vardenafil-dihydrochloride and Hypertension

Men with erectile dysfunction (ED) are typically older and have one or more underlying cardiovascular conditions.. To determine the efficacy and safety of a new orodispersible tablet (ODT) formulation of vardenafil for the treatment of ED, and whether age, or the presence of underlying conditions affects treatment outcomes.. This is an integrated analysis of data from two phase III, double-blind, multicenter, randomized, parallel-group, placebo-controlled studies that compared 10 mg on-demand vardenafil ODT with placebo in a general population of men with ED, stratified so that approximately 50% of patients were aged ≥ 65 years. Results were reported by age (<6 5 vs. ≥ 65 years) and presence/absence of diabetes, dyslipidemia, or hypertension.. Primary measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile questions 2 (SEP2) and 3 (SEP3).. Of the 701 men randomized (51% aged ≥ 65 years), 686 were included in the intent-to-treat population (placebo, n = 334; vardenafil ODT, n = 352). Vardenafil ODT was significantly superior to placebo for all primary efficacy measures, regardless of age, baseline ED severity, or underlying condition (P < 0.0001 for vardenafil vs. placebo for each endpoint). IIEF-EF scores and SEP2/3 success rates in older patients and men with underlying conditions were not significantly different to those of younger patients or men without underlying conditions. Adverse events (AEs) were mostly mild to moderate in severity, occurring with higher incidence in the vardenafil vs. placebo group. The most frequently reported drug-related AEs in the vardenafil group were headache, flushing, nasal congestion, dizziness, and dyspepsia, consistent with the known safety profile of phosphodiesterase type 5 inhibitors.. Vardenafil ODT significantly improves erectile function in men with ED regardless of age, baseline ED severity, or underlying condition.

Topics: Age Factors; Aged; Biological Availability; Comorbidity; Diabetes Mellitus; Dosage Forms; Double-Blind Method; Dyslipidemias; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Sulfones; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is a very common multidimensional disorder affecting men worldwide. Physical illness, reaction to life stresses, or an unhappy couple relationship influence clinical outcome. Phosphodiesterase type 5 (PDE5) inhibitors are recognized as efficacious and well tolerated, and are the first-line treatment for ED. Sildenafil, tadalafil, and vardenafil are the most widely used and studied PDE5 inhibitors. Data acquired during a routine diagnostic workup for ED should be taken into account when choosing the best PDE5 inhibitor for the individual patient, creating an individualized treatment plan, and going beyond "experience-based" subjective opinion and unfounded ideas and prejudice regarding currently available drugs.. As the process of matching a given patient's profile to any selected PDE5 inhibitor often relies more on physician's personal convictions than on solid evidence, the aim of this review is to identify the main clinical, demographic, and relational factors influencing the choice of the PDE5 inhibitor to be used for the treatment of ED.. A systematic literature search and current treatment guidelines were evaluated in a systematic manner.. The main clinical, cultural, and demographical factors to be considered for the treatment of ED have been identified.. Main factors influencing the choice of the treatment for ED have been described. A short list of items that may help in choosing the right PDE5 inhibitor for the treatment of different patients in daily clinical practice has been prepared.. The simple algorithms prepared should be a useful tool to be used in daily practice, which may help in choosing the right treatment for each subject affected by ED.

Topics: Algorithms; Carbolines; Cardiovascular Diseases; Diabetes Mellitus; Humans; Hypertension; Imidazoles; Impotence, Vasculogenic; Male; Men's Health; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Risk Factors; Sildenafil Citrate; Sulfonamides; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Vardenafil has demonstrated efficacy for the pharmacological management of erectile dysfunction (ED). Accumulating evidence suggests that ED is frequently associated with underlying cardiovascular and metabolic conditions which are thought to be involved in the aetiology of ED. The present review aims to summarise and discuss the available evidence for the efficacy, safety and tolerability of vardenafil in patients with underlying conditions including diabetes, hypertension and dyslipidaemia.. Relevant articles were identified through a PubMed search of clinical trials and postmarketing surveillance studies of vardenafil in patients with ED including those with diabetes, hypertension and dyslipidaemia.. Across all trials, vardenafil showed good efficacy for the treatment of ED in patients with diabetes, hypertension and dyslipidaemia. Vardenafil also showed a favourable safety and tolerability profile. The concomitant use of medication to treat hypertension or dyslipidaemia was not associated with an increase in adverse events following vardenafil treatment.. The prevalence of both diagnosed and undiagnosed underlying conditions is high among men with ED. The evidence presented in this review suggests that vardenafil is efficacious and well tolerated in patients with ED and diabetes, hypertension and/or dyslipidaemia and can be recommended as first-line treatment for ED in patients with these conditions.

