Oral testosterone undecanoate reverses Erectile Dysfunction associated with diabetes mellitus in patients failing on Sildenafil Citrate (Viagra) therapy alone.

AIMS: To evaluate the cause of failure of Sildenafil Citrate (Viagra) to restore erections in patients with organic Erectile Dysfunction (ED) associated with type II diabetes mellitus (DM) and receiving oral antidiabetic drugs. METHODS: Diabetic ED patients (n = 120), aged 43-74 years, failing to respond at least three times to 100 mg Viagra were evaluated. After at least 2 weeks' treatment with oral testosterone undecanoate (Andriol), 100 mg Viagra was used before coitus. ED was assessed with the International Index of Erectile Function (IIEF). Serum total testosterone, prolactin, thyroid stimulating hormone, lipid profile and prostate-specific antigen (PSA) were determined by standard methods and prostate volume by digital rectal examination. Age-matched diabetic ED patients (n = 100) served as controls for baseline values. RESULTS: Viagra non-responders had, at baseline, significantly lower testosterone and more depressed libido than controls. Andriol restored testosterone to normal levels and increased libido. In 84/120 (70%) Viagra non-responders, combined therapy with Andriol induced satisfactory erections, a significant increase in IIEF scale (question (Q) 3 from 2.0 +/- 0.2 to 3.7 +/- 0.3, Q4 from 1.9 +/- 0.1 to 3.4 +/- 0.2, Q12 from 1.0 +/- 0.1 to 4.2 +/- 0.4) and increased sexual contacts from 0.5 to 3-4 per month. No adverse events were noted, and PSA levels remained below 4 ng/ml. CONCLUSION: Decreased testosterone levels in patients with ED and type II DM receiving oral antidiabetic against may be responsible for failure to respond to Sildenafil Citrate (Viagra) therapy. Combination with oral testosterone undecanoate restores sexual function in these patients

Stimulation of the nitric oxide-guanosine 3', 5'-cyclic monophosphate pathway by sildenafil: effect on rectal muscle tone, distensibility, and perception in health and in irritable bowel syndrome.

OBJECTIVES: Nitric oxide, a neurotransmitter in the noncholinergic, nonadrenergic nervous system, is a mediator of relaxation of GI smooth muscle and of visceral nociception mainly studied in vitro.Sildenafil Citrate (Viagra) stimulates the nitric oxide guanosine 3', 5'-cyclic monophosphate (NO-cGMP) pathway through inhibition of phosphodiesterase 5. The aims of this study were to evaluate in vivo the effect of stimulation of the NO-cGMP pathway on rectal tone, distensibility, and perception in healthy individuals and in patients with irritable bowel syndrome (IBS). METHODS: In eight healthy subjects and four patients with IBS rectal tone, distensibility and perception thresholds were measured with an electronic barostat both before and 60 min after administration ofSildenafil Citrate (Viagra) (50 mg p.o.). Perception was scored on a graded scale of 0-6. At the end of a distension series an anatomic questionnaire was filled out by the subjects. RESULTS:Sildenafil Citrate (Viagra) significantly reduced rectal tone in healthy subjects (intrabag volume predrug: 145.5 +/- 18.7 ml vs postdrug: 164.4 +/- 16.9 ml, p = 0.01) and IBS (111.3 +/- 25.2 ml vs 136.5 +/- 33.3 ml; p = 0.01) but did not alter rectal compliance (healthy subjects: 5.8 +/- 0.4 vs 6.3 +/- 0.6 ml/mm Hg, p > 0.05; IBS subjects: 6.1 +/- 0.6 vs 7.1 +/- 1.0 ml/mm Hg, p > 0.05). Intrabag pressure and rectal wall tension to reach perception thresholds for initial sensation, sensation of stool, and urgency were not altered by sildenafil. However, intrabag volumes to reach these thresholds were significantly increased bySildenafil Citrate (Viagra) both in healthy subjects and in patients with IBS. Viscerosomatic referral was unchanged. CONCLUSIONS: Stimulation of the NO-cGMP pathway decreases rectal tone but does not influence rectal distensibility. Relaxation of the rectum is accompanied by an increase in rectal volumes to reach perception thresholds in healthy subjects and in patients with IBS, but no direct effect on rectal perception can be demonstrated

Effects ofSildenafil Citrate (Viagra) on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes.

