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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although results of randomized trials have demonstrated the beneficial effects of ACE-inhibitors, mortality and morbidity remain high in patients with heart failure and myocardial infarction. In fact, there are data suggesting that aldosterone production may occur despite ACE-inhibitor treatment. There is recent evidence that aldosterone exerts a pro-fibrotic effect, via the mineralocorticoid receptors in cardiovascular tissues resulting in partial aldosterone production during ACE-inhibitor treatment. Mineralocorticoids have also been identified within the cardiovascular system and they may determine increased collagen synthesis which within fibroblasts is largely controlled by locally generated aldosterone. Cardiovascular tissue also expresses genes which are responsible for the late stages of aldosterone and corticosterone formation. Cardiac and vascular tissues elaborate the aforementioned steroids, with the result that aldosterone is more concentrated in the cardiovascular tissue rather than in the circulation. It is probable that locally, while not contributing to the coronary circulation, aldosterone plays an autocrine and/or paracrine role within the tissue of origin. Such roles may relate to local modulation of vessel tonicity and structure, with consequent effects on blood pressure, and repair of damaged tissue through a possible up-regulation of collagen deposition. The ability of the cardiovascular system to elaborate aldosterone opens a vast new area of study since it is becoming increasingly apparent that this local production of mineralocorticoids results in high levels of steroids within the cells of origin and those in the immediate vicinity. The recent RALES trial has shown a significant reduction in mortality, non-fatal hospitalization and sudden death. The fact that patients were on ACE-inhibitors, and accordingly circulating aldosterone levels were presumably reduced, presents the intriguing possibility that spironolactone may block the autocrine and paracrine effects of locally generated aldosterone. This trial has contributed to better understand the pathophysiology of heart failure and its therapeutic strategies. Further studies are required to address this treatment in patients with other heart diseases (hypertension, post-myocardial infarction) and in lower heart failure classes.
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PMID:Mineralocorticoids and cardiovascular diseases. Status of knowledge from experimental and clinical studies. 1113 Aug 38

Cardiac extracellular matrix undergoes extensive and continuous turnover involved in the lesion-reparation process, such as in cardiac remodeling, in hypertensive cardiac hypertrophy, in dilated cardiomyopathy, after myocardial infarction in the transition to heart failure, and during the progression of left ventricular dysfunction. Cardiac fibrosis is a major determinant of diastolic dysfunction and pumping capacity, and it may provide the structural substrate for arrhythmogenicity, thus potentially contributing the to progression of heart failure and sudden death. Aldosterone was shown to promote cardiac fibrosis in various experimental models. It was demonstrated that spironolactone may oppose the effect of aldosterone in promoting cardiac fibrosis. Measurement of cardiac collagen turnover by use of serological markers is a useful tool for monitoring cardiac tissue repair and fibrosis in experimental models or clinical conditions. We found that high serum levels of a marker of collagen turnover (procollagen type III N-terminal peptide ) in patients with chronic heart failure receiving conventional therapy, including ACE inhibitors, was associated with high mortality and hospitalization rates. In RALES (Randomized Aldactone Evaluation Study), in patients randomized to placebo, markers continued to increase or remained unchanged after 6-month follow-up. On the contrary, adding spironolactone 25 mg daily significantly decreased the levels of these serum markers during the same period. Most importantly, the spironolactone-related morbidity and mortality benefit was most predominant in subgroups with highest baseline levels of serum markers. These results suggest that limitation of the aldosterone-related excessive extracellular matrix turnover may be one of the various extrarenal mechanisms contributing to the beneficial effect of spironolactone in patients with chronic heart failure.
Hypertension 2001 Nov
PMID:Treatment of congestive heart failure: interfering the aldosterone-cardiac extracellular matrix relationship. 1171 28

