Synergistic effects ofSildenafil Citrate (Viagra) on relaxation of rabbit and rat cavernosal smooth muscles when combined with various vasoactive agents.

OBJECTIVE: To evaluate which vasoactive agents have synergistic effects on the cavernosal smooth muscles of rabbits and rats when the agents are combined with sildenafil. MATERIALS AND METHODS: Relaxation responses of cavernosal smooth muscle to single agents (phentolamine, moxisylyte, sodium nitroprusside, forskolin, vasoactive intestinal peptide, VIP, papaverine and sildenafil) in the rabbit, and prostaglandin-E1 andSildenafil Citrate (Viagra) in the rat, and to combinations of each agent plus sildenafil, were assessed in vitro. The response toSildenafil Citrate (Viagra) of the rabbit strips with and without incubation with l-arginine (1 mmol/L) for 20 min was also evaluated. The effective concentrations for a half-maximal response of single agents and combination solutions were compared. RESULTS: All single agents induced concentration-dependent relaxation of the rabbit and rat cavernosal smooth muscles. There was significant synergism on rabbit cavernosal smooth muscle when theSildenafil Citrate (Viagra) was combined with forskolin, sodium nitroprusside, VIP or phentolamine. There was also significant synergism withSildenafil Citrate (Viagra) plus prostaglandin-E1 in rat cavernosal muscles. There were no synergistic effects of combinations ofSildenafil Citrate (Viagra) plus moxisylyte, papaverine or l-arginine. CONCLUSIONS: These results suggest potentially effective combined therapies ofSildenafil Citrate (Viagra) and intraurethral or intracavernosal prostaglandin-E1, intracavernosal forskolin or VIP, or oral phentolamine for patients with Erectile Dysfunction who have no success after monotherapy with these agents

Sildenafil for treatment of severe pulmonary hypertension and commencing right-heart failure

Pulmonary hypertension (PHT) is mainly explained by four underlying pathophysiological phenomena: 1. Vasoconstriction, 2. reduction of pulmonary vascular bed, 3. reduction in vessel elasticity, and 4. obliteration of the vessel lumen by thrombotic material and subsequent cellular alterations of the vessel wall (vascular remodeling). Chronic right heart load is thus a consequence of increased pulmonary pressure and vascular resistance. Main targets of advanced therapeutic strategies are therefore first: resolution of chronically increased vascular tone by smooth muscle cell relaxation (vasodilators), second: reversal of vascular remodeling and third: prevention from pulmonary embolization and/or in-situ thrombosis (chronic anticoagulation). Long term administration of high dose calcium channel blockers (though operative only in a minority of 10 - 15 % of all patients), prostanoids (eg. prostacyclin, iloprost), and the recently approved unselective oral endothelin antagonist bosentan are regarded as established medical therapies for treatment of chronic PHT. However, applicability of these substances can be limited by potentially serious adverse events and/or necessity for elaborate parenteral application. Recent data are indicative for a strong pulmonary vasodilative potency of the selective phosphodiesterase-5 (PDE5) inhibitor sildenafil. Smaller clinical studies and numerous case reports underline the good tolerability of this orally applied substance in various form of PHT. Based on these encouraging results, the simple availability, and the low costs (in comparison to "established therapies") of the drug,Sildenafil Citrate (Viagra) is currently widely used in an "off-label" indication for treatment of PHT. Controlled randomized studies have to confirm the current findings, before general recommendations regarding the use ofSildenafil Citrate (Viagra) for treatment of PHT can be made

Coronary artery flow reserve in diabetics with Erectile Dysfunction using sildenafil.

