A combination of oralSildenafil Citrate (Viagra) and beraprost ameliorates pulmonary hypertension in rats.

Sildenafil, an oral phosphodiesterase type-5 inhibitor, has vasodilatory effects through a cyclic guanosine 3', 5'-monophosphate-dependent mechanism, whereas beraprost, an oral prostacyclin analog, induces vasorelaxation through a cAMP-dependent mechanism. We investigated whether the combination of oralSildenafil Citrate (Viagra) and beraprost is superior to each drug alone in the treatment of pulmonary hypertension. Rats were randomized to receive repeated administration of saline, sildenafil, beraprost, or both of these drugs twice a day for 3 weeks. Three weeks after monocrotaline (MCT) injection, there was significant development of pulmonary hypertension. The increases in right ventricular systolic pressure and ratio of right ventricular weight to body weight were significantly attenuated in theSildenafil Citrate (Viagra) and Beraprost groups. Combination therapy withSildenafil Citrate (Viagra) and beraprost had additive effects on increases in plasma cAMP and cyclic guanosine 3', 5'-monophosphate levels, resulting in further improvement in pulmonary hemodynamics compared with treatment with each drug alone. Unlike MCT rats given saline, sildenafil, or beraprost alone, all rats treated with both drugs remained alive during 6-week follow-up. These results suggest that combination therapy with oralSildenafil Citrate (Viagra) and beraprost attenuates the development of MCT-induced pulmonary hypertension compared with treatment with each drug alone

Improvement in emotional well-being and relationships of users of sildenafil.

PURPOSE: We estimated the association ofSildenafil Citrate (Viagra) use with erectile function, relationship with sexual partner, functional status and emotional well-being in men with Erectile Dysfunction. MATERIALS AND METHODS: Letters were mailed to eligible patients at a university hospital urology and internal medicine clinic, and university affiliated community primary care clinics by the primary care provider or urologist inviting them to participate in the study. Of the eligible sample 124 men (53%) completed and returned a survey, including 85 who reported currentSildenafil Citrate (Viagra) use. Change scores in these patients were calculated using the International Index of Erectile Function, marital interaction scale from the Cancer Rehabilitation Evaluation System Short Form, 5-item emotional well-being scale of the RAND 36-Item Health Survey and 12-Item Short Form Health Survey. RESULTS:Sildenafil Citrate (Viagra) users reported an 88% increase in erectile function scores, 60% increase in overall sexual satisfaction and 36% increase in intercourse satisfaction related to the use ofSildenafil Citrate (Viagra) (p <0.001). Of the respondents 38% indicated that usingSildenafil Citrate (Viagra) had definitely improved quality of life. Likewise 29% of respondents indicated that usingSildenafil Citrate (Viagra) had definitely improved the relationship with their partner. WithSildenafil Citrate (Viagra) there was a statistically significant improvement in the scores of erectile and sexual function (p <0.001), sexual partner relationship (p = 0.007) and emotional well-being (p <0.001). In a multivariate model improved erectile function and sexual partner relationship were each significantly associated with improved emotional well-being (R2 = 0.20, p <0.001). CONCLUSIONS:Sildenafil Citrate (Viagra) users reported significant improvements in erectile and sexual function that were associated with positive changes in emotional well-being and the sexual partner relationships with their sexual partner

Effect of PDE5 inhibition on coronary hemodynamics in pacing-induced heart failure.

Inhibition of phosphodiesterase type 5 (PDE5) can relax systemic and coronary vessels by causing accumulation of cGMP. Both the endothelial dysfunction with decreased nitric oxide production and increased natriuretic peptide levels in congestive heart failure (CHF) have the potential to alter cGMP production, thereby influencing the response to PDE5 inhibition. Consequently, this study examined the effects of PDE5 inhibition withSildenafil Citrate (Viagra) in dogs with CHF produced by rapid ventricular pacing. CHF resulted in decreases of left ventricular (LV) systolic pressure, coronary blood flow, and the maximal first time derivative of LV pressure (LV dP/dt(max)) at rest and during treadmill exercise compared with normal, whereas resting LV end-diastolic pressure increased from 10 +/- 1.4 to 23 +/- 1.4 mmHg.Sildenafil Citrate (Viagra) (2 and 10 mg/kg per os) caused a 5- to 6-mmHg decrease of aortic pressure (P < 0.05), with no change of heart rate, LV systolic pressure, or LV dP/dt(max).Sildenafil Citrate (Viagra) caused no change in coronary flow or myocardial oxygen consumption in animals with CHF at rest or during exercise. In contrast to findings in normal animals,Sildenafil Citrate (Viagra) did not augment endothelium-dependent coronary vasodilation in response to acetylcholine in animals with CHF. Furthermore, Western blotting showed decreased PDE5 protein expression in myocardium from failing hearts. These findings demonstrate that PDE5 contributes little to regulation of coronary hemodynamics in CHF

