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

The prognosis of patients with pulmonary arterial hypertension (PAH) is poor. Available therapies (Ca(++)-channel blockers, epoprostenol, bosentan) have limited efficacy or are expensive and associated with significant complications. PAH is characterized by vasoconstriction, thrombosis in-situ and vascular remodeling. Endothelial-derived nitric oxide (NO) activity is decreased, promoting vasoconstriction and thrombosis. Voltage-gated K+ channels (Kv) are downregulated, causing depolarization, Ca(++)-overload and PA smooth muscle cell (PASMC) contraction and proliferation. Augmenting the NO and Kv pathways should cause pulmonary vasodilatation and regression of PA remodeling. Several inexpensive oral treatments may be able to enhance the NO axis and/or K+ channel expression/function and selectively decrease pulmonary vascular resistance (PVR). Oral L-Arginine, NOS' substrate, improves NO synthesis and functional capacity in humans with PAH. Most of NO's effects are mediated by cyclic guanosine-monophosphate (c-GMP). cGMP causes vasodilatation by activating K+ channels and lowering cytosolic Ca++. Sildenafil elevates c-GMP levels by inhibiting type-5 phosphodiesterase, thereby opening BK(Ca). channels and relaxing PAs. In PAH, sildenafil (50 mg-po) is as effective and selective a pulmonary vasodilator as inhaled NO. These benefits persist after months of therapy leading to improved functional capacity. 3) Oral Dichloroacetate (DCA), a metabolic modulator, increases expression/function of Kv2.1 channels and decreases remodeling and PVR in rats with chronic-hypoxic pulmonary hypertension, partially via a tyrosine-kinase-dependent mechanism. These drugs appear safe in humans and may be useful PAH therapies, alone or in combination.
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PMID:The NO - K+ channel axis in pulmonary arterial hypertension. Activation by experimental oral therapies. 1471 30

Impairment of erectile function compromises quality of life in millions of men and their partners, many of whom prefer to suffer in silence. It is important to maintain an elevated index of clinical suspicion in patients with erectile dysfunction (ED) risk factors (e.g. hypertension, diabetes, coronary heart disease). There remains a high rate of voluntary discontinuation of therapy associated with most treatment modalities. Since the introduction of sildenafil, a greater awareness and openness regarding the epidemiology and treatment of male erectile dysfunction has emerged. The development of newer and potentially more efficacious phosphodiesterase type 5 (PDE5) inhibitors will serve to treat an even greater number of patients, allowing once daily and more convenient dosing. An increased understanding of the physiological principles of penile erection has allowed the development of novel oral pharmacological therapies. The new agents offer a potential benefit in a broader range of patients and clinical situations. They may provide a more acceptable alternative than other more invasive options (intracavernosal/urethral injection, implant surgery). The dopamine agonist apomorphine acts on the central control of penile erection to allow a sublingual preparation to produce a prompt response. It is not contraindicated in patients on nitrate medication for coronary artery disease, or in patients with depression or on antidepressants. As with any other treatment, the clinician's responsibility in the care of ED patients does not end with the writing of a prescription. Adequate education and follow-up are needed to optimize the efficacy and safety of oral ED therapy. Furthermore, patients and their partners need to be advised that the agents are not effective in the absence of sexual stimulation. Communicating with both the patient and his partner in a discreet, non-judgmental manner that fosters the physician-patient alliance can facilitate the recognition and treatment of ED.
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PMID:Update on oral treatments for male erectile dysfunction. 1509 34

Erectile dysfunction (ED) is often a marker for serious underlying cardiovascular disease (CVD), and cardiologists are increasingly involved in the care of men with ED. It is important to ask specifically about ED when evaluating men with CVD, since they may be embarrassed to volunteer this information. During the clinical workup, it is also important to check for contributing factors to ED such as diabetes, depression, stress, alcohol abuse, and cardiovascular risk factors. Patients should be advised that many treatment options are available for ED, including the phosphodiesterase type 5 (PDE5) inhibitors. The PDE5 inhibitors are safe and effective in most patients with CVD, including those taking multiple antihypertensive drugs. Furthermore, they have no deleterious effect on exercise capacity, heart rate, or extent of exercise-induced ischemia. In the future, the PDE5 inhibitors may have a role in reducing pulmonary hypertension in persons with primary pulmonary arterial hypertension (PAH) or congestive heart failure. The one major precaution for men taking PDE5 inhibitors is to avoid concomitant administration of therapeutic and recreational nitrate preparations. Patients with chest pain suggestive of a heart attack need to inform emergency room (ER) personnel if they are taking a PDE5 inhibitor. Similarly, before giving nitrates, ER personnel need to ask patients if they have used PDE5 inhibitors. Nitrates should not be given for at least 24 h after a patient uses sildenafil or vardenafil and at least 48 h after a patient uses tadalafil.
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PMID:Role of the cardiologist: clinical aspects of managing erectile dysfunction. 1511 89

