Intracavernosal OnabotulinumtoxinA Exerts a Synergistic Pro-Erectile Effect When Combined With Sildenafil in Spontaneously Hypertensive Rats.

Background: Botulinum toxin A (BTX-A) has a variety of uses in medicine. Some evidence suggests that intracavernosal (ic) BTX-A injection administered in addition to phosphodiesterase type 5 inhibitors (PDE5-Is) could effectively treat erectile dysfunction (ED) in insufficient responders to PDE5-Is.

Aim: To provide experimental pharmacological evidence for the use of onabotulinumtoxinA ic alone or in combination with PDE5-Is for difficult-to-treat ED.

Enteric Nervous System Remodeling in a Rat Model of Spinal Cord Injury: A Pilot Study.

The physiopathology of digestive disorders in patients with spinal cord injury (SCI) remains largely unknown, particularly the involvement of the enteric nervous system (ENS). We aimed in a rat model of chronic thoracic SCI to characterize (1) changes in the neurochemical coding of enteric neurons and their putative consequences upon neuromuscular response, and (2) the inflammatory response of the colon. motility of proximal and distal colon segments of SCI and control (CT) rats were studied in an organ chamber in response to electrical field stimulation (EFS) and bethanechol.

Silodosin improves functional consequences of lower urinary tract obstruction secondary to benign prostate hypertrophy, a proof of concept study in the spontaneously hypertensive rat supplemented with testosterone.

Background: The main purpose of this study is to investigate the effect of silodosin on the urodynamic consequences in a previously established model of lower urinary tract symptoms associated with benign prostate hyperplasia, the spontaneously hypertensive rats (SHR) supplemented with testosterone.

Methods: Three groups of animals (8-week-old; n = 10/group) were considered: Wistar Kyoto (control) rats (WKY), SHR supplemented with testosterone at 3 mg/kg/day and treated with either vehicle (SHR-T, n = 10) or silodosin at 0.1 mg/kg/day (SHR-T + silodosin, n = 10) by oral gavage for 6 weeks.

European Society for Sexual Medicine Consensus Statement on the Use of the Cavernous Nerve Injury Rodent Model to Study Postradical Prostatectomy Erectile Dysfunction.

Introduction: Rodent animal models are currently the most used in vivo model in translational studies looking into the pathophysiology of erectile dysfunction after nerve-sparing radical prostatectomy.

Aim: This European Society for Sexual Medicine (ESSM) statement aims to guide scientists toward utilization of the rodent model in an appropriate, timely, and proficient fashion.

Methods: MEDLINE and EMBASE databases were searched for basic science studies, using a rodent animal model, looking into the consequence of pelvic nerve injury on erectile function.

Extracorporeal Shock Waves Therapy Delivered by Aries Improves Erectile Dysfunction in Spontaneously Hypertensive Rats Through Penile Tissue Remodeling and Neovascularization.

Background: Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been reported to improve erectile function in patients with moderate-to-severe erectile dysfunction (ED) or even convert phosphodiesterase type 5 inhibitors nonresponders to responders. ED is highly prevalent in hypertensive patients. The effect of Li-ESWT on an animal model of hypertension-associated ED has not been reported.

The Favorable Effect of Empagliflozin on Erectile Function in an Experimental Model of Type 2 Diabetes.

Introduction: Following the results of the EMPA-REG Outcome trial, we hypothesized that empagliflozin, a highly potent and specific sodium/glucose cotransporteur 2 inhibitor, could improve type 2 diabetes mellitus (T2DM)-associated erectile dysfunction (ED), a highly prevalent complication of T2DM, very often coexisting with cardiovascular complications and considered as a prognostic factor of cardiovascular disease in men with diabetes.

Aim: To investigate the effects of chronic treatment with empagliflozin on ED in a T2DM rat model in the presence or absence of sildenafil.

Methods: Male Goto-Kakizaki (GK), a model of T2DM, and age-matched Wistar rats received placebo or empagliflozin treatment at 25.

Low Intensity Extracorporeal Shock Wave Therapy Improves Erectile Function in a Model of Type II Diabetes Independently of NO/cGMP Pathway.