Topics: Cardiovascular Diseases; Diabetes Complications; Dyslipidemias; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase (PDE) 5 inhibitors reduce cyclic guanylate monophosphate breakdown, promoting vascular relaxation in the corpora cavernosa and penile erection during sexual stimulation. Sildenafil, vardenafil, and tadalafil were approved as effective treatments for male erectile dysfunction. Because PDE5 is present in artery and vein smooth muscle cells throughout the body, PDE5 inhibitors have mild systemic vasodilatory effects and thus the potential to impact the vascular system. The US Food and Drug Administration has approved PDE5 inhibitors for treating pulmonary hypertension. Moreover, their systemic vasodilating properties theoretically make these drugs suitable for treating hypertension. Studies indicate that PDE5 inhibition may be an option for reducing blood pressure in hypertensive patients. Additional benefits may be related to improved arterial stiffness and endothelial dysfunction, two early vascular abnormalities characterizing essential hypertension. More investigation is needed on PDE5 inhibitors as antihypertensive drugs, especially with slow-release formulations or compounds with long half-life. Studies on safety during long-term administration, interactions with antihypertensive and nonantihypertensive drugs, and effect on target organ damage are needed.

Topics: Antihypertensive Agents; Blood Pressure; Carbolines; Endothelium; Humans; Hypertension; Imidazoles; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

To review the evidence evaluating the efficacy of vardenafil in subgroups of hypertensive patients with erectile dysfunction (ED).. Meta-analysis of randomized, double-blinded, placebo-controlled, flexible-dose vardenafil clinical trials that were >or=12 weeks in duration evaluated men with a >or=6-month history of ED and required a >or=50% failure rate in baseline sexual attempts. The primary endpoints analyzed were the erectile function domain of the International Index of Erectile Function questionnaire (IIEF-EF) and Sexual Encounter Profile questions 2 (SEP2) and 3 (SEP3).. Eight clinical trials were included (n = 2427 patients) consisting of 839 patients (35%) with a self-reported diagnosis of hypertension (HTN): 498 in the vardenafil and 341 in the placebo groups. Vardenafil's efficacy was evidenced by an average increase of 8.9 points in the IIEF-EF (95% CI: 7.4, 10.5) at week 12 compared to placebo, with individual trial values ranging from 16.4 to 26.1 and 11.3 to 17.8 for the vardenafil and placebo groups, respectively. Vardenafil also increased success rates for the ability to obtain erections (SEP2) by 32.4% (95% CI: 27.4%, 37.5%) over a 12-week timeframe compared to placebo, with individual trial values ranging from 57.2% to 92.2% for vardenafil and 32.0% to 66.9% for placebo. Similarly, success rates for the ability to maintain erections (SEP3) improved 38.0% (95% CI: 29.5%, 46.6%) compared to placebo, with individual trial values ranging from 41.7% to 88.2% for vardenafil and 20.5% to 51.4% for placebo. Vardenafil was equally efficacious in improving IIEF-EF, SEP2, and SEP3 in those with and without self-reported HTN.. This meta-analysis demonstrated that vardenafil was significantly more efficacious than placebo for the treatment of ED in patients with comorbid HTN and offered similar treatment benefits in patients without HTN.

