Sympathetic hypoactivity leads to hypocontractility of the corpus cavernosum in sickle cell mice: a mechanism contributing to priapism.

Priapism, a prevalent complication in sickle cell disease (SCD) patients, manifests as prolonged and painful erections unrelated to sexual arousal. The detailed mechanisms contributing to this condition, especially regarding sympathetic function in the corpus cavernosum that maintains penile flaccidity, remain to be elucidated. In this study, it was hypothesized that the pathways of the sympathetic nervous system would be down-regulated, thereby contributing to the development of ischemic priapism in sickle cell disease.

Impact of intravascular hemolysis on functional and molecular alterations in the urinary bladder: implications for an overactive bladder in sickle cell disease.

Patients with sickle cell disease (SCD) display an overactive bladder (OAB). Intravascular hemolysis in SCD is associated with various severe SCD complications. However, no experimental studies have evaluated the effect of intravascular hemolysis on bladder function.

Soluble guanylate cyclase stimulators and activators: new horizons in the treatment of priapism associated with sickle cell disease.

Priapism, defined as a prolonged and often painful penile erection occurring without sexual stimulation or desire, is a common complication in sickle cell disease (SCD), affecting up to 48% of male patients. This condition presents significant clinical challenges and can lead to erectile dysfunction if not properly managed. Current pharmacological treatments for SCD-related priapism are primarily reactive rather than preventative, highlighting a gap in effective medical intervention strategies.

The role of autophagy in prostate cancer and prostatic diseases: a new therapeutic strategy.

Background: Autophagy is a well-conserved catabolic process that plays a key role in cell homeostasis. In the prostate, defective autophagy has been implicated in the genesis and progression of several pathological conditions.

Aim: The present review explored the autophagy pathway in prostate-related dysfunctions, focusing on prostate cancer (PCa), benign prostatic hyperplasia (BPH) and prostatitis.

Nitric Oxide Resistance in Priapism Associated with Sickle Cell Disease: Mechanisms, Therapeutic Challenges, and Future Directions.

Patients with sickle cell disease (SCD) display priapism, a prolonged penile erection in the absence of sexual arousal. The current pharmacological treatments for SCD-associated priapism are limited and focused on acute interventions rather than prevention. Thus, there is an urgent need for new drug targets and preventive pharmacological therapies for this condition.

Hydroxyurea does not reverse functional alterations of the nitric oxide-cGMP pathway associated with priapism phenotype in corpus cavernosum from sickle cell mouse.

Sickle cell disease (SCD) is a genetic disorder that has been associated with priapism. The role of hydroxyurea, a common SCD therapy, in influencing the nitric oxide (NO)-cGMP pathway and its effect on priapism is unclear. To investigate the effect of hydroxyurea treatment on smooth muscle relaxation of corpus cavernosum induced by stimulation of the NO-cGMP pathway in SCD transgenic mice and endothelial NO synthase gene-deficient (eNOS-/-) mice, which are used as model of priapism associated with the low bioavailability of endothelial NO.

Haptoglobin treatment contributes to regulating nitric oxide signal and reduces oxidative stress in the penis: A preventive treatment for priapism in sickle cell disease.

In sickle cell disease (SCD), reduced bioavailability of endothelial NO and cGMP results in reduced expression of phosphodiesterase type 5 (PDE5), thus impairing the penile erection control mechanism and resulting in prolonged penile erection (priapism). In SCD, reduced NO bioavailability is associated with excess plasma hemoglobin due to intravascular hemolysis and increased oxidative stress. Haptoglobin is the plasma protein responsible for reducing plasma hemoglobin levels, but in SCD, haptoglobin levels are reduced, which favors the accumulation of hemoglobin in plasma.

Intravascular hemolysis leads to exaggerated corpus cavernosum relaxation: Implication for priapism in sickle cell disease.

Patients with sickle cell disease (SCD) display priapism. Clinical studies have shown a strong positive correlation between priapism and high levels of intravascular hemolysis in men with SCD. However, there are no experimental studies that show that intravascular hemolysis promotes alterations in erectile function.

Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse.

Background: Children and adult with sickle cell disease (SCD) display priapism associated with low nitric oxide (NO) bioavailability and oxidative stress in penis.

Aim: This study aimed to evaluate the effects of hybrid compound RVT-FxMe, derived from resveratrol bearing a NO-donor subunit, on two murine model that display priapism phenotype, SCD transgenic mice and endothelial NO synthase gene-deficient (eNOS-/-) mice.

Methods: Wild-type, SCD, and eNOS-/- mice were treated with RVT-FxMe (25 mg/kg/d, 2 weeks).

Lipopolysaccharide reduces urethral smooth muscle contractility via cyclooxygenase activation.

Lipopolysaccharide (LPS) is a component of gram-negative bacteria wall that elicits inflammatory response in the host through the toll-like receptor 4 (TLR4) activation. In the lower urinary tract (LUT), bacteria-derived LPS has been associated with lower urinary tract symptoms (LUTS); however, little is known about the effects of LPS in the urethral smooth muscle (USM). In the present study, we evaluated the functional and molecular effects of LPS in mouse USM in vitro, focusing on the LPS-induced TLR4-signaling pathway.

Preserved activity of soluble guanylate cyclase (sGC) in iliac artery from middle-aged rats: Role of sGC modulators.

Vascular aging leads to structural and functional changes. Iliac arteries (IA) provide blood flow to lower urinary tract and pelvic ischemia has been reported as an important factor for bladder remodeling and overactivity. Dysfunction of the nitric oxide (NO)-cyclic guanosine monophosphate pathway (cGMP) is one factor involved in the development of lower urinary tract (LUT) disorders.