To determine whether clinical parameters alone can differentiate normal versus decreased systolic left ventricular function in patients with heart failure. Detailed clinical data were collected prospectively from 225 consecutive patients who were hospitalized with heart failure. Findings in patients with normal (ejection fraction > or =45%) or decreased (ejection fraction <45%) left ventricular function were compared. Systolic function was normal in 104 patients (46%) and decreased in 121 patients (54%). Patients with normal function were older (mean [+/- SD] age, 59 +/- 13 years vs. 54 +/- 13 years, P = 0.007) and more likely to be female (56% vs. 35%, P = 0.001), obese (body mass index > or =30 kg/m(2), 62% vs. 48%, P = 0.04), have marked systolic (> or =160 mm Hg, 50% vs. 27%, P <0.001) and diastolic (> or =110 mm Hg, 25% vs. 13%, P = 0.02) hypertension, and use calcium antagonists (34% vs. 14%, P = 0.001). Patients with decreased function were more likely to use alcohol (37% vs. 20%, P = 0.007), angiotensin-converting enzyme (ACE) inhibitors (85% vs. 62%, P <0.001), and digoxin (57% vs. 27%, P <0.001); and more likely to have tachycardia (51% vs. 32%, P = 0.004), rales (89% vs. 80%, P = 0.05), electrocardiographic left ventricular hypertrophy (42% vs. 22%, P = 0.002), left atrial abnormality (52% vs. 22%, P <0.001), or flow cephalization on chest radiograph (91% vs. 79%, P = 0.02). Only sex, tachycardia, and use of digoxin and ACE inhibitors were associated with ventricular function in multivariable analysis. However, the sensitivity, specificity, and predictive values for all clinical variables were low. Differences in clinical parameters in heart failure patients with decreased versus normal systolic function cannot predict systolic function in these patients, supporting recommendations that heart failure patients should undergo specialized testing to measure ventricular function.
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PMID:Utility of history, physical examination, electrocardiogram, and chest radiograph for differentiating normal from decreased systolic function in patients with heart failure. 1251 72

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

The activation of the different neurohumoral system plays an important role in the different mechanisms of the development and progression of arterial hypertension and chronic heart failure. The renin-angiotensin II-aldosterone system is one of the key players in this process. With the use of ACE-inhibitors in the treatment of hypertension and heart failure, less attention has been paid to aldosterone. Aldosterone has been only considered as a humoral factor playing a role in salt and water homeostasis and as a consequence controlling arterial blood pressure. There is now evidence of vascular synthesis of aldosterone besides the secretion at the adrenal cortex as well that aldosterone is involved in the development of left ventricular hypertrophy in arterial hypertension, decreased arterial elasticity of the large arteries in chronic heart failure and is inversely correlated with venous capacitance in chronic heart failure. Moreover aldosterone plays a role in the disturbances of the vascular matrix, endothelial dysfunction as well as baroreflex dysfunction. This work has contributed indirectly in the unraveling of the mechanisms which could be partly explained the results of the RALES-trial. The new research project will be focused on the study of the cross-talk between the autonomic nervous system and aldosterone in normotension, arterial hypertension and heart failure.
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PMID:[Aldosterone and cardiovascular diseases, more than water and salt retention]. 1223 44

Flash pulmonary edema is a paroxismal pulmonary edema associated to a hypertensive crisis, that subsides in hours with the usual therapeutic measures. It occurs in patients with renal artery stenosis. We report two male patients aged 71 and 74 years old, presenting with acute dyspnea and high blood pressure. Diffuse rales were auscultated and arterial blood pressure was high in both. Dyspnea subsided in few hours with diuretics and oxygen. In both, a critical renal arterial stenosis was found and an angioplasty with stent placement was performed. After 5 and 6 months of follow up, the patients remain asymptomatic.
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PMID:[Flash pulmonary edema: when the kidney causes decompensation of the heart]. 1243 52

Although the role of the systemic renin-angiotensin-aldosterone system in the pathophysiology of heart failure is well-known for years, the impact of a local cardiac aldosterone system has been recognized recently. Aldosterone promotes cardiac hypertrophy and fibrosis in hypertension and heart failure and is involved in left ventricular remodeling after myocardial infarction. Plasma aldosterone levels in patients with heart failure are an indicator of a worse prognosis. Although ACE inhibitor therapy in these patients reduces plasma aldosterone levels, this effect is only transitory, a phenomenon referred to as "aldosterone escape". Even maximally recommended doses of ACE inhibitors do not completely prevent ACE-mediated formation of angiotensin II in chronic heart failure, and those patients with increased aldosterone levels during ACE inhibition have impaired exercise capacity. The RALES study has demonstrated convincingly that in patients with heart failure, addition of the mineralocorticoid receptor antagonist spironolactone (25 mg/d) to ACE inhibition markedly reduces mortality and prevents worsening heart failure. While reduction of excessive extracellular matrix turnover leading to decreased fibrosis appears to be the most important effect of spironolactone in heart failure, other mechanisms such as regression of hypertrophy, improvement of endothelial function, enhanced renal sodium excretion and antiarrhythmic actions may contribute. In RALES, low-dose spironolactone did not confer a substantial risk of hyperkalemia, however, with broader use of spironolactone in heart failure, cases of hyperkalemia associated with the use of this drug increase. Close control of serum potassium and creatinine and estimation of creatinine clearance are mandatory, especially in the presence of additional factors impairing renal function. The new and more selective aldosterone antagonist eplerenone which is devoid of some side effects of spironolactone, has been shown to be effective in hypertension and holds great promise as future therapeutic agent in patients with heart failure.
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PMID:Aldosterone antagonism in addition to angiotensin-converting enzyme inhibitors in heart failure. 1278 71