Topics: Adult; Aged; Double-Blind Method; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Placebos; Randomized Controlled Trials as Topic; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction occurs commonly in untreated and treated hypertensive patients, impairing adherence to treatment and quality of life. Furthermore, it is a marker for enhanced risk for cardiovascular disease. Phosphodiesterase type 5 (PDE5) inhibitors, sildenafil, vardenafil, and tadalafil, provide effective treatment of erectile dysfunction. They reduce blood pressure in healthy patients: sildenafil 100 mg, -3.7/-3.6 mm Hg; vardenafil 20 mg, -7.5/-8 mm Hg; and tadalafil 20 mg, -1.6/-0.8 mm Hg. Greater declines in blood pressure with a PDE5 inhibitor may be observed in treated and untreated hypertensive patients. The additive effect of PDE5 inhibitors with one or multiple antihypertensive drugs is modest. alpha(1)-Blockers, except tamsulosin, may result in larger declines in blood pressure and cause orthostatic hypotension. Thus, caution should be exercised by using the lowest doses of proportional, variant(1)-blockers and PDE5 inhibitors in combination. Nitrates in combination with PDE5 inhibitors cause a profound decline in blood pressure and are contraindicated.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Antihypertensive Agents; Blood Pressure; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erectile Dysfunction; Humans; Hypertension; Hypotension; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vascular Resistance

Three different phosphodiesterase 5 (PDE5) inhibitors are currently available for the treatment of erectile dysfunction: sildenafil, vardenafil and tadalafil. The differences between these 3 are limited: tadalafil has a long duration of action, while vardenafil has a rapid onset of action after intake. Various studies have suggested that there is an improvement in the partners' sex lives when men use a PDE5 inhibitor for erectile dysfunction. The introduction of PDE5 inhibitors has renewed the interest in PDE inhibitors in general, for example in the treatment of pulmonary hypertension. In the near future PDE inhibitors may be used for various disorders as chronic obstructive pulmonary disease, benign prostatic hyperplasia, hypertension and coronary heart disease.

Topics: Carbolines; Coronary Disease; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Prostatic Hyperplasia; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Risk factors for erectile dysfunction (ED) (hypertension, diabetes, smoking, lipid abnormality) are also risk factors for coronary artery disease. However, most cardiologists do not routinely ask about ED and patients often are reluctant or embarrassed to discuss it. We determined how common ED was in a group of patients with chronic stable coronary artery disease.. We administered the validated Sexual Health Inventory for Men (SHIM) 5-item questionnaire, based on the International Index of Erectile Function questionnaire, to 76 men with chronic stable coronary artery disease during routine outpatient cardiology visits. Most of these men had not previously discussed ED with their cardiologist.. The mean patient age was 64 years (range 40 to 82). The questionnaire took about 5 minutes to complete. Of the patients 47% were on beta blockers, 92% statins, 28% diuretics. SHIM score was 21 or less in 53 men (70%), which is indicative of ED. Of the patients 75% had some difficulty achieving erections (question 2) and 67% had some difficulty maintaining an erection after penetration (question 3). The questionnaire reflected successful sildenafil treatment in 4 patients (SHIM scores 23 to 25). If these 4 men are included as having had ED then 57 of 76 (75%) had ED or recent history of ED.. ED is extremely common in men with chronic coronary artery disease (affecting approximately 75%) yet most cardiologists do not ask about it. The SHIM is a useful, quick and inexpensive tool for discussion and diagnosis of ED in this population. Although it is well established that cardiovascular risk factors are associated with erectile dysfunction, once it is present there is mixed information on whether treating the risk factors will treat the ED. Problems appear to be that lifestyle modification in midlife may simply be too late to effect a change, and some antihypertensive and lipid lowering drugs may actually exacerbate ED. Oral therapy for ED, namely the PDE5 inhibitors, is effective and safe in most cardiac and hypertensive patients. Organic nitrates such as nitroglycerin remain a contraindication to the concomitant use of these drugs. Guidelines for treatment of ED in the cardiac patient issued by the American College of Cardiology/American Heart Association and Princeton Guidelines may be useful in the approach to the cardiac patient with ED.

