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

Erectile dysfunction (ED) and depression are highly prevalent conditions and frequently occur concomitantly in predisposed individuals. Men with ED and depression are also likely to have other comorbid conditions, including diabetes, hypertension, and heart disease. Because ED is also a common adverse effect of some medications for these conditions, patients are frequently noncompliant with treatment. Sildenafil citrate (Viagra) is effective in treating ED of a broad range of etiologies, suggesting that it may be equally beneficial in patients with ED that is associated with depressive symptoms and in those with ED resulting from serotonergic reuptake inhibitor (SRI) antidepressant treatment. We review the results of 3 randomized, placebo-controlled trials and a retrospective analysis of data pooled from 10 clinical trials that examine the efficacy of sildenafil in treating ED associated with depression and as an adverse effect of SRI treatment. The results suggest that sildenafil is efficacious as a first-line treatment for ED in men with untreated minor depression, in men with ED that is refractory to successful SRI treatment of depression, and in those whose depression was successfully treated but who developed ED as a consequence of SRI treatment. Given the complex interrelations among ED, depression, and other comorbid conditions, the key to proper management is a comprehensive evaluation, including sexual function, and an accurate differential diagnosis.
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PMID:Depression, antidepressant therapies, and erectile dysfunction: clinical trials of sildenafil citrate (Viagra) in treated and untreated patients with depression. 1241 34

In Germany, some 4-6 million men, including 1.2 million diabetics, suffer from erectile dysfunction (ED). Various other diseases including heart disease, hypertension, arteriosclerosis, hyperlipidemia, endocrine disorders, chronic renal insufficiency, prior radical prostatectomy, neurological diseases, trauma and the abuse of alcohol, tobacco, and side effects of medications, are frequently associated with ED. Medical history, clinical examination, routine blood chemistry and sexual hormone levels may help clarify the etiology of ED. Normally, relaxation of the smooth muscles of the corpus cavernosum--mediated by cGMP and cAMP--together with dilatation of penile arteries and occlusion of venous outflow, results in an erection. The oral type V phosphodiesterase inhibitor, Sildenafil, or prostaglandin E1 injection elevates the cGMP and cAMP levels, respectively. Other therapeutic options include mechanical aids, surgery, hormone replacement or sublingual apomorphine. Since 1998, Sildenafil, an effective, simple and safe oral treatment, has been available.
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PMID:[Erectile dysfunction. An important manifestation of autonomic diabetic neuropathy]. 1253 21

Sildenafil is the first oral therapeutic agent for erectile dysfunction. Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase (PDE-5). Penile erection involves relaxation of the corpus cavernosum, an event mediated by NO and cGMP. The biological actions of cGMP are terminated by phosphodiesterase enzymes and PDE-5 is the major cGMP metabolising enzyme in this tissue. Sildenafil is relatively safe compared to erection injectables because it does not relax on isolated human corpus cavernosum, and does not cause priapism. Due to the tendency of abuse of sildenafil, its adverse cardiovascular associations with myocardial infaraction, ventricular arrhythmia and hypertension need to be alerted.
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PMID:[Mode of action of sildenafil]. 1256

Smoking is associated with endothelial dysfunction. The purpose of this study was to determine the effect of sildenafil, an inhibitor of phosphodiesterase type 5 (PDE5), on endothelial function in smokers. We evaluated the forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, before and after oral sildenafil administration (100 mg) with a strain-gauge plethysmograph in 10 young healthy male smokers and 10 young healthy male nonsmokers. FBF response to ACh was lower in smokers than in nonsmokers. The vasodilatory effects of SNP were similar in both groups. Sildenafil increased the FBF response to ACh from 9.3+/-2.0 to 12.5+/-3.5 mL/min per 100 mL tissue in smokers and from 12.6+/-5.6 to 19.6+/-8.4 mL/min per 100 mL tissue in nonsmokers, and it increased the response to SNP from 13.3+/-3.9 to 15.1+/-4.3 mL/min per 100 mL tissue in smokers and from 14.8+/-5.2 to 18.4+/-6.0 mL/min/100 mL tissue in nonsmokers (P<0.05 for all). The ratio of maximal ACh-stimulated FBF expressed as a ratio of maximal SNP-stimulated FBF significantly increased after administration of sildenafil in both groups. Infusion of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, abolished sildenafil-induced augmentation of the FBF response to ACh in both groups. The findings suggest that endothelial function is impaired in smokers compared with that in nonsmokers, that inhibition of PDE5 by sildenafil significantly increases nitric oxide-mediated vasodilation, and that the activities of PDE5 in smokers and nonsmokers may be similar.
Hypertension 2003 May
PMID:PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers. 1269 18