PURPOSE: Sildenafil, an inhibitor of cGMP-specific phosphodiesterase 5 (PDE5), is currently undergoing evaluation as an oral therapy for penile Erectile Dysfunction. The aims of this study were to investigate the mechanism of action ofSildenafil Citrate (Viagra) on the neurogenic relaxation of human corpus cavernosum (HCC) in vitro and to determine the activity ofSildenafil Citrate (Viagra) against a full range of PDE isozymes. MATERIALS AND METHODS: Strips of HCC tissue were precontracted with phenylephrine. Relaxation responses resulting from electrical field stimulation (EFS) were then determined in the presence and absence of sildenafil. The effects ofSildenafil Citrate (Viagra) on PDE1 to 5 prepared from human tissues and PDE6 from bovine retina were determined by measuring the conversion of [3H]-cGMP or [3H]-cAMP to their respective [3H]-5'-mononucleotides. RESULTS:Sildenafil Citrate (Viagra) (0.001 to 1 microM) enhanced the EFS-induced, nitric oxide (NO) dependent, relaxation of HCC in a concentration-dependent manner to a maximum of 3 times the pretreatment level at 1 microM sildenafil. Compared with zaprinast, an early PDE5 inhibitor,Sildenafil Citrate (Viagra) was approximately 240-fold more potent, inhibiting PDE5 from HCC with a geometric mean IC50 of 3.5 nM. For sildenafil, IC50 values for inhibition of PDE1 to 4 were 80 to more than 8500 times greater than that for PDE5 and the IC50 for PDE6 (33 nM) was approximately 9-fold greater. CONCLUSIONS: The data support the proposal that enhancement of penile erection bySildenafil Citrate (Viagra) in patients with Erectile Dysfunction involves potentiation of the NO-stimulated cGMP signal mediating relaxation of cavernosal smooth muscle during sexual stimulation.Sildenafil Citrate (Viagra) is a potent inhibitor of PDE5 from HCC, with high selectivity for PDE5 relative to other PDE isozymes



Evaluation of the effects of Sildenafil Citrate (Viagra) on canine renal artery, carotid and aortic blood flow with the aid of color Doppler sonography.

INTRODUCTION: Erectile Dysfunction is the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. Oral use of Sildenafil Citrate (Viagra) has been proved to be effective in the treatment of Erectile Dysfunction. Although the effects of Sildenafil Citrate (Viagra) have been investigated in several studies, its effect on aortic, carotid and renal artery blood flow is unknown. The aim of this study was to investigate the early and late phase effects of Sildenafil Citrate (Viagra) on canine aortic, carotid and renal artery blood flow using color Doppler sonography (CDS). MATERIALS AND METHODS: A total of 6 healthy adult dogs was used in this study. With the aid of CDS peak systolic flow rate, end diastolic flow rate, resistivity index (RI) and pulsatility index in aortic, renal and carotid artery were determined before the administration of Sildenafil Citrate (Viagra), 45-75 min after drug administration and after 15 days of drug administration. Data were statistically analyzed using Friedman and Wilcoxon rank tests. p < 0.05 was considered to be statistically significant. RESULTS AND CONCLUSIONS: Significant changes were determined in only 4 out of 28 parameters studied. The significantly changed parameters were as follows: a significant increase in the early and late phase of the postdrug peak of systolic aortic blood flow compared to values before drug administration, an increase in pre- and postdrug RI values of the aorta, a significant decrease in maximum velocity of the right carotid artery, and peak systolic maximum velocity of the left renal segmental artery after drug administration compared to their respective predrug basal values. The results from this study indicate that Sildenafil Citrate (Viagra) has no significant effects on aortic, renal and carotid artery blood flow rate either in the early or in the late phase. Since this study involved only 6 dogs there is a need for further clinical studies involving larger groups of subjects to conclude that this drug is safe with respect to the hemodynamic parameters evaluated in this study.

The female partner's satisfaction with Sildenafil Citrate (Viagra) treatment of Erectile Dysfunction.