Topics: Comorbidity; Coronary Disease; Diabetic Angiopathies; Erectile Dysfunction; Heart Diseases; Humans; Hypertension; Imidazoles; Life Style; Male; Penile Erection; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Smoking; Sulfones; Triazines; Vardenafil Dihydrochloride

To evaluate whether the response to on-demand vardenafil could be improved by its daily usage in hypertensive men with erectile dysfunction (ED) who previously did not answer to on-demand regime.. Our main efficacy criterion was per patient percentage of positive answers on the Sexual Encounter Profile question 3 (SEP3). Carotid intima-media thickness (IMT), flow-mediated dilation (FMD), and nitrate-mediated dilation on brachial artery were considered as vascular parameters. A total of 74 hypertensive men with ED aged 50 to 70 years with no major cardiovascular disease were selected from 284 patients initially referred. After vardenafil on-demand usage during 4 weeks, patients with more than 50% of positive answers on the SEP3, or 50% and more than 6 points on the International Index of Erectile Function-Erection Function Domain (IIEF-EF) basal score or positive answer to global evaluation question were considered "responders." "Nonresponders" (n = 35) were randomized to daily vardenafil 10 mg or placebo during 5 weeks along with open 10 mg of vardenafil before intercourse.. In the active group, 38.8% of patients became responders to vardenafil (P < .05). Clinical response to continuous vardenafil correlated with sexual frequency (r = .68, P < .01), Framingham risk score (r = -.65, P < .01), carotid IMT (r = -.61, P = .01) and low-density lipoprotein (LDL)-cholesterol (r = -.64, P < .01).. Daily vardenafil during 5 weeks rescued response to on-demand regime among ED hypertensive men with no major cardiovascular disease. Further clinical trials and cost-effectiveness studies are necessary to confirm these findings.

Topics: Aged; Blood Glucose; Brachial Artery; Carotid Intima-Media Thickness; Cholesterol, LDL; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nitrates; Phosphodiesterase 5 Inhibitors; Piperazines; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase type-5 (PDE-5) inhibitors have previously been evaluated for their efficacy and safety in various clinical trials in men with erectile dysfunction (ED) with or without associated comorbidities.. This is the first prospective, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a PDE-5 inhibitor (i.e., vardenafil) in an exclusive population of men with ED and dyslipidemia.. Three coprimary efficacy measurements (Sexual Encounter Performance [SEP]2, SEP3, International Index of Erectile Function-Erectile Function [IIEF-EF] domain scores) were used to assess the differential effect of vardenafil vs. placebo in this patient population. Adverse events (AEs) safety data were obtained to compare safety outcomes.. This 12-week of randomized, double-blind, placebo-controlled study was conducted in 59 U.S. centers. Patients received either on-demand, flexible-dose vardenafil 10 mg (titrated to 5 mg or 20 mg based upon efficacy and safety) or placebo.. Of the 712 patients screened and entered into the study, 395 were randomized. Baseline demographics for the intent-to-treat population included: mean age, 54.4 years (+/-7.5 standard deviation [SD]); 76% Caucasian; mean body mass index (BMI), 31.7 kg/m(2) (+/-12.7 SD); 47% past/present smoker; and 42% severe ED. Aside from dyslipidemia, other comorbidities included hypertension, 61%; obesity (i.e., BMI >/= 30), 51%; and type 1 or 2 diabetes, 40%. During the 12-week treatment period, the least squares (LS) adjusted mean success rates in patients on vardenafil vs. placebo were: SEP2, 79.09% vs. 51.92%; and SEP3, 66.69% vs. 33.83% (P < 0.001). The LS adjusted mean IIEF-EF domain score for week 12 using LOCF was 21.99 in patients on vardenafil therapy vs. 14.83 in those on placebo (P < 0.001). The most commonly encountered AEs were headache and nasal congestion.. Vardenafil was demonstrated to be safe and effective for managing ED in men with ED and associated dyslipidemia. The results of this study support the role of expanded research on outcomes related to effective ED treatment and aggressive lipid control.

