Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erectile dysfunction (ED) is a common problem in male patients with heart failure (HF). However, no study was found that estimates the prevalence of ED by US ethnic groups with HF. We conducted an observational, cross-sectional study of patients enrolled in a HF disease management program in two sites Louisiana (N=329; 178 white, 99 black) and Florida (N=52; Hispanic). All male patients with an ejection fraction <or=40% were included. The Sexual Health Inventory for Men was used to estimate the prevalence of ED. Overall prevalence of ED was 89% and ED severity did not vary by race/ethnic group. Race/ethnic group differences were found for age, New York Heart Association functional classification, and blood pressure. Hispanic patients had the lowest unadjusted and adjusted prevalence rate of ED (81, 85%) compared to Black (90, 95%) and White (91, 92%) patients. There is a high prevalence of ED in Hispanic, Black and White ethnic groups with HF.
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PMID:The prevalence of erectile dysfunction in heart failure patients by race and ethnicity. 1870 19

Phosphodiesterases (PDEs) are enzymes that degrade cellular cAMP and cGMP and are thus essential for regulating the cyclic nucleotides. At least 11 families of PDEs have been identified, each with a distinctive structure, activity, expression, and tissue distribution. The PDE type-3, -4, and -5 (PDE3, PDE4, PDE5) are localized to specific regions of the cardiomyocyte, such as the sarcoplasmic reticulum and Z-disc, where they are likely to influence cAMP/cGMP signaling to the end effectors of contractility. Several PDE inhibitors exhibit remarkable hemodynamic and inotropic properties that may be valuable to clinical practice. In particular, PDE3 inhibitors have potent cardiotonic effects that can be used for short-term inotropic support, especially in situations where adrenergic stimulation is insufficient. Most relevant to this review, PDE inhibitors have also been found to have cytoprotective effects in the heart. For example, PDE3 inhibitors have been shown to be cardioprotective when given before ischemic attack, whereas PDE5 inhibitors, which include three widely used erectile dysfunction drugs (sildenafil, vardenafil and tadalafil), can induce remarkable cardioprotection when administered either prior to ischemia or upon reperfusion. This article provides an overview of the current laboratory and clinical evidence, as well as the cellular mechanisms by which the inhibitors of PDE3, PDE4 and PDE5 exert their beneficial effects on normal and ischemic hearts. It seems that PDE inhibitors hold great promise as clinically applicable agents that can improve cardiac performance and cell survival under critical situations, such as ischemic heart attack, cardiopulmonary bypass surgery, and heart failure.
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PMID:Pivotal effects of phosphodiesterase inhibitors on myocyte contractility and viability in normal and ischemic hearts. 1906 Sep 15

The nitric oxide (NO) signalling pathway is altered in cardiovascular diseases, including systemic and pulmonary hypertension, stroke, and atherosclerosis. The vasodilatory properties of NO have been exploited for over a century in cardiovascular disease, but NO donor drugs and inhaled NO are associated with significant shortcomings, including resistance to NO in some disease states, the development of tolerance during long-term treatment, and non-specific effects such as post-translational modification of proteins. The development of pharmacological agents capable of directly stimulating the NO receptor, soluble guanylate cyclase (sGC), is therefore highly desirable. The benzylindazole compound YC-1 was the first sGC stimulator to be identified; this compound formed a lead structure for the development of optimized sGC stimulators with improved potency and specificity for sGC, including CFM-1571, BAY 41-2272, BAY 41-8543, and BAY 63-2521. In contrast to the NO- and haem-independent sGC activators such as BAY 58-2667, these compounds stimulate sGC activity independent of NO and also act in synergy with NO to produce anti-aggregatory, anti-proliferative, and vasodilatory effects. Recently, aryl-acrylamide compounds were identified independent of YC-1 as sGC stimulators; although structurally dissimilar to YC-1, they have a similar mode of action and promote smooth muscle relaxation. Pharmacological stimulators of sGC may be beneficial in the treatment of a range of diseases, including systemic and pulmonary hypertension, heart failure, atherosclerosis, erectile dysfunction, and renal fibrosis. An sGC stimulator, BAY 63-2521, is currently in clinical development as an oral therapy for patients with pulmonary hypertension. It has demonstrated efficacy in a proof-of-concept study, reducing pulmonary vascular resistance and increasing cardiac output from baseline. A full, phase 2 trial of BAY 63-2521 in pulmonary hypertension is underway.
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PMID:NO-independent, haem-dependent soluble guanylate cyclase stimulators. 1908 34