Systemic and splanchnic haemodynamic effects ofSildenafil Citrate (Viagra) in an in vivo animal model of cirrhosis support for a risk in cirrhotic patients.

OBJECTIVES:Sildenafil Citrate (Viagra) is a selective inhibitor of the cGMP-specific phosphodiesterase type V (PDE-V) in the corpus cavernosum. PDE-V is also present in the mesenteric artery. Cirrhosis is complicated by a splanchnic vasodilation attributed to a local overproduction of nitric oxide (NO). AsSildenafil Citrate (Viagra) potentiates the effects of NO, it may further decrease mesenteric vascular tone and increase portal venous blood flow. The aim is to evaluate the effects ofSildenafil Citrate (Viagra) on the systemic and splanchnic haemodynamics in an experimental model of cirrhosis. METHODS: Secondary biliary cirrhosis was induced in male Wistar rats by common bile duct ligation (CBDL, n=8); control rats were sham-operated (sham, n=7). The mean arterial pressure (MAP), portal venous pressure (PVP) and arterial mesenteric blood flow (MBF) were measured after intramesenteric (0.01-10 mg/kg) and after intravenous (i.v.) (0.01-10 mg/kg) administration of sildenafil. RESULTS: Baseline PVP was significantly higher in CBDL than in sham rats, whereas baseline MAP tended to be lower and MBF tended to be higher in CBDL compared with sham rats. Both intramesenteric and i.v. injection ofSildenafil Citrate (Viagra) significantly decreased MAP and increased MBF and PVP in a dose-dependent way. The decrease in MAP was significantly less important in CBDL than in sham rats. The increase in MBF was importantly lower in CBDL than in sham rats. PVP tended to increase more significantly in sham rats than in CBDL. CONCLUSION:Sildenafil Citrate (Viagra) increases MBF and PVP and induces systemic hypotension. The effects are less pronounced in cirrhosis, suggesting vascular hyporesponsiveness to sildenafil. Although the rise in PVP in cirrhotic animals is smaller than in controls, it may present a risk for haemorrhagic complications. Further studies are necessary before prescribingSildenafil Citrate (Viagra) to patients with cirrhosis

The effects of Sildenafil Citrate (Viagra) on the isolated rat aorta: comparative in vitro study

OBJECTIVE: Sildenafil, an inhibitor of cGMP-specific phosphodiesterase 5 (PDE5), is currently being used as oral therapy for penile Erectile Dysfunction. The aim of this study was to investigate the relaxing effect ofSildenafil Citrate (Viagra) on vascular tissue and compare it with the known vasodilatator agents, sodium nitroprusside and acetylcholine. METHOD: Rat thoracic aorta samples were cut into rings, mounted on steel hooks, and immersed in aerated Krebs solution maintained at 37 degree C. Isometric responses were recorded by strain gauge transducers connected to a polygraph. Graded relaxations were induced using increasing concentrations of acetylcholine sodium nitroprusside and sildenafil. RESULTS: The agents all does-dependently relaxed rat aorta strips. The relaxing potential ofSildenafil Citrate (Viagra) was found to be similar to sodium nitroprusside, but higher than acetylcholine. CONCLUSIONS: In the absence of regulatory mechanisms, Sildenafil Citrate (Viagra) has noticeable vasodilatatory effect in vitro

Quality control in the urologist's practice Erectile Dysfunction as an example of a multi-centered approach to documenting treatment results in urologist practices.