Topics: Coitus; Diabetes Mellitus; Double-Blind Method; Dyslipidemias; Erectile Dysfunction; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Sulfones; Treatment Outcome; Triazines; United States; Vardenafil Dihydrochloride

First-dose success of phosphodiesterase type 5 (PDE5) inhibitors may be adversely affected in patients with comorbidities. This article reports first-dose success rates for vardenafil 10 mg in men with erectile dysfunction (ED) and associated comorbidities who participated in the challenge phase of the Reliability--Vardenafil for Erectile Dysfunction I study. This study involved an open-label, single-dose, 1-week challenge period where patients who achieved SEP-2 (penetration) success were randomised to vardenafil 10 mg or placebo for 12 weeks in a double-blind manner. The first-dose success rates for SEP-2 and SEP-3 (maintenance of erection to completion of intercourse) were stratified according to comorbidities. Safety was assessed using adverse events (AEs). Of 600 men who received a single 10 mg dose of vardenafil, 32% had hypertension, 16% had diabetes and 19% had dyslipidaemia. Vardenafil demonstrated overall effectiveness, including first-dose SEP-2 and SEP-3 success rates in patients with and without specific comorbidities. Initial overall success rates for SEP-2 and SEP-3 during the challenge phase were 87% and 74% respectively. First-dose SEP-2 and SEP-3 success rates were 84% and 66% in men with hypertension (n = 191); 84% and 72% in men with dyslipidaemia (n = 116); and 75% and 58% in men with diabetes (n = 95). Vardenafil was well tolerated and most AEs, including the most frequently reported flushing (3.5%), were mild to moderate in intensity. Vardenafil 10 mg is generally well tolerated and efficacious, providing first-dose success with a consistently high rate of reliability of penetration and maintenance of erection in men with ED and associated comorbidities.

Topics: Adult; Aged; Diabetic Angiopathies; Double-Blind Method; Dyslipidemias; Humans; Hypertension; Imidazoles; Impotence, Vasculogenic; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Vardenafil, a phosphodiesterase type 5 (PDE5) inhibitor, was evaluated in a prospective trial in the primary care setting involving hypertensive men with ED who were receiving at least one antihypertensive medication.. To investigate the safety and efficacy of flexible-dose vardenafil therapy compared with placebo in PDE5 inhibitor-naïve subjects with arterial hypertension and ED.. In this multicenter, randomized, double-blind, placebo-controlled study, 354 patients received placebo or vardenafil (5-20 mg) for 12 weeks. Primary efficacy measures were diary responses to the Sexual Encounter Profile (SEP) questions 2 (vaginal insertion) and 3 (maintenance of erection). Additional efficacy measures included positive responses to the Global Assessment Question (GAQ).. Compared with placebo, vardenafil significantly improved mean SEP2 and SEP3 success rates over the 12-week study period (intention-to-treat [ITT] and last observation carried forward [LOCF]) analysis). For LOCF, SEP2 and SEP3 were 83% for vardenafil vs. 58% for placebo and 67% for vardenafil vs. 35% for placebo, respectively (P<0.0001 vs. placebo). Improved erections (GAQ) were experienced by 80% of vardenafil-treated patients at study end, compared with 40% for placebo (P<0.0001, LOCF). The most commonly reported treatment-emerging adverse events were headache (3.1%) and flushing (1.6%), which were mild-to-moderate and transient in nature. Importantly, there were no significant changes in systolic and diastolic blood pressure or heart rate between the vardenafil and placebo groups. The average number of antihypertensives used per patient was 1.5 and 1.4 in the vardenafil and placebo groups, respectively. Both the incidence of adverse events and the ability to maintain an erection were unaffected by stratification into distinct subsets according to the class of antihypertensive medication being received.. Vardenafil significantly improves EF in hypertensive men treated with concomitant antihypertensive medication, is well tolerated, and does not significantly affect blood pressure.

