Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary hyperparathyroidism (pHPT), caused by solitary parathyroid adenomas in 85% of cases and diffuse hyperplasia in most of the remaining cases, overproduces parathyroid hormone (PTH), which mobilizes calcium to the blood stream. Renal stones, osteoporosis and diffuse symptoms of hypercalcaemia, such as constipation, fatigue and weakness are well-known complications. However, in Western Europe and North America, patients with pHPT are nowadays usually discovered during an early, asymptomatic phase of the disease. It has been reported that patients suffering from symptomatic pHPT have increased mortality, mainly due to an overrepresentation of cardiovascular death. pHPT is reported to be associated with hypertension, disturbances in the renin-angiotensin-aldosterone system, and structural and functional alterations in the vascular wall. Recently, studies have indicated an association between pHPT and heart disease, and studies in vitro have produced a number of theoretical approaches. An increased prevalence of cardiac structural abnormalities such as left ventricular hypertrophy (LVH) and valvular and myocardial calcification has been observed. Associations have been found between PTH and LVH, and between LVH and serum calcium. LV systolic function does not seem to be affected in patients with pHPT, whereas any influence on LV diastolic performance needs further evaluation. The aim of this review is to clarify the connection between pHPT and cardiac disease.
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PMID:Primary hyperparathyroidism and heart disease--a review. 1547 92

1. If one was to design a hormone to protect the heart, it would have a number of features shown by the cardiac natriuretic peptides atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). These hormones are made in cardiomyocytes and are released into the circulation in response to atrial and ventricular stretch, respectively. Atrial natriuretic peptide and BNP can reduce the preload and after-load in normal and failing hearts. They reduce blood volume over the short term by sequestering plasma and over the longer term by promoting renal salt and water excretion and by antagonizing the renin-angiotensin-aldosterone system at many levels. Each of these actions affords indirect benefit to a volume- or pressure-threatened heart. 2. Recent studies have identified additional modes of action of the natriuretic peptides that may also confer cardioprotective benefits, especially in heart disease. The emerging findings are: (i) that ANP and BNP antagonize the cardiac hypertrophic action of angiotensin II and continue working under conditions where endothelial nitric oxide (NO) function is compromised, such as in the presence of high glucose in diabetes; (ii) they potentiate the bradycardia caused by inhibitory ('autoprotective') cardio-cardiac reflexes; and, furthermore, (iii) BNP can suppress cardiac sympathetic nerve activity in humans, including those with heart failure. Thus, it appears that natriuretic peptides can shift sympathovagal balance in a beneficial direction (away from the sympathetic). The vagal reflex and antihypertrophic actions of the peptides are mediated by particulate guanylyl cyclase (pGC) natriuretic peptide receptors. 3. The multiple synergistic actions of the natriuretic peptides make them and their pGC receptors attractive targets for therapy in heart disease. Encouragingly, exogenous natriuretic peptides remain effective even when endogenous peptide levels are raised, as is the case in heart failure. They also remain effective in disease states where other protective mechanisms, such as the NO system, have become ineffective, offering yet further encouragement for the therapeutic use of the natriuretic peptides.
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PMID:Cardioprotective functions of atrial natriuretic peptide and B-type natriuretic peptide: a brief review. 1556 95

A progressive chain of pathophysiological events links cardiovascular risk factors to clinical manifestations of disease and life-threatening cardiovascular events. This chain--the cardiovascular continuum--underlies cardiovascular disease and holds the key to its prevention and treatment. Progressive tissue damage can result in morbidity from congestive heart failure, end-stage heart disease, nephrotic proteinuria and dementia and, eventually, death from cardio- or cerebrovascular causes. The renin-angiotensin-aldosterone system (RAAS) is involved at all stages of the cardiovascular continuum, because the effector molecules of the RAAS, angiotensin II in particular, have direct pathobiological effects on a variety of tissues, including the endothelium, vascular smooth muscle and the renal mesangium. Clinical trials of angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors have demonstrated the essential validity of this hypothesis. Interruption of the RAAS has been shown to reduce cardiovascular morbidity and mortality in patients with left ventricular hypertrophy, heart failure and post-myocardial infarction, as well as renal disease in patients with type 2 diabetes. Key questions remain, however. What are the clinical effects of combination ARB and ACE inhibitor treatment? How will combinations of RAAS blockade with other agents, such as statins, affect the cardiovascular continuum? Answers to these questions will require well-planned, adequately powered clinical trials, such as the Programme of Research tO evaluate Telmisartan End-organ proteCTION (PROTECTION) and the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) programmes. However, it is already clear that RAAS blockade is an essential part of blocking progression along the cardiovascular continuum.
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PMID:The cardiovascular continuum and renin-angiotensin-aldosterone system blockade. 1582 52