Cyclic guanosine 3', 5'-monophosphate (cGMP) plays an integral role in the control of vascular function. Generated from guanylate cyclases in response to the endogenous ligands, nitric oxide (NO) and natriuretic peptides (NPs), cGMP influences a number of vascular cell types and regulates vasomotor tone, endothelial permeability, cell growth and differentiation, as well as platelet and blood cell interactions. Reciprocal regulation of the NO-cGMP and NP-cGMP pathways is evident in the vasculature such that one cGMP generating system may compensate for the dysfunction of the other. Indeed, aberrant cGMP production and/or signalling accompanies many vascular disorders such as hypertension, atherosclerosis, coronary artery disease and diabetic complications. This chapter highlights the main vascular functions of cGMP, its role in disease and the resulting current and potential therapeutic applications. With respect to pulmonary hypertension, heart failure and erectile dysfunction, as well as cGMP signal transduction, the reader is specifically referred to other dedicated chapters.
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PMID:cGMP in the vasculature. 1908 40

Aldosterone is a steroid hormone that controls blood pressure by binding to the mineralocorticoid receptor (MR), a ligand-activated transcription factor, and regulating genes that play a role in salt and water homeostasis in the kidney. Dysregulation of the mineralocorticoid system reveals its crucial role in various human diseases including hypertension, atherosclerosis, cardiac failure, mineralocorticoid resistance, and disorders of the nervous system. Recently, experimental animal models of mineralocorticoid/salt-induced hypertension and atherosclerosis have revealed an epithelial, pro-inflammatory role for MR activation. Extensive investigation has begun to elucidate the mechanisms underlying the vascular effects of MR activation which involve its direct role in cardiomyocytes, vascular smooth muscle cells, and endothelial cells. More specifically, in patients with cardiovascular risk factors and disease, including diabetes, hypertension, and/or congestive heart failure, an excess of MR activation has been shown to have a negative impact on endothelial function hence disrupting the physiological balance between vasoconstriction and vasodilation. Such a mechanism may play a role in the pathogenesis of erectile dysfunction (ED), a condition that occurs frequently in patients with increased cardiovascular risk and involves endothelial dysregulation of vascular relaxation. The aim of this review is to summarize the latest concepts in MR signaling, with particular attention to the endothelium, and to discuss the potential benefits of tissue-selective MR blockade in treating subsets of ED patients, such as those with congestive heart failure and hypertension, in which the MR system may be over activated.
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PMID:The mineralocorticoid receptor in endothelial physiology and disease: novel concepts in the understanding of erectile dysfunction. 1912 27

Phosphodiesterase 5 (PDE5) selectively hydrolyzes cyclic guanosine monophosphate. Inhibitors of PDE5 were originally developed to treat angina pectoris, and currently have multiple therapeutic indications, including erectile dysfunction and pulmonary hypertension. Several lines of research have provided evidence to support various potential PDE5-dependent cellular mechanisms in the myocardium that are involved in the pathophysiology of heart failure and cardiac dysfunction. In this Review we provide a mechanistic overview of the pharmacological inhibition of PDE5 in the context of heart failure, and evaluate the evidence supporting the use of novel PDE5 inhibitors in the treatment of this condition.
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PMID:Phosphodiesterase 5 inhibition in heart failure: mechanisms and clinical implications. 1937 97

The phosphodiesterase type 5 (PDE-5) inhibitors are effective in treating erectile dysfunction (ED). ED and heart failure (HF) share similar risk factors, and commonly present together. This association has led to questions ranging from the safety and efficacy of PDE-5 inhibitors in HF patients to a possible role for this class of medication to treat HF patients with or without ED. In addition to endothelial dysfunction, there are causes of ED specific to patients with HF including low exercise tolerance, depression and HF medications. Before treating HF patients with PDE-5 inhibitors, patients should be assessed for their risk of a cardiac event during sexual activity. PDE-5 inhibitors are safe and effective in treating ED in HF patients. An improvement in erectile function by PDE-5 inhibitors was associated with an improvement in quality of life and reduction in depression. Several studies demonstrated the effect of PDE-5 inhibitors on HF per se. PDE-5 inhibitors improved endothelial dysfunction, increased exercise tolerance, decreased pulmonary vascular resistance and pulmonary artery pressure, and increased cardiac index. Several mechanisms whereby PDE-5 inhibitors improve HF have been proposed. PDE-5 inhibitors already have a role in treating primary pulmonary hypertension; however additional studies are needed to determine if they will become a standard therapy for HF patients.
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PMID:Erectile dysfunction and heart failure: the role of phosphodiesterase type 5 inhibitors. 1938 54