Topics: Adult; Aged; Antihypertensive Agents; Double-Blind Method; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Risk Factors; Safety; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

We evaluate the correlation between the plasma level of C-reactive protein (CRP) in patients with erectile dysfunction (ED) and hypertension and to set up whether the CRP level affected by the treatment of vardenafil 10 mg orally once daily. A total of 116 male patients with ED and hypertension were enrolled in this prospective study. The patients were divided into two groups, group 1 (ED patients with Not controlled hypertension) and group 2 (ED patients with controlled hypertension). All patients completed the International Index of Erectile Function (IIEF) scores, performed a penile color Doppler ultrasound examination and high sensitivity (hs-CRP) levels. The patients were given vardenafil 10 mg once daily for 3 months and reassessed again. According to the IIEF-EF domain score, there were statistically significant differences between the two groups (P=0.012) with a median value 10.0 (4.0-14.5) and 15.0 (9.0-16.5) between group 1 and group 2, respectively. Regarding to the severe (score<11), moderate (score 11-16) and mild (score 17-25) there were statistically significant differences between the two groups (0.023), (0.001) and (0.001), respectively. The hs-CRP showed statistically significant difference between the two groups (P=0.050) with a median value 2.4 (1.5-3.1) and 1.8 (1.1-2.4) between group 1 and group 2, respectively. The peak systolic velocity (PSV) and end diastolic velocity (EDV) showed statistically significant differences between the two groups (P=0.011) and (P=0.046), respectively. After treatment, there were improvements in the IIEF-EF domain score, severe (score<11), moderate (score 11-16), mild (score 17-25), PSV and EDV in both groups and these improvement were more obvious in (group 2) than (group 1) with a statistically significant differences between the two groups (P<0.05) (except in moderate (score 11-16), no statistically significant difference). The hs-CRP showed statistically significant differences between the two groups after treatment (P=0.049) with a median 2.1 (1.6-2.9) and 1.2 (0.9-2.4) between group 1 and group 2, respectively. Serum hs-CRP was significantly elevated in patients with ED and not controlled hypertension than in ED patients with controlled hypertension. ED patients with controlled blood pressure gave better results with penile duplex than those with not controlled blood pressure. Serum hs-CRP level could be a marker for an endothelial condition in men with ED and hypertension.

Topics: Adult; Aged; C-Reactive Protein; Case-Control Studies; Egypt; Erectile Dysfunction; Humans; Hypertension; Male; Middle Aged; Penile Erection; Prospective Studies; Severity of Illness Index; Vardenafil Dihydrochloride; Vasodilator Agents

In thick ascending limbs (THALs), nitric oxide (NO) decreases NaCl reabsorption via cGMP-mediated inhibition of Na-K-2Cl cotransporter (NKCC2). In angiotensin (ANG II)-induced hypertension, endothelin-1 (ET-1)-induced NO production by THALs is impaired. However, whether this alters NO's natriuretic effects and the mechanisms involved are unknown. In other cell types, ANG II augments phosphodiesterase 5 (PDE5)-mediated cGMP degradation. We hypothesized that NO-mediated inhibition of NKCC2 activity and stimulation of cGMP synthesis are blunted via PDE5 in ANG II-induced hypertension. Sprague-Dawley rats were infused with vehicle or ANG II (200 ng·kg

Topics: Angiotensin II; Animals; Cyclic CMP; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Endothelin-1; Hypertension; Loop of Henle; Male; Nitric Oxide; Nitric Oxide Donors; Phosphodiesterase 5 Inhibitors; Rats; Rats, Sprague-Dawley; Solute Carrier Family 12, Member 1; Vardenafil Dihydrochloride