Thus far, five molecules comprise the natriuretic peptide family (NPF): ANP, urodilatin, BNP, CNP and DNP. Precursor hormones for ANP, BNP and CNP are encoded by a different gene. Final peptides are ligands for A, B and C receptors, acting the latter as a clearance receptor besides neutral endopeptidase (EC 24.11). cGMP acts as a second messenger. Natriuretic peptides (NP) have well-known functions such as natriuretic, antihypertensive and reduction of plasma renin-aldosterone concentrations. An antiinflammatory ANP potential and a pro-apoptotic action in rats endothelial cells of different NP have been described. Unlike adults, NP show a different distribution during ontogeny and a different pattern of excretion under different stimuli. Noncompetitive immunoassays have become more suitable than competitive ones for routine measurement of NP with recent advances in speed of measurement. BNP and pro-BNP are emerging as useful tools in diagnosis, management and prognosis of heart disease. Preliminary data support a role of NP in the therapy of congestive heart failure. Finally, potential therapeutic compounds of NP in different pathologies are updated with an important focus on vasopeptidase inhibitors. These are capable of strengthening NP and inhibiting renin-angiotensin system at the same time, as potential useful molecules in cardiovascular therapy.
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PMID:Natriuretic peptide family: new aspects. 1585 96

A bidirectional relationship exists between depression and cardiovascular disease. Patients with major depression are more likely to develop cardiac events, and patients with myocardial infarction and heart failure are more likely to develop depression. A feature common to both clinical syndromes is activation of proinflammatory cytokines and stress hormones, including the hypothalamic-pituitary-adrenal axis and the renin-angiotensin-aldosterone system. In the present study we examined the hypothesis that exposure to chronic mild stress (CMS), an experimental model of depression that induces anhedonia in rats, is sufficient to activate the production of proinflammatory cytokines and stress hormones that are detrimental to the heart and vascular system. Four weeks of exposure of male, Sprague-Dawley rats to mild unpredictable environmental stressors resulted in anhedonia which was operationally defined as a reduction in sucrose intake without a concomitant effect on water intake. Humoral assays indicated increased plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), plasma renin activity, aldosterone, and corticosterone in the CMS exposed rats. Tissue TNF-alpha and IL-1beta were increased in the hypothalamus, and TNF-alpha was increased in the pituitary gland. These humoral responses to CMS, associated with anhedonia as an index of depression in the rat, are likely to be associated with neurohumoral mechanisms that may contribute to adverse cardiac events. The findings provide a basis for examining more directly the interactions among the central, endocrine, and immune systems in depression associated with heart disease.
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PMID:Neuroendocrine and cytokine profile of chronic mild stress-induced anhedonia. 1588 45

The understanding of cardiac failure pathophysiology in children has advanced greatly in recent years. Whilst cardiac failure secondary to left ventricular dysfunction with viral or metabolic cardiomyopathy is comparable in pathophysiological terms with adults, other aetiological mechanisms are also implicated, linked both to anatomical anomalies in congenital cardiopathy and their surgical repair. The role of the neuroendocrine system with adrenergic activation of the renin-angiotensin system, secretion of natriuretic peptides and the inflammatory system, before and during surgical repair procedures, have been proven both experimentally and clinically. Understanding these pathophysiological mechanisms opens new therapeutic perspectives for improving the management of children with congenital cardiopathy in cardiac failure and reducing postoperative mortality and morbidity.
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PMID:[Cardiac failure in children]. 1596 9

Enhanced understanding of the mechanisms underlying atrial fibrillation (AF) and advent of catheter-based therapy for AF has altered the approach to patients with this most common arrhythmia. However, despite the success of aggressive procedural techniques, pharmacologic therapy remains the first-line and mainstay approach in the treatment of AF. This review of new antiarrhythmic drug (AAD) therapy for AF provides an in-depth overview of recently available classic and new investigational drugs being considered for AF treatment. Currently available AADs are associated with less than satisfactory efficacy in preventing AF and a significant side effect profile, including ventricular proarrhythmia. Recent investigations have focused on development of new AADs that, hopefully, will be more effective and safer even in patients with structural heart disease. These new AADs include selective multi-ion channel and atrial specific blockers and agents that target the underlying etiologies and substrate alterations that lead to AF. Included among the latter new category are agents that suppress activation of the renin-angiotensin-aldosterone system or inflammation, which represent novel targets for drug therapy for AF. Finally, new selective A1 adenosine receptor agonists may offer the possibility of more specific and successful ventricular rate control during AF. There is considerable hope and interest that improved understanding of AF mechanisms ultimately will result in more effective and less dangerous pharmacologic therapy becoming available in the future.
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PMID:New antiarrhythmic drugs for prevention of atrial fibrillation. 1627 45

