Efficacy of vardenafil andSildenafil Citrate (Viagra) in facilitating penile erection in an animal model.

Vardenafil andSildenafil Citrate (Viagra) are potent and specific phosphodiesterase type 5 (PDE 5) inhibitors. In human penile cavernosal smooth muscle cells, we have previously shown that vardenafil has a lower biochemical inhibition constant (Ki) than sildenafil. In this study, we compared the efficacy of vardenafil andSildenafil Citrate (Viagra) in facilitating penile erection in a rabbit model. Penile erections were elicited by submaximal (2.5 or 6 Hz) pelvic nerve stimulation (PNS) repeated every 5 minutes for 30 minutes with or without intravenous (i.v.) administration of vardenafil (1-30 microg/kg) orSildenafil Citrate (Viagra) (10-30 microg/kg). Erectile response was assessed by continuously recording intracavernosal pressure (ICP) and systemic arterial pressure (SAP). All data were expressed as a ratio of ICP:SAP. I.v. administration of either PDE 5 inhibitor facilitated PNS-induced erection and increased ICP:SAP in a dose-dependent manner, reaching peak response at approximately 5 minutes. However, the threshold dose at which facilitation of erection occurred was lower for vardenafil (3 microg/kg) than forSildenafil Citrate (Viagra) (10 microg/kg). At the 10-microg/kg dose (i.v.), the response duration was significantly greater with vardenafil (169 +/- 23 seconds) than withSildenafil Citrate (Viagra) (137 +/- 31 seconds). Direct intracavernosal (i.c.) injection of 1-30 microg/kg vardenafil orSildenafil Citrate (Viagra) also caused dose-dependent increases in ICP:SAP in the absence of PNS. Response durations increased in a dose-dependent manner and lasted more than 5 times that of i.v. drug administration coupled with PNS. Irrespective of the route of administration (i.c. or i.v.), at equivalent doses, vardenafil was significantly more efficacious thanSildenafil Citrate (Viagra) in facilitating pelvic nerve-mediated penile erection and in eliciting erection in the absence of PNS. The increases in ICPs occurred more quickly, were of larger magnitude, and were sustained for longer durations for vardenafil than for sildenafil. On the basis of the biochemical data and physiological responses from this study, further clinical evaluation of vardenafil as treatment for Erectile Dysfunction is warranted

Prehospital consideration of sildenafil-nitrate interactions.

OBJECTIVE: To determine whether paramedics and on-line physicians screen patients for use of Sildenafil Citrate (Viagra) prior to prehospital administration of nitrates. METHODS: A prospective, observational study was performed over a one-month period in three EMS systems. Consecutive radio communications between on-line physicians and paramedics concerning male patients with cardiac complaints were monitored. Investigators observed the frequency with which on-line physicians screened forSildenafil Citrate (Viagra) use prior to ordering nitrates. After observation of the radio communications was completed, a written survey was distributed to all paramedics in the three EMS systems. RESULTS: Seventy-six physician-paramedic interactions were monitored. Nitrates were ordered by on-line physicians in 56 cases. No paramedic reportedSildenafil Citrate (Viagra) use/nonuse, and no on-line physician inquired about the patient's potential use of the drug. Only half of the surveyed paramedics reported that they routinely screen forSildenafil Citrate (Viagra) use, and approximately a fourth reported that its use would not alter their management of chest pain patients. CONCLUSION: In this study, on-line physicians in three EMS settings did not screen forSildenafil Citrate (Viagra) use prior to ordering nitrates. While some paramedics do screen forSildenafil Citrate (Viagra) use, practice patterns among paramedics in these three systems were inconsistent

Comparison of trimetazidine plusSildenafil Citrate (Viagra) to chronic nitrates in the control of myocardial ischemia during sexual activity in patients with coronary artery disease.

A large proportion of patients who have Erectile Dysfunction also have coronary artery disease (CAD). In these patients, nitrate therapy is a contraindication to the use of sildenafil. To assess whether the metabolic anti-ischemic agent, trimetazidine, is effective in controlling episodes of myocardial ischemia during sexual activity in patients who have CAD and use long-term nitrate therapy, we studied 38 men (57 +/- 6 years of age) who had proved CAD. Patients underwent 24-hour ambulatory electrocardiographic monitoring at baseline, after 1 week of oral nitrate therapy (20 mg 3 times a day), and after 1 week of trimetazidine (20 mg 3 times a day). Patients were asked to engage in >/=1 session of sexual intercourse during each session of ambulatory electrocardiographic monitoring. They were instructed to takeSildenafil Citrate (Viagra) (100 mg) 1 hour before sexual intercourse performed at baseline and during therapy with trimetazidine andSildenafil Citrate (Viagra) or placebo (blinded) during therapy with nitrates. A decrease in total ischemic burden was observed with nitrates and trimetazidine compared with baseline (-3 +/- 1.2 episodes/patient/24 hours vs -5 +/- 1.3 episodes/patient/24 hours and -6 +/- 5 min/patient/24 hours vs -8 +/- 3 min/patient/24 hours, p <0.01 for nitrates and trimetazidine vs baseline). Trimetazidine plusSildenafil Citrate (Viagra) was more effective in controlling episodes of myocardial ischemia during sexual activity than nitrates alone (-45 +/- 11% vs -18 +/- 7%, p <0.04). In conclusion, in patients who have CAD, combination therapy withSildenafil Citrate (Viagra) and trimetazidine is more effective than nitrate therapy in the control of ischemic episodes during sexual activity, suggesting that long-term nitrate therapy may be safely switched to trimetazidine therapy when therapy for Erectile Dysfunction is required