Erectile dysfunction (ED) is a common condition with a significant effect on the quality of life. The prevalence of ED rises with increasing age and other conditions (hypertension, diabetes, ischaemic heart disease, hypercholesterolaemia and depression). The MALES study is one of the largest epidemiological surveys to investigate the prevalence of ED. This study included 27839 patients spanning eight countries. In addition to the MALES study, we review the emerging link between lower urinary tract symptoms (LUTS), benign prostatic hypertrophy (BPH) and ED, including the effect of BPH treatment on sexual function. Preliminary data from the MALES II study shows a significant cascade effect in the treatment seeking behaviour and treatment adherence of patients taking sildenafil for ED. We explore the possible reasons behind the discontinuation of oral phosphodiesterase inhibitors prescribed for the long-term treatment of ED.
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PMID:Erectile dysfunction: an underdiagnosed condition associated with multiple risk factors. 1517 Dec 25

Sildenafil, a potent type 5 nucleotide-dependent phosphodiesterase (PDE) inhibitor, has been recently proposed as a therapeutic tool to treat or prevent pulmonary artery hypertension (PAHT). We thus studied the effect of sildenafil on both the calcium signaling of isolated pulmonary artery smooth muscle cells (PASMCs) and the reactivity of pulmonary artery (PA) obtained from chronic hypoxia (CH)-induced pulmonary hypertensive rats compared with control (normoxic) rats. CH rats were maintained in an hypobaric chamber (50.5 kPa) for 3 wk leading to full development of PAHT. Intracellular calcium concentration ([Ca2+]i) was measured in PASMCs loaded with the calcium fluorophore indo 1. Unlike in control rats, sildenafil (10-100 nM) decreased the resting [Ca2+]i value in PASMCs obtained from CH rats. In PASMCs from both control and CH rats, sildenafil concentration dependently inhibited the [Ca2+]i response induced by G-coupled membrane receptor agonists such as angiotensin II and phenylephrine but had no effect on the amplitude of the [Ca2+]i response induced by caffeine. Sildenafil (0.1 nM-1 microM) concentration dependently reduced basal PA tone that is present in CH rats and relaxed PA rings precontracted with phenylephrine in both control and CH rats. These data show that sildenafil is a potent pulmonary artery relaxant in CH rats and that it normalizes CH-induced increases in resting [Ca2+]i and basal tone. Consequently, pharmacological inhibition of sildenafil-sensitive PDE5 downregulates the Ca2+ signaling pathway involved in this model of pulmonary hypertension.
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PMID:Sildenafil alters calcium signaling and vascular tone in pulmonary arteries from chronically hypoxic rats. 1515 72

Erectile dysfunction (ED) is a common problem in men over 40-50 years of age. Risk factors include: diabetes, lipid abnormalities, smoking, hypertension, obesity, and lack of physical activity. Oral phosphodiesterase-5 inhibitors appear effective and safe in most cardiac patients.
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PMID:Erectile dysfunction in the cardiac patient. 1516 92

Pulmonary hypertension (PH) is a disease of various origins. Nitric oxide-a potent vasodilator-is a key player of pulmonary vasoregulation. Nitric oxide signaling is mainly mediated by the guanylate cyclase/cyclic guanylate monophosphate pathway. The effects of this second messenger system are limited by enzymatic degradation through phosphodiesterases (PDEs). Recently, beneficial effects of the oral PDE-5 inhibitor sildenafil (originally approved for the treatment of erectile dysfunction) were reported for the treatment of PH. We provide a brief overview of the experimental and clinical application of PDE inhibitors in the field of PH. In particular, studies reporting the clinical effectiveness of sildenafil are highlighted. This agent, despite oral application, displays characteristics of a pulmonary selective vasodilator. In addition, evidence shows that sildenafil is operative mainly in the vasculature of well-ventilated areas of the lung. However, to date, controlled randomized trials proving the efficacy of this approach for the treatment of pulmonary arterial hypertension are lacking. The results of such studies have to confirm the current encouraging findings before recommendations regarding the use of PDE-5 inhibitors as a new treatment for PH can be made.
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PMID:Nitric oxide pathway and phosphodiesterase inhibitors in pulmonary arterial hypertension. 1519 81