BACKGROUND: Diabetics with Erectile Dysfunction have a high prevalence of microvascular disturbance of the coronary circuit as measured by coronary flow reserve (CFR). PURPOSE: We aimed to evaluate the effects of the phosphodiesterase 5 inhibitorSildenafil Citrate (Viagra) on CFR in diabetics with Erectile Dysfunction. METHODS: Diabetics seeking diabetes refinement therapy were screened for vascular or neurogenic Erectile Dysfunction which was confirmed in 43 patients. No ischemic ECG changes were found in any of the ECG stress tests at the 100 W level. Cardiologic examinations raised suspicion of coronary artery disease in 16 patients; coronary angiography confirmed severe coronary artery lesions in 12, who were excluded from further analysis. CFR measurements were not possible in 10 participants. The 21 diabetics eligible for CFR measurements aged 60 years (50-69) had known diabetes for 11 years (3-30) and a BMI of 27 kg/m2 (24-36). CFR of the left anterior descending artery was assessed at baseline and 1 hour after 50 mg sildenafil, using transthoracic Doppler echocardiography. RESULTS: Baseline CFR was at the lower level of the normal range (median 245%, range 210 - 490%). AfterSildenafil Citrate (Viagra) administration, CFR decreased insignificantly (DeltaCFR -10%, p = 0.3). Patients with a BMI > 25 kg/m2 and left ventricular hypertrophy exhibited the highest reduction of CFR after sildenafil. No decrease of CFR below 200 % was observed. Systemic blood pressure dropped from 130/80 mmHg to 120/72 mmHg (p < 0.002). CONCLUSIONS: Diabetics with Erectile Dysfunction exhibit a CFR in the lower normal range indicating severe microvascular disturbance.Sildenafil Citrate (Viagra) did not alter CFR in those patients. A high prevalence of severe coronary macroangiopathy was identified in asymptomatic diabetic patients screened for contraindications forSildenafil Citrate (Viagra)

Sildenafil Citrate (Viagra) on nitrergic transmission in anococcygeus muscles from the urogenital system of male and female mice.

The effects ofSildenafil Citrate (Viagra) on nitrergic relaxations were compared in anococcygeus muscles from male and female mice. In muscles from both sexes,Sildenafil Citrate (Viagra) (10-300 nM) produced a weak, direct relaxation of carbachol-induced tone, and increased both the amplitude and duration of nitrergic relaxations. The most marked effect was on nitrergic duration (300-400% increase with 300 nM sildenafil); no differences in potency were observed between male (EC(50), 30 nM) and female (EC(50), 25 nM). The rate of onset for potentiation of nitrergic duration was similar in both sexes; but, on washout, the effects ofSildenafil Citrate (Viagra) declined more slowly in the male muscle. Relaxations to both nitric oxide (NO) and sodium nitroprusside were also increased in amplitude and duration by 50 nM sildenafil, while those to forskolin and papaverine were unaffected. The results demonstrate thatSildenafil Citrate (Viagra) causes a similar, potent and selective potentiation of nitrergic transmission in urogenital smooth muscle from both male and female mice

Efficacy and factors associated with successful outcome of Sildenafil Citrate (Viagra) use for Erectile Dysfunction after radical prostatectomy.

