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

Angiotensin II causes pulmonary vasoconstriction in man and in animals, and angiotensin-converting enzyme (ACE) inhibitors have prevented the development of chronic pulmonary hypertension in animals models. Angiotensin II may contribute to lung vascular remodeling in pulmonary hypertensive disease, since cilazapril, an inhibitor of ACE, reduces pulmonary vascular medical thickening in chronically hypoxic rats with established pulmonary hypertension. Furthermore, the ACE DD genotype, which has been associated with increased circulating and tissue ACE activity, has been associated with left ventricular hypertrophy in human hypertensive disorders. The ACE DD genotype may also 'permit' a greater hypertrophic adaptation of the pressure-over-loaded right ventricle. In fact, we have shown that pulmonary hypertension patients with maintained cardiac output and less right-heart failure fall into the group with the DD genotype and that patients with a low cardiac output and more severe right-heart failure fall into the group with the non-DD genotype, supporting the hypothesis. We assessed cardiopulmonary hemodynamics in patients with primary (unexplained) pulmonary hypertension and segregated the patients based on their ACE genotype. For similar mean pulmonary artery pressures in the DD and non-DD groups, the cardiac output was substantially lower in the patients with the non-DD genotype, whereas the values for mean right atrial pressure and pulmonary vascular resistance were double when compared with the DD group. Our data show that the ACE DD genotype is prevalent in patients with severe pulmonary hypertension and is a marker of maintained right ventricular function.
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PMID:Importance of angiotensin-converting enzyme in pulmonary hypertension. 761 7

At least theoretically, ACE-inhibitors may influence each of the factors involved in the regulation of salt and water metabolism. Angiotensin II exerts an antidiuretic and antinatriuretic action on the kidney through influences on the glomerular filtration coefficient, glomerular filtration rate, mesangial tone, filtration fraction, proximal and distal tubule. Angiotensin II and renin also regulate the input of water and salt through an unequivocal dipsogenic effect. In congestive heart failure angiotensin II participates in the preservation of the glomerular filtration rate through its vasoconstrictor properties on the systemic vessels (maintenance of the perfusion and filtration pressure) as well as on the efferent arteriole (maintenance of the filtration pressure). ACE-inhibition weakens or abolishes these influences. However, two favorable mechanisms may also come into action: rise of cardiac output and improvement in renal blood flow; widening of the filtration surface and increment of the filtration coefficient. The efficacy of these factors depends on renal function, age, functional recovery of the heart, treatment with diuretics, duration of treatment with ACE-inhibitors, duration of action of the ACe-inhibitor used, blockade of the facilitating action on the adrenergic vasoconstriction, formation of vasodilating prostaglandins, reduced degradation of kinins. All these effects may account for the variable and often contradictory clinical results, in particular as concerns the relationship between ACE-inhibition and use of diuretics in congestive heart failure. This also explains the variability of efficacy (from the development of pulmonary edema and requirement of diuretics to diuretic withdrawal and clinical improvement) of the ACE-inhibitors as monotherapy in mild to moderate heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[ACE-inhibitors and water metabolism in heart failure]. 763 56

The renin-angiotensin system (RAS) participates in both cardiovascular homeostasis and diseases. Angiotensin converting enzyme (ACE) inhibitors have been used very successfully in the treatment of hypertension and heart failure. The therapeutic effectiveness of these drugs has been ascribed to their action in limiting the activity of the RAS and suggests that other pharmacological mechanisms that block this system, such as angiotensin II receptor inhibitors, could also be of benefit. Some properties of angiotensin II receptor inhibitors offer potential advantages over ACE-inhibitors. ACE acts on other substrates in addition to angiotensin I (i.e. bradykinin) so that more specific inhibition of the RAS can be achieved with selective angiotensin II antagonists. Data on the existence of both circulating and tissue RAS have been reported, and non-ACE pathways for angiotensin II production have also been described. So, by inhibiting the interaction of the biological active peptide at its receptor level, an angiotensin II receptor antagonist will inhibit the RAS independently of the source or route of angiotensin II synthesis. Peptide angiotensin II antagonists were first reported 20 years ago and the best studied was saralasine; they are potent and selective blockers of angiotensin II responses, but their lack of oral activity, short duration of action and the concomitant partial agonistic activity limited their clinical use. Now are available nonpeptide angiotensin II antagonists with attributes appropriate for clinical development. The preliminary evaluation of these new selective nonpeptide angiotensin II antagonists show their potential therapeutic role in many cardiovascular diseases in which the RAS is involved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical pharmacology of angiotensin II antagonists]. 763 4