BACKGROUND: Data on female partners' satisfaction are scarce, although there have been many articles on patient satisfaction after Sildenafil Citrate (Viagra) treatment. The aim of this study was to evaluate the satisfaction of female partners of patients receiving Sildenafil Citrate (Viagra) for their Erectile Dysfunction (ED) and to assess the female partners' sexual function. METHODS: Ninety-eight patients with ED were treated. Their female partners were asked to answer a questionnaire we have prepared to evaluate the efficacy of treatment, sexual satisfaction and changes in quality of life. It also included a question about female sexual function. From the results, the relationship between their female partner's satisfaction and efficacy of treatment, as well as female sexual function, were assessed. RESULTS: Thirty (31%) questionnaires were returned to us for analysis. Effectiveness of the treatment was acknowledged by 90% of the partners. An improvement in their partner's quality of life was noticed by 60% of the women. The majority (66.7%) of the female partners were satisfied with Sildenafil Citrate (Viagra) treatment and 20% were disappointed. Moreover, 20% of the female partners were concerned about adverse events. Regarding female sexual function, some form of sexual dysfunction affected 46.7% of the women. Furthermore, a significant number (P = 0.0230) of the female partners disappointed with the treatment had some kind of sexual dysfunction. CONCLUSIONS: The results indicated that female partners reported relatively high levels of treatment satisfaction. Female partners' sexual function and anxiety regarding adverse events should be evaluated when their satisfaction with Sildenafil Citrate (Viagra) treatment is poor despite an improvement of erectile function

An in vitro method of studying functional responses of penile resistance arteries under isobaric conditions.

PURPOSE: We developed an in vitro method that allows us to study the physiopharmacological responses of penile resistance arteries under isobaric conditions. MATERIALS AND METHODS: Second to third order penile resistance arteries (internal diameter 170 to 210 microm) were mounted in a pressure myograph and cannulated at each end with small glass cannulas (tip external diameter 150 to 180 microm). Internal diameter was continuously recorded and monitored under an intraluminal pressure of 60 mm Hg. RESULTS: Noradrenaline (0.1 to 0.3 microM) induced a decrease in the luminal diameter of the penile arteries, ie vasoconstriction. This effect was reversed by 1 microM acetylcholine, 1 microM prostaglandin E1 (PGE1) and 1 nM to 1 microM Sildenafil Citrate (Viagra). Furthermore, the vasodilatation induced bySildenafil Citrate (Viagra) was compared by artery internal diameter values under isometric and isobaric conditions. Although the mean potency of this drug +/- SEM, expressed in pD2, was higher in 5 isometric (7.60 +/- 0.04) than in 4 isobaric (7.03 +/- 0.20) preparations (p <0.05), the slope of the curve was lower in 4 isobaric (0.49 +/- 0.02) than in 5 isometric (1.34 +/- 0.11) studies (p <0.01). CONCLUSIONS: Under isobaric conditions all vasoactive agents tested inhibited the noradrenaline induced vasoconstriction. Furthermore, the vasodilatory effect of PGE1 beyond baseline diameter could suggest an inhibitory effect of PGE1 on spontaneous myogenic tone. On the other hand, the effect ofSildenafil Citrate (Viagra) was more potent under isometric than under isobaric conditions. However, the lower slope of the curve under isobaric conditions suggests that the pressure myograph could be a more suitable in vitro model for the study of the activity of penile resistance arteries, and so isobaric conditions correspond more closely to the in vivo situation

Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle.

We tested the hypothesis that sildenafil, singly or in combination with nitric oxide (NO) donors, promotes ventricular tachycardia (VT) and ventricular fibrillation (VF). Vulnerability to VT/VF was tested by rapid pacing in eight isolated normal swine right ventricles (RV). The endocardial activation was optically mapped, and the dynamic action potential duration (APD) restitution curves were constructed with metal microelectrodes. At baseline, no VT/VF could be induced.Sildenafil Citrate (Viagra) (0.2 microg/ml) or NO donor singly or in combination did not alter VT/VF vulnerability. However, when 2 microg/mlSildenafil Citrate (Viagra) was combined with NO donors, the incidence of VT and VF rose significantly (P < 0.01). VT with a single periodic wavefront was induced in five of eight RVs, and VF with multiple wavefronts was induced in all eight RVs. The sildenafil-NO donor pro-VT/VF combination significantly increased the maximum slope of the APD restitution curve and the amplitude of the APD alternans. The pro-VT/VF effects ofSildenafil Citrate (Viagra) were reversible after drug-free Tyrode solution perfusion. We conclude that aSildenafil Citrate (Viagra) (2 microg/ml) and NO donor combination increases VT/VF vulnerability in the normal RV by a mechanism compatible with the restitution hypothesis