Purpose: Erectile dysfunction is highly prevalent in type II diabetes mellitus. Low intensity extracorporeal shock wave therapy improves erectile function in patients with erectile dysfunction of vasculogenic origin, including diabetes. However, its mode of action remains unknown.

Does Reduction of Number of Intradetrusor Injection Sites of aboBoNTA (Dysport®) Impact Efficacy and Safety in a Rat Model of Neurogenic Detrusor Overactivity?

Intradetrusor injections of Botulinum toxin A-currently onabotulinumtoxinA-is registered as a second-line treatment to treat neurogenic detrusor overactivity (NDO). The common clinical practice is 30 × 1 mL injections in the detrusor; however, protocols remain variable and standardization is warranted. The effect of reducing the number of injection sites of Dysport(®) abobotulinumtoxinA (aboBoNTA) was assessed in the spinal cord-injured rat (SCI).

Evaluation of the effects of a new intravaginal gel, containing purified bovine colostrum, on vaginal blood flow and vaginal atrophy in ovariectomized rat.

Introduction: Vaginal dryness due to vaginal atrophy is a common complaint of postmenopausal women, interfering with sexual function and quality of life. Hormone replacement therapy is the only effective therapy but with known risks that leave unmet medical needs. A new product, ZP-025 vaginal gel, containing purified (dialyzed lyophilized) bovine colostrum, has been developed for the treatment of vaginal dryness secondary to vaginal atrophy.

Bladder and erectile dysfunctions in the Type 2 diabetic Goto-Kakizaki rat.

Despite the fact that urogenito-sexual complications significantly impact the quality of life of diabetic patients, a robust in vivo experimental model is lacking. Bladder and erectile function in the Type 2 diabetic Goto-Kakizaki (GK) rat and responses to standard-of-care treatments for each disorder have been assessed. GK rats (n = 25, 18-wk-old, GK/Par colony) and age-matched Wistar rats (n = 23), characterized for their metabolic parameters, were used.

Involvement of connexins 43 and 45 in functional mechanism of human detrusor overactivity in neurogenic bladder.

Objective: To assess the involvement of connexins (Cxs) 43 and 45 in the selective inhibition of detrusor contractions in patients with neurogenic detrusor overactivity (NDO).

Materials And Methods: Detrusor strips with and without mucosa were obtained from patients undergoing cystectomy for either neurogenic bladder with NDO refractory to pharmacologic treatment or bladder cancer with no overactive bladder symptoms (ie, control group). The strips were isometrically mounted in organ baths.

A new experimental rat model of erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: the testosterone-supplemented spontaneously hypertensive rat.

Unlabelled: What's known on the subject? and What does the study add? Lower urinary tract symptoms (LUTS) resulting from benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are common problems in the aging male population. Moreover, several recent studies have shown that ED is closely associated with the presence and severity of LUTS independently of co-morbidities. However, the pathophysiological mechanisms linking LUTS/BPH and ED remain largely unexplored.

An aryloxypropanolamine hβ3-adrenoceptor agonist as bladder smooth muscle relaxant.

The relaxant effect of an aryloxypropanolamine β3-adrenoceptor agonist on carbachol pre-contracted human detrusor muscle strips was evaluated and compared with literature results from reference compounds of similar mode of action, including mirabegron. A significant relaxation was observed for rac-4-{2-hydroxy-3-[1-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-4-ylamino]propoxy}-2-(hydroxymethyl)phenol which was similar to that exerted by mirabegron. In order to allow for a thorough discussion of results in comparison to reference compounds, their affinity, selectivity and efficacy as hβ3-AR agonists have been evaluated and discussed thoroughly.

Minimal effective dose of dysport and botox in a rat model of neurogenic detrusor overactivity.

Background: Two botulinum toxins A have been evaluated for the treatment of refractory neurogenic detrusor overactivity (NDO) in humans: Dysport (abobotulinumtoxinA) and Botox (onabotulinumtoxinA). However, these two distinct commercialized products have different potency units and are not interchangeable.

Objective: Assessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord-injured (SCI) rats with NDO.

Combination of BAY 60-4552 and vardenafil exerts proerectile facilitator effects in rats with cavernous nerve injury: a proof of concept study for the treatment of phosphodiesterase type 5 inhibitor failure.