To investigate whether vasculogenic erectile dysfunction (ED) severity and the clinical response to vardenafil were associated with structural and functional vascular changes in patients with uncomplicated hypertension.. Sexually active hypertensive men (n = 100), aged 50-70 years, completed the International Index of Erectile Function, Erection Function Domain (IIEF-EF) and were divided into 2 groups: 74 men with mild to moderate, moderate, or severe ED (IIEF-EF score ≤18) and without major cardiovascular disease and 26 controls (IIEF-EF score ≥25). Clinical and laboratory evaluations were performed, followed by measurement of the carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) before 4 attempts with 20 mg of vardenafil. The responders had ≥50% positive answers on sexual encounter profile question 3.. The carotid IMT was significantly greater and the FMD was significantly lower in patients with ED than in the control patients. The baseline IIEF-EF score correlated negatively with the carotid IMT (r = -0.48, P < .001) and with the Framingham score (r = -0.41, P < .001) among those with ED. After multivariate logistic regression analysis, the baseline IIEF score was independently and only associated with the carotid IMT (β = 6.105, P = .019). Responders were younger, had a lower cardiovascular risk profile and carotid IMT, and greater baseline IIEF-EF score and FMD than did the nonresponders. On logistic regression analysis, the response to vardenafil was independently associated with the brachial FMD (β = 1.085, P = .002).. In hypertensive men with vasculogenic ED and no other clinical evidence of arteriosclerosis, the ED severity correlated with the carotid IMT, and phosphodiesterase-5 effectiveness correlated with brachial FMD.

Topics: Brachial Artery; Dilatation, Pathologic; Humans; Hypertension; Imidazoles; Impotence, Vasculogenic; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Regional Blood Flow; Severity of Illness Index; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: Brachial Artery; Humans; Hypertension; Imidazoles; Impotence, Vasculogenic; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

The Real-Life Safety and Efficacy of vardenafil study is an international, open-label, prospective, noncomparative, noninterventional study in men with erectile dysfunction (ED).. To determine the safety and efficacy of vardenafil in a large international pool of men with ED (aged ≥ 18 years) and associated underlying conditions (N=73,946), in a real-life setting.. Patients attended an initial physician visit and one to two follow-up visits. Data were acquired by physician interviews and patient diaries and recorded in case report forms (CRFs). Data were pooled from 47 countries in Europe, Asia-Pacific, Latin America, and the rest of the world (excluding the United States and Japan for methodological reasons). Results were stratified by baseline ED severity, body mass index (BMI), and the presence of hypertension, diabetes, lipid metabolism disorder, or cardiovascular disease (CVD).. CRFs and patient questionnaires containing questions on overall improvement of erection, satisfaction with efficacy, and desire to continue vardenafil use.. Many participants had hypertension (32.0%), diabetes (22.1%), lipid metabolism disorder (14.6%), or CVD (42.2%). High percentages of patients reported improvements in erectile function, irrespective of baseline ED severity (mild, 97.0%; moderate, 96.2%; severe, 85.5%), BMI (<25, 94.1%; ≥ 25 and <30, 94.6%; ≥ 30, 92.9%), or the presence of hypertension (93.6%), diabetes (92.6%), lipid metabolism disorder (94.7%), or CVD (93.3%). Over 90% of patients, including those with underlying conditions, reported being "satisfied" or "very satisfied" with vardenafil efficacy, and stated their intention to continue vardenafil use after the end of the study period. The incidence of adverse events was low, and 97.0% of patients were either "satisfied" or "very satisfied" with vardenafil tolerability.. These data from a worldwide population of men with ED and associated underlying conditions show that vardenafil is effective and well-tolerated for the treatment of ED in a real-life setting, supporting its use as a first-line ED therapy.