Phosphodiesterase inhibition by Sildenafil Citrate (Viagra) attenuates the learning impairment induced by blockade of cholinergic muscarinic receptors in rats.

We examined whether treatment with Sildenafil Citrate (Viagra) (the active compound of Viagra), a cyclic nucleotide phosphodiesterase type 5 inhibitor (PDE5), would reverse the learning impairment induced by cholinergic muscarinic (mACh) receptor blockade [0.75 mg/kg scopolamine HCl, intraperitoneal (i.p.) injections]. Rats were pretrained in a one-way active avoidance of foot shock in a straight runway and the next day received 15 training trials in a 14-unit T-maze. Performance in this maze paradigm requires accurate responding to avoid mild foot shock and has been shown to be sensitive to aging and to impairment in central cholinergic systems. Intraperitoneal (i.p.) injections of scopolamine or saline andSildenafil Citrate (Viagra) or vehicle were given 30 and 15 min before training, respectively. The combined treatment conditions were as follows: saline+vehicle (control), scopolamine (0.75 mg/kg)+vehicle, and scopolamine (0.75 mg/kg)+sildenafil (1.5, 3.0, or 4.5 mg/kg). Behavioral measures of performance included deviations from the correct pathway (errors), run time from start to goal, shock frequency, and duration. Statistical analysis revealed that scopolamine impaired maze performance and thatSildenafil Citrate (Viagra) (3.0 mg/kg) significantly attenuated this impairment in a dose-dependent manner. These results suggest that Sildenafil Citrate (Viagra) may serve as a cognitive enhancer for therapeutic treatment of cholinergic dysfunction in age-related cognitive decline and Alzheimer's dementia (AD)

Histopathologic effect of chronic use of Sildenafil Citrate (Viagra) on the choroid & retina in male rats.

BACKGROUND & OBJECTIVES: Sildenafil Citrate (Viagra) is an oral medication used to treat male impotence by the inhibition of phosphodiesterase-5 in the corpus cavernosum and subsequent facilitation of penile erection. Though the ocular side effects ofSildenafil Citrate (Viagra) have been reported, no information is available on the histopathologic effects of chronic use of Sildenafil Citrate (Viagra) on the ocular vasculature. The present study was undertaken to study the histopathologic effects of chronic use ofSildenafil Citrate (Viagra) on the retina and choroid of male rats. METHODS: Twelve adult male Wistar rats were used in the study. Six of them were given 8 mg/kg/day Sildenafil Citrate (Viagra) orally on alternate days, the other six rats were used as control. The animals were sacrificed after 4 wk of treatment, and the eyes were fixed in 10 per cent formalin solution and sectioned after embedding in paraffin. Sections were cut, stained with haematoxylin-eosin (HE) or periodic acid Schiff (PAS) and examined under light microscope. The choroidal capillary diameter was also measured. RESULTS: The choroidal capillaries were more dilated in the Sildenafil Citrate (Viagra) treated group (mean capillary diameter 3.44 +/- 1.68 microm versus the control of 1.78 +/- 1.36 microm, P < 0.001). The retinal layers and their configuration were unchanged in both the groups. INTERPRETATION & CONCLUSION: Chronic use of Sildenafil Citrate (Viagra) can cause dilatation and congestion in the choroidal vasculature of male rats

Synergistic effects of ANP andSildenafil Citrate (Viagra) on cGMP levels and amelioration of acute hypoxic pulmonary hypertension.