Erectile dysfunction (ED) is common in cardiac patients and shares the same risk factors--smoking, hypertension, hyperlipidaemia and diabetes mellitus. Sexual activity is not unduly stressful to the heart and, providing patients are properly assessed using established guidelines, sexual intercourse can be enjoyed without increased risk. The treatment of ED in patients with cardiovascular disease has been transformed by the introduction of the oral phosphodiesterase type 5 inhibitors, the first of which was sildenafil. Success in restoring erectile function is possible in up to 80% of patients (depending on the aetiology) with minimal adverse effects. A synergistic hypotensive effect with nitrates, and almost certainly nicorandil, is the only major contraindication. ED in asymptomatic patients may be a marker of silent vascular disease or increased vascular risk factors and should alert the physician to the need for cardiac risk screening. ED is common in patients with cardiovascular disease and should be routinely enquired about. ED is a distressing condition for the man and his partner, and severely impairs quality of life. Patients with cardiovascular disease and patients with diabetes represent the largest group of patients with ED, the majority of whom benefit from the drug therapies currently available. Addressing ED in patients with cardiovascular disease can lead to a substantial improvement in quality of life and success is not difficult to achieve.
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PMID:Treatment of erectile dysfunction in patients with cardiovascular disease : guide to drug selection. 1523 91

Chronic pulmonary hypertension (PHT) is characterized by permanently increased pulmonary artery pressure. Diagnostic criteria are a mean pulmonary arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. Pulmonary arterial hypertension is characterized by progressive obliteration of the pulmonary vascular bed, which results in progressive right heart failure and death. Pathologic processes behind the complex vascular changes associated with PHT include vasoconstrictor/vasodilator imbalance, thrombosis, misguided angiogenesis and inflammation. The function of the pulmonary endothelium is altered with decreased production of vasodilators such as prostacyclin and nitric oxide and an increased production of endothelins, finally resulting in pulmonary vascular remodelling. A new diagnostic classification of pulmonary hypertension (PHT) was proposed at the World Health Organization (WHO) Pulmonary Hypertension Meetings held in Evian in 1998 and in Venice in 2003. This classification reflects recent advances in the understanding of pulmonary hypertensive diseases. Depending on the underlying disease and the localization of the vascular lesion, five different subgroups of PHT are formed. An exact diagnostic classification is necessary for application of the current treatment options for the different forms of PHT. Target of therapy is besides avoiding local thrombosis by anticoagulation and treatment of vasoconstriction, the prevention of vascular remodelling. For patients with advanced pulmonary arterial hypertension (PAH; NYHA stages III and IV) treatment with prostanoids (inhalative, oral, subcutaneous or intravenous), with endothelin-receptor antagonists or with a phosphodiesterase inhibitor can be indicated. Whether initial or adjunct combined therapy provides additional clinical benefits to patients with severe pulmonary arterial hypertension needs further investigation, but first results are promising.
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PMID:[Pulmonary hypertension. Pathophysiology and current concepts of medication therapy]. 1527 94

The past decade has realized remarkable advances in the treatment of pulmonary arterial hypertension (PAH), a progressive and potentially fatal disease. A small proportion of patients will have a dramatic hemodynamic response to acute vasodilator testing performed at the time of right heart catheterization and may be candidates for calcium channel blocker therapy. The vast majority of patients with PAH will not benefit from calcium channel blockers and should be treated with one of the three US Food and Drug Administration-approved therapies for PAH; bosentan, treprostinil, or epoprostenol. Because of the ease of administration relative to other therapies, the majority of patients with functional class III symptoms should be treated with the oral nonselective endothelin antagonist bosentan. Randomized controlled trials with treprostinil have demonstrated improvements in exercise endurance and hemodynamics. Patients who are critically ill, with functional class IV symptoms, should be started on epoprostenol because it is the most rapidly effective therapy. Intravenous epoprostenol improves exercise endurance, quality of life, hemodynamics, and survival in PAH. Investigational therapies on the horizon include phosphodiesterase inhibitors, prostacyclin analogues with alternative delivery routes (eg, inhaled, oral), and selective endothelin A receptor antagonists. The future of PAH therapy will likely include combinations of these therapies based on the multiple mechanisms of action.
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PMID:Pulmonary Arterial Hypertension: New Management Options. 1549 62


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