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

For almost 40 years since its discovery in 1953, the mineralocorticoid hormone, aldosterone, was considered to affect blood volume, and thus blood pressure, by its action to retain sodium at epithelial tissues. Over the past decade, direct effects of aldosterone on the heart and blood vessels, and on the cerebral control of blood pressure, have been established in experimental animals. Simultaneously, the incidence of primary aldosteronism in essential hypertension is now acknowledged to be 10-20%, rather than <or= 1%, underscoring a previously unrecognized role for aldosterone in hypertension. The 30% improvement in mortality (and 35% in morbidity) seen in the RALES trial with the addition of low-dose spironolactone to best practice therapy in moderate to severe heart failure, similarly points to an unrecognized role for aldosterone in the pathophysiology of heart failure. Currently, both experimental and clinical studies are directed towards establishing the mechanisms involved in these pathophysiological effects of aldosterone in the cardiovascular system, and of the role of mineralocorticoid receptor antagonists in offsetting or blocking such effects. A brief account of the current state of these mechanisms in at a cellular and tissue level forms the basis of this review.
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PMID:Mineralocorticoid receptors and pathophysiological roles for aldosterone in the cardiovascular system. 1217 1

Heart failure is a major health problem of epidemic proportions. Irrespective of its etiologic origins, a dysfunction of this normally efficient muscular pump is associated with systemic consequences, a progressive downhill clinical course and poor prognosis. Ventricular dysfunction is ultimately accompanied by neurohormonal system activation that accounts for: the congestive heart failure syndrome; an induction of oxi/nitrosative stress; adverse vascular remodeling; and activation of the immune system that contributes to a wasting syndrome known as cardiac cachexia. Circulating effector hormones of the renin-angiotensin-aldosterone system are an integral feature of this neurohormonal activation; they have systemic consequences. Insights into the pathophysiology of heart failure will identify improved methods of prevention, including biomarkers to aid in its detection and identification of risk, and to the development of specific drug targets. Herein we address one aspect of the neurohormonal profile of heart failure, namely that related to aldosteronism. Our focus is directed at the link between aldosteronism and its adverse influence on coronary vasculature structure, a proinflammatory/fibrogenic cardiac phenotype, which is based on an immunostimulatory state that includes activated peripheral blood mononuclear cells.
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PMID:Aldosteronism in heart failure: a proinflammatory/fibrogenic cardiac phenotype. Search for biomarkers and potential drug targets. 1286 65

Voltage-operated calcium channels play a crucial role in signal transduction in many excitable and non-excitable cell types. While a rapid modulation of their activity by hormone-activated kinases and/or G proteins has been recognized for a long time, a sustained control of their expression level has been only recently demonstrated. In adrenal H295R cells, for example, aldosterone treatment selectively increased low threshold T-type calcium current density without affecting L-type currents. Antagonizing the mineralocorticoid receptor (MR) with spironolactone prevented aldosterone action on T-type currents. By RT-PCR, we detected in these cells the presence of two different isoforms of L-type channels, alpha(1)C and alpha(1)D, and one isoform of T channel, alpha(1)H. A second T channel isoform (alpha(1)G) was also observed under particular culture conditions. Quantification of the specific messenger RNA by real time RT-PCR allowed us to show a 40% increase of the alpha1H messenger levels upon aldosterone treatment (alpha(1)G was insensitive), a response that was also completely prevented by spironolactone. Because T-type, but not L-type channel activity is linked to steroidogenesis, this modulation represents a positive, intracrine feed back mechanism exerted by aldosterone on its own production. Aldosterone has been also implicated in the pathogenesis and progression of ventricular hypertrophy and heart failure independently of its action on arterial blood pressure. We have observed that, in rat neonatal cardiomyocytes, aldosterone increases (by two-fold) L-type calcium current amplitude in ventricular but not in atrial cells. No significant effect of aldosterone could be detected on T-type currents, that were much smaller than L-type currents in these cells. However, aldosterone exerted opposite effects on T channel isoform expression, increasing alpha(1)H and decreasing alpha(1)G. Although the functional role of T channels is still poorly defined in ventricular cardiomyocytes, an overexpression of alpha(1)H could be partially responsible for the arrhythmias linked to hyperaldosteronism.Finally, T channels also appear to be involved in the neuroendocrine differentiation of prostate epithelial cells, a poor prognosis in prostate cancer. We have shown that the only calcium channel expressed in the prostatic LNCaP cells is the alpha(1)H isoform and that induction of cell differentiation with cAMP leads to a concomitant increase in both T-type current and alpha(1)H mRNA. In spite of the presence of MR in these cells, aldosterone only modestly increased alpha(1)H mRNA levels. A functional role for these channels was suggested by the observation that low nickel concentrations prevent neuritic process outgrowth. In conclusion, it appears that T-type calcium channel expression vary in different patho-physiological conditions and that aldosterone, in several cell types, is able to modulate this expression.
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PMID:Aldosterone regulation of T-type calcium channels. 1294 26