Toll-like receptor 9 regulates metabolic profile and contributes to obesity-induced benign prostatic hyperplasia in mice.

Background: Benign prostatic hyperplasia (BPH) is associated with obesity and prostatic inflammation. The present study investigated the participation of toll-like receptor 9 (TLR9) in obesity-induced BPH, focusing on metabolic impairments, damage-associated molecular patterns (DAMP) levels and prostatic oxidative stress generation.

Methods: C57BL/6 (WT) and TLR9 mutant male mice were fed with regular or high-fat diet for 12 weeks.

Reconstitution of autophagy ameliorates vascular function and arterial stiffening in spontaneously hypertensive rats.

Insufficient autophagy has been proposed as a mechanism of cellular aging, as this leads to the accumulation of dysfunctional macromolecules and organelles. Premature vascular aging occurs in hypertension. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated in clinical and experimental hypertension.

Impact of Immune System Activation and Vascular Impairment on Male and Female Sexual Dysfunction.

Introduction: Male and female sexual dysfunction (SD) is considered a multifactorial condition. Numerous studies have shown the involvement of inflammatory processes in this pathological condition. Sexual intercourse requires healthy and functioning vessels to supply the pelvic region in both males and females, generating penile erection and clitoral and vaginal lubrication, respectively.

Formyl peptide receptor-1 activation exerts a critical role for the dynamic plasticity of arteries via actin polymerization.

Several human diseases, include cancer and stroke are characterized by changes in immune system activation and vascular contractility. However, the mechanistic foundation of a vascular immuno-physiology network is still largely unknown. Formyl peptide receptor-1 (FPR-1), which plays a vital role in the function of the innate immune system, is widely expressed in arteries, but its role in vascular plasticity is unclear.

Inhibition of Multidrug Resistance Proteins by MK 571 Enhances Bladder, Prostate, and Urethra Relaxation through cAMP or cGMP Accumulation.

The biologic effect of cAMP and cGMP is terminated by phosphodiesterases and multidrug resistance proteins MRP4 and MRP5, which pump cyclic nucleotides out of the cell. Therefore, this study aimed to characterize the role of MRP inhibitor, MK 571 (3-[[[3-[(1)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl][[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propanoic acid), in the bladder, prostate, and urethra of male mice by means of functional assays, protein expression, and cyclic nucleotide quantification. The cumulative addition of MK 571 (1-30 M) produced only small relaxation responses (approximately 25%) in all studied tissues.

Influence of the periprostatic adipose tissue in obesity-associated mouse urethral dysfunction and oxidative stress: Effect of resveratrol treatment.

Obese mice display overactive bladder (OAB) associated with impaired urethra smooth muscle (USM) function. In this study, we evaluated the role of the adipose tissue surrounding the urethra and prostate in obese mice (here referred as periprostatic adipose tissue; PPAT) to the USM dysfunction. Male C57BL6/JUnib mice fed with either a standard-chow or high-fat diet to induce obesity were used.

Hypertension Induced Morphological and Physiological Changes in Cells of the Arterial Wall.

Morphological and physiological changes in the vasculature have been described in the evolution and maintenance of hypertension. Hypertension-induced vascular dysfunction may present itself as a contributing, or consequential factor, to vascular remodeling caused by chronically elevated systemic arterial blood pressure. Changes in all vessel layers, from the endothelium to the perivascular adipose tissue (PVAT), have been described.

Deletion or pharmacological blockade of TLR4 confers protection against cyclophosphamide-induced mouse cystitis.

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic inflammatory disease without consistently effective treatment. We investigate the role of toll-like receptor 4 (TLR4) on voiding dysfunction and inflammation in the cyclophosphamide (CYP)-induced mouse cystitis. Male C57BL/6 [wild-type, (WT)] and/or TLR4 knockout (TLR4) mice were treated with an injection of CYP (300 mg/kg, 24 h) or saline (10 ml/kg).

Micturition dysfunction in four-month old ovariectomized rats: Effects of testosterone replacement.

Aims: Androgen deficiency has been implicated in urological complications of postmenopausal women. This study examined the effects of testosterone replacements on the lower urinary tract dysfunction in 4-month old ovariectomized (OVX) rats.

Main Methods: Sprague-Dawley female rats were OVX bilaterally.

How important is the α-adrenoceptor in primate and rodent proximal urethra? Sex differences in the contribution of α-adrenoceptor to urethral contractility.

Urethral smooth muscle (USM) contributes to urinary continence by contracting during the urine storage phase, which is mainly mediated by activation of postjunctional α-adrenoceptors. Males and females show differences in the functioning of the lower urinary tract and the most common urinary tract symptoms (LUTS). LUTS in men typically occur in association with bladder outlet obstruction, whereas in women urinary urge-incontinence symptoms are more common.

Sympathetic Hyperactivity, Increased Tyrosine Hydroxylase and Exaggerated Corpus Cavernosum Relaxations Associated with Oxidative Stress Plays a Major Role in the Penis Dysfunction in Townes Sickle Cell Mouse.

Background: Sickle cell disease patients display priapism that may progress to erectile dysfunction. However, little is known about the pathophysiological alterations of corpus cavernosum in sickle cell disease.

Objective: Thus, this study aimed to evaluate the functional and molecular alterations of sympathetic machinery and nitric oxide-cyclic guanosine monophosphate signaling pathway in Townes transgenic sickle cell disease mice.