Phosphodiesterase type-5 (PDE5) inhibitors are widely used as first-line therapy for erectile dysfunction (ED). Their efficacy and safety combined with an increasing understanding of cyclic guanosine monophosphate (cGMP)-regulated mechanisms, have triggered a number of attempts to determine their effects and potential benefits in non-urological conditions. In recent years, extensive and diverse preclinical and clinical evidence has been made available. PDE5 inhibition has shown collateral benefits for a multitude of risk factors or diseases associated with, or accompanying ED. To date, PDE5 inhibition has been shown to be effective for the treatment of idiopathic pulmonary arterial hypertension and both sildenafil and tadalafil are approved for this indication. However, PDE5 inhibitors appear to have the potential of further expanding their indications. Importantly, accumulating data show that the therapeutic potential extends to the cardiovascular, gastrointestinal, cutaneous and nervous system and that these agents may be beneficial in a multitude of conditions such as Raynaud's phenomenon, heart failure, essential hypertension and stroke. PDE5 inhibitors are a conceptually attractive therapeutic class of agents with pleiotropic effects. The present review discusses recent findings regarding the effects of PDE5 inhibitors on non-urological conditions and highlights current and future clinical applications beyond ED.
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PMID:PDE5 inhibitors in non-urological conditions. 1986 Jun 98

PDE-5 inhibitors were originally studied in cardiovascular indications but were later developed and approved for on-demand treatment of erectile dysfunction (ED). A few years ago sildenafil was approved for the treatment of pulmonary hypertension, thus renewing interest in cardiovascular applications, and tadalafil became available in once-daily formulations for erectile dysfunction management. Given the wide distribution of phosphodiesterase-5 throughout the body and its involvement in multiple functions, what can one expect in the future? To answer this we reviewed studies involving PDE-5 inhibitors that were published within the past three years and searched the US National Institutes of Health clinical trial registry for ongoing ones. PDE-5 inhibitors are being actively investigated in many disease states, with interest focusing mainly on urology and cardiovascular medicine. In urology erectile dysfunction is the primary target, followed by BPH-related lower urinary tract symptoms. As far as cardiovascular medicine is concerned, treatment of heart failure is the indication where PDE-5 inhibitors seem to be closer to clinical application but preclinical data also support a role in cardiac preconditioning.
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PMID:Phosphodiesterase-5 inhibitors: future perspectives. 1986 Jun 99

The prevalence of erectile dysfunction (ED) increases with age. ED has organic aetiologies and is associated with other clinical comorbidities. Men with ED are more likely to have: cardiac disease, diabetes, hypercholesterolaemia, angina, hypertension, prostate disease and depression. Similarly, men with these conditions are more likely to have ED. It is believed that vasculogenic ED shares a common aetiology with coronary artery disease, including hyperlipidaemia, diabetes and hypertension. Taking a careful history of onset, duration and associated symptoms may reveal possible causes of ED. Past medical history, disease control, trauma and medication use can provide vital information. ED patients with a sedentary lifestyle should be encouraged to exercise. In obese men, weight loss of 10% or more can improve IIEF score. Regular exercise, healthy diet, smoking cessation, limiting alcohol intake and avoiding recreational drugs can reduce the risk of, or improve, ED. It is important to differentiate between patients suffering from nocturnal frequency, enuresis or nocturnal polyuria as the causes and treatments for each of these conditions are different. Reducing fluid intake after 6 pm and avoiding alcohol and/or caffeine at night may reduce nocturnal voiding. Anticholinergics can decrease bladder overactivity. An improvement in nocturia and nocturia bother score have been shown after administration of oral melatonin. Nocturnal enuresis can often be the only symptom of high-pressure chronic retention which is prevalent in older men. It is important to recognise this condition as treatment can prevent further renal impairment. In nocturnal polyuria the urine output at night is more than a third of the total daily urine output. If conservative measures are not successful, in the absence of heart failure, a low-dose diuretic in the afternoon can help the kidneys get rid of the fluid before bedtime.
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PMID:Diagnosing urological disorders in ageing men. 2030 27


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