Background: Radical prostatectomy (RP) is frequently responsible for erectile dysfunction (ED). Post-RP patients often show a failure to respond to phosphodiesterase type 5 (PDE5) inhibitors.

Objective: The acute effect of BAY 60-4552, the soluble guanylate cyclase (sGC) stimulator, and vardenafil were evaluated alone or in combination on erectile responses to electrical stimulation of the cavernous nerve (ES CN) in rats with cavernous nerve (CN) crush injury-induced ED.

Effects of potassium channel modulators on myogenic spontaneous phasic contractile activity in human detrusor from neurogenic patients.

Objective: To characterize the spontaneous contractile activity (SCA) developed by detrusor from patients with neurogenic detrusor overactivity (NDO) because the alteration of detrusor properties plays a critical role in the pathogenesis of detrusor overactivity, as well as to evaluate the role of K(ATP) and K(Ca) channels on this SCA because these channels regulate detrusor SCA in many species, including humans without overactive bladder (OAB).

Patients And Methods: Human bladder samples were obtained from 44 patients undergoing cystectomy for bladder cancer with no known OAB symptoms and from 38 patients suffering from urodynamically diagnosed NDO. Detrusor strips with or without urothelium/suburothelium were mounted isometrically in organ baths filled with Krebs-HEPES (37 °C; 95% O(2) /5% CO(2) ).

Vardenafil decreases bladder afferent nerve activity in unanesthetized, decerebrate, spinal cord-injured rats.

Background: Phosphodiesterase type 5 inhibitors (PDE5-Is) improve storage symptoms in benign prostatic hyperplasia patients, despite a lack of effect on peak urinary flow rate. Moreover, vardenafil improves urodynamic parameters in spinal cord-injured (SCI) patients with neurogenic detrusor overactivity (NDO). SCI rats also display NDO characterized by nonvoiding contractions (NVCs) during bladder filling, resulting in an increased bladder afferent nerve firing (BANF).

Nitric oxide/cyclic guanosine monophosphate signalling mediates an inhibitory action on sensory pathways of the micturition reflex in the rat.

Background: Overactive bladder can be associated with a hyperexcitability of bladder afferent C-fibres. Several studies have suggested that nitric oxide (NO) or its downstream signalling could modulate the micturition reflex (MR) by reducing the excitability of bladder afferents.

Objectives: To evaluate the role of the NO/cyclic guanosine monophosphate (cGMP) signalling pathway on the MR in a model of bladder hyperactivity (BHA) associated with C-fibre activation in the rat.

How does chronic sildenafil prevent vascular oxidative stress in insulin-resistant rats?

Introduction: Insulin resistance features both endothelial dysfunction and increased oxidative stress. Both disorders are targeted by a chronic treatment with sildenafil. However, the mechanism of action by which chronic sildenafil exerts its effects on reactive oxygen species sources is still largely unknown.

Combination of alfuzosin and tadalafil exerts an additive relaxant effect on human detrusor and prostatic tissues in vitro.

Background: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are highly prevalent in aging men and are strongly linked. Alpha₁-blockers such as alfuzosin are effective monotherapies for LUTS. Phosphodiesterase type 5 (PDE5) inhibitors such as tadalafil are the first-line treatment for ED.

Combination of doxazosin and sildenafil exerts an additive relaxing effect compared with each compound alone on human cavernosal and prostatic tissue.

Introduction: Phosphodiesterase 5 inhibitors (PDE5) such as sildenafil are first-line treatment for erectile dysfunction (ED). Alpha1 (alpha1)-adrenoceptor antagonists such as doxazosin are indicated for the treatment of patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). ED and LUTS/BPH are conditions that are often associated.

Impact of a long-term sildenafil treatment on pressor response in conscious rats with insulin resistance and hypertriglyceridemia.

Background: Insulin resistance constitutes a risk factor for endothelial dysfunction and subsequent cardiovascular diseases including hypertension. Daily treatment with phosphodiesterase type 5 (PDE5) inhibitors has beneficial effects on endothelial function in men with increased cardiovascular risk. Endothelium-dependent vasomotor function is ultimately linked to blood pressure (BP) regulation.