We hypothesized that the phosphodiesterase 5 inhibitor, sildenafil, and the guanosine cyclase stimulator, atrial natriuretic peptide (ANP), would act synergistically to increase cGMP levels and blunt hypoxic pulmonary hypertension in rats, because these compounds act via different mechanisms to increase the intracellular second messenger. Acute hypoxia: Adult Sprague-Dawley rats were gavaged withSildenafil Citrate (Viagra) (1 mg/ kg) or vehicle and exposed to acute hypoxia with and without ANP (10(-8)-10(-5) M ).Sildenafil Citrate (Viagra) decreased systemic blood pressure (103 +/- 10 vs. 87 +/- 6 mm Hg, P < 0.001) and blunted the hypoxia-induced increase in right ventricular systolic pressure (RVSP; percent increase 73.7% +/- 9.4% in sildenafil-treated rats vs. 117.2% +/- 21.1% in vehicle-treated rats, P = 0.03). Also, ANP andSildenafil Citrate (Viagra) had synergistic effects on blunting the hypoxia-induced increase in RVSP (P < 0.001) and on rising plasma cGMP levels (P < 0.05). Chronic hypoxia: Other rats were exposed to prolonged hypoxia (3 weeks, 0.5 atm) after subcutaneous implantation of a sustained-release pellet containing lower (2.5 mg), or higher (25 mg) doses of sildenafil, or placebo. Higher-dose, but not lower-doseSildenafil Citrate (Viagra) blunted the chronic hypoxia-induced increase in RVSP (P = 0.006). RVSP and plasmaSildenafil Citrate (Viagra) levels were inversely correlated in hypoxic rats (r(2) = 0.68, P = 0.044). Lung cGMP levels were increased by both chronic hypoxia and sildenafil, with the greatest increase achieved by the combination. Plasma and right ventricular (RV) cGMP levels were increased by hypoxia, butSildenafil Citrate (Viagra) had no effect. RV hypertrophy and pulmonary artery muscularization were also unaffected by sildenafil. In conclusion,Sildenafil Citrate (Viagra) and ANP have synergistic effects on the blunting of hypoxia-induced pulmonary vasoconstriction. During chronic hypoxia,Sildenafil Citrate (Viagra) normalizes RVSP, but in the doses used,Sildenafil Citrate (Viagra) has no effect on RV hypertrophy or pulmonary vascular remodeling

Are adverse effects ofSildenafil Citrate (Viagra) also caused by inhibition of diamine oxidase?

BACKGROUND: Sildenafil Citrate (Viagra) (Viagra), a drug used to treat Erectile Dysfunctions, causes adverse reactions such as headache, flushing or nasal congestion. Sildanefil's potency as inhibitor of diamine oxidase was investigated, as side effects may also be induced by histamine itself due to an impaired histamine metabolism. METHODS: Placental diamine oxidase inhibition experiments were performed with consecutive dilutions of Sildenafil Citrate (Viagra) (10(-5) to 10(-9) mol/l). In 9 male volunteers in vivo diamine oxidase inhibition was investigated after taking 100 mg Sildenafil Citrate (Viagra). RESULTS: Sildenafil Citrate (Viagra) did not inhibit placental diamine oxidase either in vitro or in vivo. However, infusion of 300 mg of cimetidine inhibited diamine oxidase activity by 27 +/- 7% 15 min after infusion, demonstrating that drugs may inhibit diamine oxidase in vivo. CONCLUSION: As side effects ofSildenafil Citrate (Viagra) are not caused due to inhibition of diamine oxidase, Sildenafil Citrate (Viagra) seems to be harmless for patients suffering from histamine intolerance.

The role ofSildenafil Citrate (Viagra) in the treatment of Erectile Dysfunction in patients with pelvic fracture urethral disruption.

PURPOSE:: Erectile Dysfunction (ED) is a common sequel of pelvic fracture urethral disruption (PFUD). After repair of the urethral injury ED may be the most devastating long-term effect for the patient. Some patients with ED may regain normal erectile function. We prospectively studied the response toSildenafil Citrate (Viagra) and the erectile function of patients with ED due to PFUD. MATERIALS AND METHODS:: The erectile function of patients referred to us with PFUD for urethroplasty were prospectively evaluated before surgery. Patients underwent nocturnal penile tumescence testing and, if results were abnormal, penile duplex ultrasonography with intracavernous injection and arteriography were performed to diagnose the etiology of ED. Patients were questioned about erectile function every 3 months after surgery and if they complained of ED they were offered 100 mg sildenafil. Patients were followed for at least 18 months after surgery. RESULTS:: A total of 29 consecutive patients were evaluated and 22 (76%) of them had ED before surgery. Sufficient followup was available for 15 of the patients. Overall 47% of these patients responded favorably to sildenafil. Of the patients 60% with neurogenic ED and 20% of those with arterial ED responded to this treatment. In 33% of the patients ED resolved within the followup period. All patients with spontaneous resolution of ED previously responded toSildenafil Citrate (Viagra) (71% ofSildenafil Citrate (Viagra) responders). CONCLUSIONS:: In patients with ED due to PFUD, those with neurogenic ED are more likely to respond toSildenafil Citrate (Viagra) than those with arterial damage. Favorable response toSildenafil Citrate (Viagra) may predict spontaneous resumption of normal erectile function over time