Hypertension is an important determinant of heart failure. Ventricular systolic and/or diastolic dysfunction can eventuate in an activation of the renin-angiotensin-aldosterone system (RAAS). Circulating RAAS effector hormones lead to: the appearance of the congestive heart failure syndrome; and a systemic illness that features oxi/nitrosative stress in various tissues, including blood, together with circulating pro-inflammatory cytokines, anorexia and, ultimately, cachexia. In addition to its well-known endocrine properties, expressed in epithelial cells of classic target tissues, aldosterone (ALDO) has an emerging portfolio of actions in nonclassic target tissues, such as circulating lymphocytes and monocytes (or peripheral blood mononuclear cells [PBMC]). This neuroendocrine-immune interface is based on Na(+)-dependent, ALDO-induced iterations in PBMC cytosolic free [Mg(2+)](i) and [Ca(2+)](i). Ca(2+) loading contributes to an induction of oxi/nitrosative stress and activation of PBMC transcriptome. This immunostimulatory state begets a pro-inflammatory/fibrogenic vascular phenotype involving the heart and systemic organs and can be prevented by either ALDO receptor antagonism or antioxidant. The established efficacy of ALDO receptor antagonism as an integral component of the overall management of symptomatic heart failure may include its immunomodulatory properties. This brief review traces studies that led to and then identified the neuroendocrine-immune interface that accompanies aldosteronism.
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PMID:A neuroendocrine-immune interface. The immunostimulatory state of aldosteronism. 1468 3

Aldosterone exerts cardiovascular effects by influencing epithelial fluid and electrolyte excretion, and thus blood volume and pressure. Mineralocorticoid receptors (MR) are found in epithelial and non-epithelial tissues (vessel walls, heart, brain), with high affinity for aldosterone and physiological glucocorticoids cortisol and corticosterone. MR blockade by spironolactone or eplerenone favorably affects cardiovascular outcomes. In some situations (primary aldosteronism, experimental mineralocorticoid administration) activation of cardiovascular MR reflects aldosterone levels inappropriate for salt status. In others (heart failure, essential hypertension) aldosterone and Na(+) status are often normal pretreatment; cardiovascular MR may thus be activated by normal glucocorticoid levels after tissue damage and reactive oxygen species generation. Therefore, although unilateral adrenalectomy is preferred therapy for unilateral aldosterone-producing adenoma or hyperplasia, MR blockade may be useful in cardiovascular diseases where aldosterone levels are normal.
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PMID:Aldosterone as a cardiovascular risk factor. 1580 7

Aldosterone is the major mineralocorticoid hormone produced by the zona glomerulosa of the adrenal cortex. Aldosterone secretion is mainly regulated by the renin-angiotensin system, and to a minor extent by serum concentration of potassium, sodium, adrenocorticotropic hormone. and dopamine. This hormone, as well as other adrenal corticosteroids, exert many of its physiological actions through modulation of gene expression. It binds cytosolic receptors that translocate to the nucleus in a ligand-dependent manner and induces transcription of specific genes that encode for proteins involved in the cardiovascular homeostasis. Such proteins act regulating vascular tone, sympathetic nervous system activity, and hydroelectrolyte transport in epithelial tissues. Classical aldosterone target tissues are kidney, colon, sweat and salivary glands. Apart from the genomic effects, which imply a direct action on DNA, rapid non-genomic actions of aldosterone have been recently described in both epithelial and non-epithelial tissues and structures such as heart, vasculature, and kidney. At these sites aldosterone contributes to the development of cardiac fibrosis, myocardial hypertrophy, heart failure and arrhythmias; other deleterious effects exerted by aldosterone include vascular remodeling, endothelial dysfunction, perivascular inflammation, renal fibrosis, and progressive renal failure. Finally, recent evidence has focused on the possible implications of aldosterone excess on metabolic alterations, as described in patients with primary aldosteronism. On these premises lies the pathogenetic role of aldosterone in the development of cardiovascular diseases and the rationale for the use of mineralocorticoid receptor antagonists in the primary and secondary prevention of the complications related to these diseases.
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PMID:[Endocrinology of aldosterone]. 1594 95