Topics: Cardiovascular Diseases; Diabetes Mellitus; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Lipid Metabolism Disorders; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase 5 Inhibitors; Piperazines; Product Surveillance, Postmarketing; Prospective Studies; Severity of Illness Index; Sulfones; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase type 5 inhibitors (PDE5i), the most widely used drugs for erectile dysfunction, could also improve lower urinary tract symptoms, essentially due to overactive bladder (OAB), a condition hypothesized to be a result of an increased RhoA/Rho-kinase (ROCK) signaling. Phosphorylation/inactivation of RhoA by cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) activity has been described in vascular smooth muscle.. The aim of this paper was to investigate whether vardenafil-induced cGMP accumulation reduces RhoA/ROCK signaling in bladder.. Spontaneously hypertensive rats (SHRs), a strain genetically prone to develop OAB, were treated with vardenafil (10 mg/kg/day) for 2 weeks. Wistar-Kyoto rats (WKY) were used as control. In vitro experiments were performed in human bladder smooth muscle cells (hBCs).. Urodynamic parameters were registered in vivo in anesthetized WKY and SHRs. RhoA/ROCK activity in bladder was evaluated by molecular and functional studies in tissues and cells.. The intercontraction interval and bladder capacity, and were decreased in SHRs and restored by vardenafil. The in vitro relaxant effect of the ROCK inhibitor Y-27632 was higher in bladder strips from SHR than from WKY and reduced by vardenafil. Nomega-nitro-L-arginine-methyl-ester (a NO-synthase inhibitor, 40 mg/kg/day during the last week of the 2-week treatment with vardenafil) partially antagonized vardenafil effect on Y-27632 responsiveness. Vardenafil prevented RhoA membrane translocation/activation, decreased ROCK activity, and increased cGMP levels in vivo (rat) and in vitro (hBCs). Exposing hBCs to vardenafil increased Ser(188) RhoA phosphorylation, to the same extent as the PDE5-insensitive PKG agonist Sp-8-Br-PET-cGMP. Moreover, vardenafil inhibited several RhoA-dependent functions in hBCs, including smooth muscle gene transcription and endothelin-1-induced migration. These effects were reverted by the PKG inhibitor KT 5823, further suggesting a cGMP/PKG-dependency. In hBCs, vardenafil was active in the low nanomolar range.. This is the first study demonstrating that the effect of vardenafil on OAB could be partially determined by a cGMP-dependent RhoA/ROCK signaling inhibition.

Topics: Animals; Blotting, Western; Cyclic GMP; Hypertension; Imidazoles; Muscle Contraction; Muscle, Smooth; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Rats; Reverse Transcriptase Polymerase Chain Reaction; rho-Associated Kinases; rhoA GTP-Binding Protein; Signal Transduction; Sulfones; Triazines; Urinary Bladder, Overactive; Urodynamics; Vardenafil Dihydrochloride

During the past 18 years, sildenafil has evolved from a potential anti-angina drug to an on-demand treatment for erectile dysfunction and more recently to a new orally active treatment for pulmonary hypertension. Recent studies suggest that the drug has powerful cardioprotective effect against ischemia/reperfusion injury, doxorubicin-induced cardiomyopathy and anti-hypertensive effect induced by chronic inhibition of nitric oxide synthase in animals. Based on several recent basic and clinical studies, it is clear that sildenafil and other clinically approved type-5 phosphodiesterase-5 inhibitors including vardenafil and tadalafil will eventually be developed for several cardiovascular indications including essential hypertension, endothelial dysfunction, ischemia/reperfusion injury, myocardial infarction, ventricular remodeling and heart failure.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Antihypertensive Agents; Carbolines; Cardiomyopathies; Cardiovascular Agents; Cyclic Nucleotide Phosphodiesterases, Type 5; Disease Models, Animal; Doxorubicin; Endothelium, Vascular; Enzyme Inhibitors; Erectile Dysfunction; Heart Failure; Humans; Hypertension; Hypertension, Pulmonary; Imidazoles; Male; Myocardial Infarction; Myocardial Reperfusion Injury; NG-Nitroarginine Methyl Ester; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents; Ventricular Remodeling

The prevalence of erectile dysfunction (ED) is higher in hypertension patients than in non-hypertension men. Because doctors worry about the severe adverse events of drug combination, they tend to be reluctant to prescribe ED medicines for patients. Vardenafil, as a novel and highly selective phosphodiesterase 5 inhibitor, has been proved by many clinical trials to be quite safe for the cardiovascular system. A recent large-scale clinical trial showed that vardenafil could improve erectile function in ED men with hypertension, with sure safety and no significant clinical changes in the index of hypertension or heart rate.

Topics: Adult; Aged; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride