril, 2.5 mg. Recently, two large trials demonstrated the safety of enalapril, a long-acting ACE-inhibitor, regarding the occurrence of hypotension in patients with congestive heart failure. The overall incidence of hypotension is about 2-4% in mild to moderate and about 5-8% in severe heart failure. Reduction of the dosage of the ACE-inhibitor or the diuretic drug usually results in normalization of blood pressure, allowing continuation of therapy with ACE-inhibitors.
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PMID:[Side effects of vasodilator therapy in heart failure: risk of hypotension with ACE inhibitors]. 202 38

It is not completely clear if the renal sympathetic nerves are essential for normal renal function, however, it has been reasonably well established that the renal nerves can influence renal function under experimental conditions. These influences are manifested as changes in sodium excretion, urine flow, renin release, renal blood flow and glomerular filtration rate. Under conditions of stress the renal nerves can have powerful influences on renal function and, as a result, on systemic hemodynamics. Because renal sympathetic outflow is under central control, the reflex modulation of renal nerve activity is an extremely important factor in the control of salt and water balance. We have shown that cardiac and arterial baroreflex control of renal nerve activity is abnormal in chronic congestive heart failure. The mechanisms for this abnormality can reside in any arm of the reflex arc. The evidence from this and other laboratories has clearly implicated the afferent limb of these reflexes as being abnormal. Experiments done in anesthetized dogs with pacing induced heart failure have indicated that the central component of these reflexes are probably normal. The experiments described above cannot differentiate between abnormal afferent mechanisms and abnormal end organ responses to renal nerve stimulation. Several humoral mechanisms may be operative in heart failure to modulate renal nerve activity. These include bradykinin, prostaglandins and the renin-angiotensin aldosterone axis. Future work should be directed towards a further understanding of the role played by these and other humoral factors in the control of renal sympathetic outflow in heart failure.
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PMID:Reflex control of renal sympathetic nervous activity in heart failure. 206 56

Apart from their established use in the treatment of hypertension and heart failure, ACE inhibitors have been suggested to exert anti-ischemic effects. This article reviews the mechanisms of systemic and intracardiac angiotensin formation, as well as its interaction with the bradykinin, the prostaglandin, and the sympathetic nervous system. While high doses of angiotensin can precipitate myocardial ischemia. experimental data on a potential beneficial effect of ACE inhibitors on ischemic myocardial blood flow and function are inconsistent and controversial. Pooling the few available clinical data, several ACE inhibitors may attenuate myocardial ischemia at rest and during exercise. However, a significant fraction of patients does not benefit or even deteriorates. Recent experimental studies suggest a beneficial role of ACE inhibitors in attenuating reperfusion arrhythmias and postinfarction left ventricular remodeling. Unless the mechanisms and determinants of potential anti-ischemic actions of ACE inhibitors can be better defined, their use for treatment of myocardial ischemia cannot be recommended at present.
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PMID:ACE inhibitors for the treatment of myocardial ischemia? 227 72


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