Heart failure (HF) refractory to conventional therapy is a major and increasing public health and financial problem. Refractory HF is associated with hypervolaemia due to sodium and fluid retention, and azotaemia due to renal hypoperfusion. There is extreme renal salt and water retention and marked secondary hyperaldosteronism. In this state, the kidneys are relatively resistant to diuretic therapy, and the use of very high doses of oral or parenteral diuretics only worsens the renal hypoperfusion, making the patient more azotaemic. A logical treatment for this 'cardiorenal syndrome' is the use of dialysis, which is efficient in treating both the hypervolaemia and azotaemia of refractory HF. Peritoneal dialysis (PD), haemodialysis or continuous veno-venous haemofiltration can and have been used, but the simplest long-term treatment is PD. We present several case reports of the successful use of PD in refractory heart failure. In our opinion, chronic PD is a highly effective mode of treatment for refractory HF, and should be more widely used in this condition.
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PMID:The role of peritoneal dialysis in the treatment of refractory heart failure. 1602 32

Aldosterone is increasingly considered to have a fundamental role in the pathophysiology of cardiovascular disease. Primary aldosteronism is a much more common cause of secondary hypertension than once suspected, accounting for approximately 10% of cases. Screening for primary aldosteronism should be considered even in the presence of normokalaemia. The non-classical effects of aldosterone, some of which are transcription-independent, may be of similar or greater importance than its traditional effects on the kidney. Treatment of primary aldosteronism should be specific and aim to ameliorate all hormone-related effects of aldosterone, not just the most obvious manifestation of hypertension. Mineralocorticoid antagonism, shown to lead to significant additional survival advantage in heart failure, offers the best prospect for achieving therapeutic goals. For the increasing proportion of patients with primary aldosteronism suitable for long-term medical treatment, mineralocorticoid receptor blockade (better tolerated with eplerenone) should be considered the most appropriate choice of treatment, pending the development of better alternatives.
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PMID:The pharmacological treatment of primary aldosteronism. 1655 72

An emerging body of evidence suggests secondary hyperparathyroidism (SHPT) may be an important covariant of congestive heart failure (CHF), especially in African-Americans (AA) where hypovitaminosis D is prevalent given that melanin, a natural sunscreen, mandates prolonged exposure of skin to sunlight and where a housebound lifestyle imposed by symptomatic CHF limits outdoor activities and hence sunlight exposure. In addition to the role of hypovitaminosis D in contributing to SHPT is the increased urinary and fecal losses of macronutrients Ca(2+) and Mg(2+) associated with the aldosteronism of CHF and their heightened urinary losses with furosemide treatment of CHF. Thus, a precarious Ca(2+) balance seen with reduced serum 25(OH)D is further compromised when AA develop CHF with circulating RAAS activation and are then treated with a loop diuretic. SHPT accounts for a paradoxical Ca(2+) overloading of diverse tissues and the induction of oxidative stress at these sites which spills over to the systemic circulation. In addition to SHPT, hypozincemia and hyposelenemia have been found in AA with compensated and decompensated heart failure and where an insufficiency of these micronutrients may have its origins in inadequate dietary intake, altered rates of absorption or excretion and/or tissue redistribution, and treatment with an ACE inhibitor or AT(1) receptor antagonist. Zn and Se deficiencies, which compromise the activity of several endogenous antioxidant defenses, could prove contributory to the severity of heart failure and its progressive nature. These findings call into question the need for nutriceutical treatment of heart failure and which is complementary to today's pharmaceuticals, especially in AA.
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PMID:Macro- and micronutrients in African-Americans with heart failure. 1681 77

Hormonal regulation is not possible without the cardiovascular system, and thus the heart plays a special role not only in the action and synthesis, but also in the distribution of hormones. Severe endocrine disorders with cardiac involvement are often threatening for the patient. The impact of aberrant thyroid function, the sympathetic-adrenal symptoms of which predominantly affect the heart, is well known. Diabetes mellitus and the associated metabolic syndrome are major causes of cardiovascular disease and determine its morbidity and lethality rates. Acromegaly causes a complex cardiomyopathy that may result in cardiac failure refractive to conventional treatment. The excessive production of adrenal hormones in Cushing's syndrome, hyperaldosteronism and pheochromocytoma primarily harms the heart by causing severe hypertension. The same holds true for long-standing hyperparathyroidism. Recent prospective studies did not confirm the protective effect of hormone replacement therapy on cardiovascular disease.
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PMID:[Endocrine disorders and the heart]. 1733 54


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