Angiotensin converting enzyme (ACE) inhibitors have been shown to improve morbidity and mortality in patients with heart failure. However, despite the demonstrated clinical benefits many physicians are reluctant to prescribe ACE-inhibitors to the mostly elderly heart failure patients due to concern for side effects which may be related to ACE-inhibitor-induced bradykinin accumulation. Angiotensin II receptor antagonists may provide more effective blockade of the renin-angiotensin-aldosterone system without causing bradykinin accumulation and thus associated side effects. The potential benefits of treating heart failure patients with an angiotensin II receptor antagonist instead of or in addition to an ACE-inhibitor are discussed.
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PMID:Theoretical basis for the use of angiotensin II antagonists in the treatment of heart failure. 763 6

The renin-angiotensin system is critical for regulating extracellular fluid volume and blood pressure. Angiotensin II, the active peptide hormone produced by the renin enzymatic cascade, sustains vascular volume and blood pressure by constricting vessels, stimulating adrenal aldosterone secretion, increasing renal tubular sodium absorption, activating the sympathetic nervous system, and increasing cardiac contractility. These actions are a disability in the pathophysiologic states of hypertension and congestive heart failure (CHF), however, since reactive increases in renal renin and angiotensin II stimulate sympathetic activity and renal sodium retention, leading consequently to circulatory volume over-load. The actions of angiotensin II are mediated by its interactions with specific cell-surface angiotensin II receptors, namely, AT1 and AT2; most cardiovascular actions of angiotensin II come from its interaction with the AT1 receptor. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II-receptor blockers antagonize the actions of the renin-angiotensin axis, neutralizing its effects on hypertension and heart failure. Losartan is the first oral, nonpeptide, selective AT1-receptor blocker to be approved. Clinical trials show it to be effective and well tolerated as therapy for hypertension and CHF. Data obtained thus far suggest ACE inhibitors and AT1-receptor blockers have similar efficacy for treating these conditions, but the receptor blockers appear to produce fewer adverse effects. Whether the sustained increase in angiotensin II concentrations after AT1-receptor antagonism produces deleterious effects is not known. The concern is that these high levels may stimulate unblocked AT2 receptor; the effect of that stimulation may not be important, however.
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PMID:Angiotensin receptors: physiology and pharmacology. 763 61

Endothelin is a powerful vasoconstrictor that may be partly responsible for the increases in venous and arterial tone characteristic of heart failure. The release of endothelin from endothelial cells in culture is stimulated by angiotensin II. We investigated the relationship between plasma concentrations of immuno reactive endothelin-1 and angiotensin II in 25 patients with heart failure and eight with ischaemic heart disease but normal left ventricular function. Plasma concentrations of endothelin and angiotensin II were correlated (Spearman rank correlation coefficient of 0.72; P < 0.0001) in patients with heart disease. Plasma concentrations of angiotensin II and endothelin were higher in those patients with heart failure. Angiotensin II was infused over a 3 h period in eight healthy volunteers. Infusion of angiotensin II increased plasma concentrations of angiotensin II to levels greater than those usually found in patients with severe heart failure but induced only a modest rise in plasma concentrations of immunoreactive endothelin-1 (0.77 +/- 0.16 to 1.03 +/- 0.03 pmol.l-1, P < 0.02). Increased plasma concentrations of angiotensin II and endothelin-1 both appear to reflect the presence and severity of heart failure. Although a significant correlation exists between plasma concentrations of angiotensin II and endothelin in patients with heart failure, the relationship may not be causal.
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PMID:Elevated plasma endothelin concentrations in heart failure; an effect of angiotensin II? 769 33

Angiotensin II (Ang II) receptor heterogeneity is currently defined by the new subtype-selective agents, losartan (AT1) and PD123177 (AT2). Although both subtypes have been cloned and sequenced, only the AT1 receptor has been shown to have an important physiological or pathophysiological role. AT1 and AT2 receptors are found in both normal and failing cardiac tissue. They are found on myocytes, endothelial cells, fibroblasts, coronary arterial smooth muscle cells, and peripheral sympathetic nerves. The AT1 receptors mediate virtually all of the effects of Ang II in myocytes even though cardiac tissue may contain over 50% AT2 sites. In endothelial cells, functional responses are predominately AT1. In fibroblasts, preliminary data suggest that AT2 receptors may be involved in collagen synthesis. In isolated tissue, Ang II has a limited positive inotropic effect in atrial, but not in ventricular tissue, which is blocked by losartan. Ang II may also have a tonic effect on coronary artery resistance as angiotensin inhibitors can increase coronary flow. Both ACE (Ang II synthesis) inhibitors and Ang II receptor antagonists produce beneficial effects in experimental models of heart failure, suggesting Ang II is an important mediator of heart failure. Because ACE inhibitors also potentiate bradykinin and are non-specific inhibitors of Ang II synthesis (availability of Ang II to both receptor subtypes) some differences can be anticipated. At the present time, however, the beneficial role of bradykinin is controversial and the predominant functional Ang II receptor in the heart and other tissues is the AT1 subtype.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin II receptor subtypes: selective antagonists and functional correlates. 771 19