Although blood pressure and heart rate effects have been reported for adrenomedullin 2 (AM-2), a new member of the calcitonin gene-related peptide superfamily, little information is available regarding other biological actions of systemically administered AM-2. Accordingly, we report for the first time the integrated hemodynamic, hormonal, and renal actions of the AM-2 in normal conscious sheep. AM-2 induced significant reductions in mean arterial pressure (P < 0.001). This was associated with dose-dependent rises in heart rate (P < 0.001) and cardiac output (P < 0.001) and dose-dependent falls in calculated total peripheral resistance (P < 0.001). Right atrial pressure was increased post infusion (P = 0.026), whereas hematocrit fell post infusion (P = 0.001). AM-2 also induced significant hormonal changes, particularly in the renin-angiotensin-aldosterone system where plasma renin activity was significantly activated (P < 0.001) associated with a dose-dependent rise in plasma aldosterone (P < 0.001). Plasma cAMP also rose in response to AM-2 (P < 0.001), as did circulating levels of the natriuretic peptides, particularly post infusion. In conclusion, iv infusions of AM-2 administered to normal conscious sheep induced significant hemodynamic actions including reduced mean arterial pressure and calculated total peripheral resistance and increased heart rate and cardiac output. Concurrently, AM-2 activated plasma cAMP, plasma renin activity, aldosterone, and the natriuretic peptides. With the exception of actions on aldosterone, these actions are similar to those previously reported for AM. Thus, AM-2 may be another important regulator of volume and pressure homeostasis and may play a role in the pathophysiology of heart disease.
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PMID:Hemodynamic, hormonal, and renal actions of adrenomedullin-2 in normal conscious sheep. 1641 Feb 98

The incidence of diabetes is increasing at an alarming rate to the point where it is becoming an epidemic. An ageing population, sedentary lifestyle and an unhealthy diet are considered to have contributed toward this. What we must now consider is not only the burden of the disease but the complications that arise from diabetes, in particular kidney and heart disease. Foremost, more than half of the diabetic population will die from cardiovascular-related causes. Whilst diabetes is most often associated with hypertension, dyslipidaemia and obesity, these factors do not fully account for the increased burden of cardiovascular disease in people with diabetes. This strengthens the need for comprehensive studies investigating the underlying mechanisms mediating diabetic cardiovascular disease, and more specifically, diabetes-associated atherosclerosis. In addition to the recognised metabolic abnormalities associated with diabetes, upregulation of putative pathological pathways such as advanced glycation endproducts, renin-angiotensin system, oxidative stress and increased expression of growth factors and cytokines have been observed in the setting of diabetes. All of these have been shown to play a causal role in atherosclerotic plaque formation and thus may explain the increased risk of macrovascular complications in those patients with diabetes. In this review the effect of inhibiting the renin-angiotensin system with angiotensin converting enzyme inhibition and a comparison to angiotensin II receptor antagonism is discussed, with the results of clinical trails reflecting the more recently discovered, non-haemodynamic, proatherogenic actions of angiotensin II. The need for experimental models of diabetes-associated atherosclerosis will be covered, with particular emphasis given to the streptozotocin-diabetic apolipoprotein E knockout mouse. Finally, growth factors, including vascular endothelial growth factor and platelet-derived growth factor are discussed in detail.
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PMID:Preventing atherosclerosis with angiotensin-converting enzyme inhibitors: emphasis on diabetic atherosclerosis. 1650 70

The renin-angiotensin-aldosterone system (RAAS) has been implicated in the pathophysiology of salt-induced hypertension. Angiotensin converting enzyme inhibitors, angiotensin II-type 1 receptor blockers, and aldosterone receptor blockers are used to treat hypertension and congestive heart disease. In addition to their blood pressure lowering effects, they appear to protect against myocardial, renal, and vascular damage. In various models of hypertension, generation of reactive oxygen species is increased in the vasculature and that treatment with antioxidants or superoxide dismutase mimetics (e.g., tempol) improves vascular function and structure and reduces blood pressure. The purpose of this study was to examine the effects of enalapril, an angiotensin II converting enzyme inhibitor; eplerenone, a selective aldosterone receptor antagonist; and tempol, a superoxide dismutase mimetic, on salt-induced hypertension in Dahl Salt-Sensitive rats. The rats were placed on a high salt (HS; 8%) diet for 3 weeks prior to switching to a normal salt (0.3%) diet for an additional 3 weeks. While on the normal salt (NS) diet, rats were treated with enalapril (30 mg/kg/day in the drinking water), eplerenone (100 mg/kg/day by gavage), tempol (1 mM/day in the drinking water), eplerenone + enalapril, eplerenone + enalapril + tempol, or without drug treatment (control). After 3 weeks on HS diet, systolic blood pressure rose from 127 +/- 7 to 206 +/- 11 mm Hg and remained elevated when switched to NS diet. Subsequently, treatment with eplerenone alone or in combination with enalapril and tempol produced a stepwise reduction in systolic blood pressure reaching -80 mm Hg; however, enalapril and tempol alone produced more modest pressure reduction (approximately -35 mmHg). Plasma levels of prostacyclin and nitric oxide were elevated in rats treated with enalapril and eplerenone alone or in combination. Enalapril and eplerenone alone and in combination reduced heart and kidney levels of angiotensin II and aldosterone when compared with control. Renal and heart levels of reduced glutathione were diminished by eplerenone alone; however, enalapril tended to attenuate the effect of eplerenone on reduced glutathione levels in the heart. The findings from this study suggest that eplerenone reduces salt-induced hypertension by increasing endothelium-derived relaxing factors, inhibiting RAAS components and oxidative stress. (353words).
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PMID:Effects of enalapril, tempol, and eplerenone on salt-induced hypertension in dahl salt-sensitive rats. 1654 38


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