In most countries the last two decades have seen a very substantial rise in the prevalence of heart failure, and in a majority of patients hypertension is both an antecedent condition and a contributing cause. Heart failure is also a major cause of hospital admissions; its amelioration and, as far as possible, prevention is therefore important in terms not only of morbidity and premature mortality for the individual patient, but also containment of healthcare costs. Over the past 5 years, mineralocorticoid receptor (MR) antagonists have been used in two major outcome trials (the Randomized Aldactone Evaluation Study [RALES] with spironolactone, and the Eplerenone Post-AMI Heart Failure Efficacy and Survival Study [EPHESUS]), in severe (New York Heart Association class III) and post-myocardial infarct heart failure, respectively. Experimental studies have largely focused, however, on various animal models of hypertension; on the basis of a portfolio of clinical studies on the efficacy of eplerenone, administered either alone and in combination as an antihypertensive agent, the novel MR antagonist was approved by the FDA for the treatment of hypertension, though it has yet to be launched. In this review, the two major outcome studies (RALES, EPHESUS) are discussed in the context of the new biology of aldosterone action. The relevance to heart failure of current experimental studies, largely on vascular protection, will also be discussed.
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PMID:The role of mineralocorticoid receptor antagonists in the treatment of cardiac failure. 1464 Sep 40

Recent studies suggest that a dysregulation of the aldosterone system is involved in the pathophysiology of different cardiovascular diseases, including myocardial failure and several cases of essential hypertension. In both rat models and in humans, aldosterone action has been shown to induce heart remodeling and interstitial and perivascular fibrosis of the myocardium. For these reasons, a rationale for the use of aldosterone antagonists (ARAs) of the spirolactone family, which have been available for decades in the treatment of aldosterone excess syndromes, has now emerged. Moreover, the recent validation of their use, in combination with the current therapy, for the treatment of these cardiovascular diseases by trials like the RALES Study has further strenghtened this approach. The development of compounds, like eplerenone, with a greater selectivity for mineralocorticoid receptors, seems promising also in terms of reduction of endocrine side effects. The addition of aldosterone antagonists to the conventional therapy of myocardial failure and of selected cases of hypertension thus appears beneficial, resulting in an improved survival rate and a reduced incidence of cardiac complications. This review article, after a brief recall of the physiology of the aldosterone system, addresses the emerging role of aldosterone in cardiovascular diseases, considers the pharmacology of ARAs and the novel therapeutical applications of these compounds in hypertension and heart failure.
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PMID:Aldosterone receptor antagonists: biology and novel therapeutical applications. 1466 38

Aldosterone is one the representative cardiovascular hormones involved in the blood pressure and body-fluid homeostasis. Elevation of aldosterone leads to systemic hypertension through its action on the mineralocorticoid receptor (MR) in the kidney. More recent studies demonstrated that aldosterone may produce target organ damage through its direct actions on the non-epithelial MR of the heart in addition to its systemic effects. Clinical experience in primary aldosteronism supports the concept that aldosterone is a risk factor of cardiovascular complications, since concentric type of cardiac hypertrophy is most common in primary aldosteronism among various types of endocrine hypertension. Clinical mega-trial in congestive heart failure (RALES study, EPHESUS study) demonstrated blocking angiotensin II action is not sufficient for cardioprotection unless aldosterone action is equally blocked. An important phenomenon related to this issue is the aldosterone breakthrough which implies a reelevation of plasma aldosterone during chronic administration of ACE inhibitors and Angiotensin receptor antagonists. Normal level of aldosterone could still be a risk factor. Combination of ACE inhibitor or ARB with aldosterone antagonist could result in a better cardioprotection in cardiovascular diseases. Although spironolactone has been the only one aldosterone antagonist, a new antagonist eplerenone has been developed. Eplerenone is specific to MR and is practically devoid of the major side effect gynecomastia of spironolactone. Another topic of aldosterone is its very quick cardiovascular effect presumably via a non-genomic action. All these recent findings support that this adrenocortical steroid hormone is as important as angiotensin II. Determining aldosterone levels is therefore much morel important than before in the diagnosis and treatment of cardiovascular diseases.
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PMID:[Aldosterone]. 1547 26


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