Angiotensin converting enzyme (ACE) inhibitors are now widely used for the treatment of hypertension and heart failure. They are of particular value in treating hypertensive patients with left ventricular dysfunction, and in diabetics where they have been shown to delay the progression of diabetic nephropathy. Differences in the metabolism, pharmacokinetics, and pharmacodynamics between the various ACE inhibitors generally do not translate into significant clinical differences in the majority of patients. However, fosinopril may be the preferred ACE inhibitor in patients with significant renal dysfunction because of a reduced requirement for dosage reduction. The duration of action of ACE inhibitors is determined by two properties, the plasma half-life and the affinity of binding to tissue ACE. All of the ACE inhibitors (with the possible exception of captopril) can provide satisfactory 24-hour blood pressure control in the majority of patients with mild to moderate hypertension when given once daily. Lisinopril provides consistently better 24-hour control of blood pressure than either captopril or enalapril. Evidence for superior 24-hour blood pressure control over enalapril has not been as well established for the other ACE inhibitors. Captopril may be preferred for initiating therapy in patients with severe heart failure who are at risk of first dose hypertension because of its rapid onset of action and relatively short duration of action. There is evidence, however, that perindopril may have a low risk of first dose hypertension in heart failure because of its gradual onset of action. Long-acting ACE inhibitors may be preferable for chronic therapy of heart failure. All of the ACE inhibitors have a low incidence of adverse effects in both young and elderly patients, and there is no convincing evidence of differences in tolerability between the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Critical assessment of ACE inhibitors. Part 2. 777 72

Left ventricular hypertrophy (LVH) is a common consequence of hypertension, and an independent risk factor for cardiovascular morbidity and mortality. The presence and severity of LVH is best determined by echocardiography and expressed as left ventricular mass index or left ventricular wall thickness. Pathological LVH, in response to pressure or volume load on the heart, is characterised by myocyte hypertrophy and hypertrophy/hyperplasia of nonmyocyte cells within the myocardium. Angiotensin II and aldosterone are promoters of increased fibroblast activity and a significant increase in collagen fibres in the myocardium. Early diagnosis and treatment of hypertension has significantly decreased the incidence of LVH and subsequent heart failure in many countries, but the choice of antihypertensive therapy alters the rate of reversal of LVH and the subsequent development of heart failure. Angiotensin converting enzyme (ACE) inhibitors, beta-blockers and calcium channel blockers produce the most rapid reversal of hypertrophy. Meta-analysis of these many small trials suggests an advantage of ACE inhibitors over other groups of antihypertensive agents.
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PMID:Hypertrophy to failure. 780 8

The introduction of new drugs, and a re-evaluation of older drugs, have radically changed the pharmacological management of heart failure. Angiotensin converting enzyme (ACE) inhibitors, digitalis, diuretics and the combination of nitrates and hydralazine are now used. The first Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS I) and the second Vasodilator therapy in Heart Failure Trial (V-HeFT II) have demonstrated that patients with severe or advanced heart failure should be treated with ACE inhibitors, digitalis and diuretics (other vasodilators can be used if ACE inhibitors are contraindicated) to improve symptoms and duration of life. The Studies Of Left Ventricular Dysfunction (SOLVD) and the Munich Heart Failure trial have shown that patients with mild heart failure should be treated with ACE inhibitors. However, data from several large clinical registries suggest that only 40% of patients with heart failure are being given ACE inhibitors perhaps through fear of serious renal damage or hypotension; these fears are unfounded. Patients with anterior myocardial infarcts and reduced left ventricular function also benefit from ACE inhibitors. The fourth International Study of Infarct Survival (ISIS 4) and results from the Gruppo Italiano per Io Studio della Sopravvivenza nell'Infarto miocardico 3 (GISSI 3) have indicated that patients with acute myocardial infarction benefit from early ACE inhibitor therapy and that survival is increased. Heart failure treatment can be optimized by establishing a disease etiology and stressing the need to restrict dietary sodium. ACE inhibitors should be used for depressed left systolic ventricular function, including patients in New York Heart Association class I heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Optimizing the treatment of heart failure. 782 70


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