In recent years, the better understanding of the pathobiology and pathogenesis of pulmonary arterial hypertension (PAH) has led to the development of new drugs for its treatment. Epoprostenol, which was the first drug approved for PAH, has shown an improvement in the survival at 3 years in patients with primary pulmonary hypertension. Recently, the Food and Drug Administration has approved two new compounds, Bosentan (an oral, non-selective endothelin receptor blocker) and Treprostinil (a subcutaneous prostacyclin analog). At least three multicenter, international studies are currently in progress. These studies include the use of a diet supplement rich in arginine (nitric oxide precursor), the evaluation of an endothelin A-receptor blocker (Sitaxsentan), and the evaluation of Sildenafil (a 5-phosphodiesterase inhibitor). As long as research continues to scrutinize the pathogenesis of this disease, clues to possible new therapies are warranted.
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PMID:[What is new in the treatment of pulmonary artery hypertension?]. 1296 61

Cardiologists are seeing increasing numbers of patients with erectile dysfunction (ED), which frequently coexists with cardiovascular disease. The pharmacologic profile of the new class of phosphodiesterase (PDE) inhibitors-specifically PDE5 inhibitors-and their potential effects on hemodynamic variables have therefore become significant factors in therapeutic decision making. Most of the published data linking PDE5 inhibitor effects and cardiovascular disease relate to sildenafil, although >or=2 new agents are in various stages of development and clinical trials. Sildenafil and other PDE5 inhibitors act on vascular smooth muscle, predominantly in the corpus cavernosum. PDE5 is not found in cardiomyocytes, and no effect of PDE5 inhibition on cardiac contractility has been demonstrated. On the basis of a safety database comprising thousands of men with ED, sildenafil has demonstrated minimal adverse effects in men with stable ischemia, hypertension, and/or severe coronary artery disease. Sildenafil has modest effects on hemodynamic variables and has been shown to increase coronary artery flow reserve. Alone or combined with >or=1 antihypertensive medication, sildenafil did not increase the incidence of adverse events or hypotensive episodes. Sildenafil-associated decreases in systolic and diastolic blood pressure, the result of its vasodilator activity, have been modest. Sildenafil has decreased both elevated pulmonary vascular resistance and elevated pulmonary artery pressures in patients with pulmonary vascular disease. Beneficial changes in hemodynamics have been observed with the use of sildenafil in patients with congestive heart failure with underlying ischemic and other dilated cardiomyopathies. No association between sildenafil and increased cardiovascular morbidity or mortality has emerged in analyses of clinical trial data.
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PMID:Sildenafil in patients with cardiovascular disease. 1460 21

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

This was a double-blind, placebo-controlled, flexible-dose study of the efficacy and safety of sildenafil in men with erectile dysfunction (ED) and clinically stable coronary artery disease (CAD). Patients were randomized to receive sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of the International Index of Erectile Function (IIEF). Secondary outcomes included the other IIEF questions and functional domains, the Life Satisfaction Checklist, the Erectile Dysfunction Inventory of Treatment Satisfaction, 2 global efficacy assessment questions, and intercourse success rate. By week 12, sildenafil-treated patients (n = 70) showed significant improvements on questions 3 and 4 compared with placebo-treated patients (n = 72; p <0.01). Larger percentages of sildenafil-treated patients reported improved erections (64%) and improved intercourse (65%) compared with placebo-treated patients (21% and 19%, respectively). Sildenafil-treated patients were highly satisfied with treatment and their sexual life compared with placebo-treated patients. Forty-seven percent of sildenafil- and 32% of placebo-treated patients experienced adverse events, including transient headache, hypertension, flushing, and dyspepsia. There were no serious drug-related cardiovascular effects. Thus, sildenafil is an effective and well-tolerated treatment for ED in men with CAD. Sildenafil was not associated with additional safety risks in this patient population.
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PMID:Efficacy and safety of sildenafil citrate in men with erectile dysfunction and stable coronary artery disease. 1471 38

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

Seven patients, aged between 50 and 69 years, had typical features of nonarteritic anterior ischemic optic neuropathy (NAION) within 36 hours after ingestion of sildenafil citrate (Viagra) for erectile dysfunction. Six patients had vision loss within 24 hours after use of the agent. Final visual acuity in the affected eye ranged from 20/20 to light perception. Both eyes were affected in one individual. All affected individuals had pre-existing hypertension, diabetes, elevated cholesterol, or hyperlipidemia. Seven similar cases have been previously reported. Sildenafil may provoke NAION in individuals with an arteriosclerotic risk profile.
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PMID:Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (viagra): a report of seven new cases. 1651 58


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