Of 517 urologist practices approached, 93% participated in a pilot study on the quality of care in the treatment of Erectile Dysfunction (ED). Treatment modalities and satisfaction were documented for 10,750 ED patients in 2002-at a time when vardenafil and tadalafil had not yet been officially approved. Psychological factors (55%), BPH (42%), and hypertension (33%) were given as the most prevalent ED risk factors; 82% of the patients received sildenafil, 20% apomorphine, 12% yohimbine, and 10% intracavernous alprostadil. Of the patients, 81% were satisfied or very satisfied with one of the treatment options offered and 85% and more were satisfied or very satisfied with sildenafil's onset of action, duration of action, efficacy, and tolerability. Of the physicians, 97% rated the opportunity to compare their own treatment results with other urologists' results as important or very important

Comparison of clinical trials with sildenafil, vardenafil and tadalafil in Erectile Dysfunction.

Erectile Dysfunction (ED) affects up to 50% of men, between 40 and 70years of age. In the first major trial ofSildenafil Citrate (Viagra) in ED, at 24weeks, improved erections were reported by 77 and 84% of men takingSildenafil Citrate (Viagra) 50 and 100mg, respectively. Subsequently,Sildenafil Citrate (Viagra) has been reported to be effective in men with ED associated with diabetes and prostate cancer, and in psychogenic ED.Sildenafil Citrate (Viagra) is safe in men with coronary artery disease, provided it is not used with the nitrates (a contraindication). The most commonly reported adverse effects withSildenafil Citrate (Viagra) are headache, flushing and dyspepsia. Vardena-fil is more potent and more selective thanSildenafil Citrate (Viagra) at inhibiting phosphodiesterase-5. Vardenafil is similarly effective toSildenafil Citrate (Viagra) in the treatment of ED. The only advantage that vardenafil has overSildenafil Citrate (Viagra) is that it does not inhibit phosphodiesterase-6 to alter colour perception, a rare side effect which sometimes occurs with sildenafil. Tadalafil has a longer duration of action thanSildenafil Citrate (Viagra) and vardenafil. Tadalafil is similarly effective as sildena-fil in the treatment of ED. In comparison studies, tadalafil is preferred toSildenafil Citrate (Viagra) (50/100mg) by men with ED, possibly because of its longer duration of action. Of the phosphodiesterase inhibitors, tadalafil may displace sild-enafil as the drug of choice among men with ED

Risk factors in predicting a poor response to Sildenafil Citrate (Viagra) in elderly men with Erectile Dysfunction.

OBJECTIVE: To assess the clinical efficacy ofSildenafil Citrate (Viagra) and the potential predictors of poor response toSildenafil Citrate (Viagra) in elderly patients with Erectile Dysfunction (ED). PATIENTS AND METHODS: The study included 162 patients (aged > or = 60 years) treated withSildenafil Citrate (Viagra) for at least 8 weeks; all patients were evaluated with a history, physical examination, measurement of total testosterone and a pharmacological erection test. Sexual function before and 8 weeks after treatment was assessed using the self-administered International Index of Erectile Function (IIEF). Treatment was considered successful when the patient attained a higher grade on the erectile function (EF) domain score, and an affirmative response to the overall assessment question. Factors influencing treatment outcome were evaluated by univariate and multivariate statistical analysis. RESULTS: The overall efficacy withSildenafil Citrate (Viagra) was 47% (76/162). On univariate analysis, uncontrolled diabetes, current smoking, hypogonadism (<3 microg/L testosterone) and low pretreatment EF domain score (<17) were selected as predictors of a poor response. On multivariate logistic regression, a low pretreatment EF domain score was the strongest independent prognostic factor for a poor response (odds ratio 2.25, 95% confidence interval, 1.45-7.33), and this was followed by hypogonadism (1.89, 1.12-3.16) and current smoking (1.34, 1.04-3.52). CONCLUSION: In a real clinical setting,Sildenafil Citrate (Viagra) was effective for about half of the elderly men. The baseline EF domain score, hypogonadism and current smoking were significantly associated with failure of sildenafil. These results suggest that modifying reversible risk factors, e.g. stopping smoking and replacing testosterone, would be beneficial in augmenting the efficacy ofSildenafil Citrate (Viagra) in elderly men