OBJECTIVES: To assess the efficacy and factors associated with successful treatment of Sildenafil Citrate (Viagra) for Erectile Dysfunction after radical prostatectomy (RP). METHODS: Of the 470 patients who underwent RP at our institution between July 1998 and January 2000, 227 (48%) sought treatment for Erectile Dysfunction, and 174 (37%) were prescribed Sildenafil Citrate (Viagra). The starting dose was 50 mg, which was increased to 100 mg if the patient did not have a positive response. Of the 174 patients, 104 (59.8%) had undergone a bilateral nerve-sparing (NS) procedure, 28 (16.1%) had undergone a unilateral NS procedure, and 42 (24.1%) had undergone a non-NS procedure. Erectile function was assessed by the abridged five-item version of the International Index of Erectile Function questionnaire, referred to as the Sexual Health Inventory for Men (SHIM), at baseline and 1 year afterSildenafil Citrate (Viagra) use. The patients' charts were retrospectively reviewed to find factors associated with a successful outcome, which was defined as successful vaginal intercourse. Association with success was assessed by chi-square analysis and the Cochran Armitage test for trend. Bonferroni correction for multiple comparisons was used, with an overall significance level of 0.05 for each factor assessed. RESULTS: The mean age was 60.1 +/- 6.25 years, and the mean interval from RP to drug use was 3 months. After treatment with sildenafil, 100 (57%) of 174 patients responded to the drug: 79 (76%) of 104 in the bilateral NS group, 15 (53.5%) of 28 in the unilateral NS group, and 6 (14.2%) of 42 in the non-NS group. SHIM analysis showed that the magnitude of the improvement was greater in the bilateral NS group (19.97 +/- 1.12) than in the unilateral NS (15.89 +/- 3.38) or non-NS (10.06 +/- 2.0) groups (P <0.020). Four factors were significantly associated statistically with a successful outcome: the presence of at least one neurovascular bundle, a preoperative SHIM score of 15 or greater, age 65 years old or younger, and interval from RP to drug use of more than 6 months (P <0.001). CONCLUSIONS: The efficacy of Sildenafil Citrate (Viagra) after RP correlated with the degree of neurovascular bundle preservation, preoperative erectile function status, age, and interval before starting treatment

Efficacy and safety of oralSildenafil Citrate (Viagra) in men with Erectile Dysfunction and spinal cord injury.

OBJECTIVE: To assess the efficacy ofSildenafil Citrate (Viagra) in men with spinal cord injury (SCI) and Erectile Dysfunction (ED). METHODS: Seventeen men with SCI were selected from February to September 1998 forSildenafil Citrate (Viagra) treatment of ED. The initial dose of 25 mg was increased by 25-mg increments as needed. Patients underwent baseline physical examination and answered questions from the abridged International Index of Erectile Function before and during therapy. RESULTS: Sixteen patients tolerated therapy; 1 developed hypotension and discontinued therapy. There was significant improvement in erectile function (P < .05) after 5.3 +/- 2.2 months when compared with baseline or previous therapies (P < .05). Of the 17 patients, 94% recommendedSildenafil Citrate (Viagra) to others. Six of these 16 patients were available for long-term follow-up. There was further significant improvement in quality of erection (P < .05), but no change in satisfaction. CONCLUSION:Sildenafil Citrate (Viagra) is effective and well tolerated in men with SCI and ED

Atorvastatin enhances sildenafil-induced vasodilation through nitric oxide-mediated mechanisms.

Statins have cholesterol-independent effects including an increased vascular nitric oxide (NO) activity and are commonly used by patients with cardiovascular disease. Such patients frequently have Erectile Dysfunction, which may be treated with sildenafil, a selective inhibitor of phosphodiesterase type 5. Since statins andSildenafil Citrate (Viagra) can activate the NO-cGMP pathway, we investigated whether pre-treatment with atorvastatin (0, 5 and 30 mg/kg/day) for 2 weeks affectsSildenafil Citrate (Viagra) (1 pM-100 mM)-induced relaxation of aortic rings isolated from Wistar rats. We also examined the hemodynamic consequences of this interaction in Wistar rats. Plasma nitrite/nitrate (NOx) concentrations were determined using an ozone-based chemiluminescence assay. While pre-treatment with atorvastatin increased the potency of sildenafil-induced vasorelaxation (P<0.01), no differences were observed in the maximum sildenafil-induced relaxation. Pre-incubation of aortic rings with NG-nitro-L-arginine methyl ester (L-NAME) reversed atorvastatin-induced increase in the potency ofSildenafil Citrate (Viagra) relaxation. In addition, pre-treatment with atorvastatin enhanced plasma NOx concentrations and sildenafil-induced hypotension and tachycardia (all P<0.05). These results suggest that atorvastatin increases the vascular sensitivity toSildenafil Citrate (Viagra) through NO-mediated mechanisms

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