Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 26
Filter
1.
Stem Cells Dev ; 33(1-2): 43-53, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37847152

ABSTRACT

As standard therapy for prostate cancer, radical prostatectomy causes cavernous nerve (CN) injury and increases fibrosis and hypoxia-induced penile structural alterations. This study aimed to determine the potential beneficial effects of adipose-derived stem cells (ADSCs) and l-arginine alone or in combination on the penile erection in a rat model of erectile dysfunction caused by bilateral cavernous nerve transection (CNT). Male rats (n = 35) were randomized into five groups: Sham-operated; CNT (4-weeks); CNT plus ADSCs (1 × 106 cells by intracavernosal injection); CNT plus l-arginine (4 weeks, 10 mg/kg/day, oral); and ADSCs combined with l-arginine in CNT. In vivo erectile responses and in vitro relaxant responses were measured. Western blot and immunohistochemistry analyses were used to determine the expression and localization of endothelial nitric oxide synthase, neuronal nitric oxide synthase, transforming growth factor-beta 1, hypoxia-inducible factor-1 alpha (HIF-1α), and apoptosis markers (Bax and Bcl-2). The ratio of smooth muscle to collagen and nerve regeneration were calculated using Masson's trichrome and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. The combined treatment restored diminished erectile responses, endothelium-dependent acetylcholine, and electrical field stimulation-induced relaxation of the corpus cavernosum in rats with CNT, whereas either monotherapy produced only partial improvements. All treatment regimens restored increases in the protein expression of HIF-1 and Bax in rats with CNT. The decrease in smooth muscle mass and NADPH-diaphorase-positive nerve fibers was partially ameliorated by monotherapy, whereas combined therapy led to recovery. These findings indicate that combined treatment with ADSCs and l-arginine may restore erectile function in rats with CNT by inhibiting hypoxia-induced neurotoxicity and preserving endothelium function and smooth muscle content.


Subject(s)
Erectile Dysfunction , Humans , Rats , Male , Animals , Rats, Sprague-Dawley , NADP , bcl-2-Associated X Protein , Erectile Dysfunction/etiology , Erectile Dysfunction/therapy , Penis , Prostatectomy/adverse effects , Stem Cells , Hypoxia , Disease Models, Animal
2.
J Sex Med ; 20(6): 732-741, 2023 05 26.
Article in English | MEDLINE | ID: mdl-37105943

ABSTRACT

BACKGROUND: Sexual dysfunction may indicate severe endocrine diseases. Recent research has suggested a link between hypothyroidism, low testosterone (T) levels, and erectile dysfunction (ED); however, the exact cause is unknown. AIM: We sought to investigate possible beneficial effects of levothyroxine and T alone or in combination on ED in propylthiouracil (PTU)-induced hypothyroid rats. METHODS: Adult Wistar rats (n = 35) were divided into 5 groups: control, PTU-induced hypothyroidism, PTU + levothyroxine, PTU + Sustanon (a mixture of 4 types of T: propionate, phenylpropionate, isocaproate, and decanoate) and PTU + levothyroxine + Sustanon. PTU was given in drinking water for 6 weeks. Four weeks after PTU administration, levothyroxine (20 µg microgram kg/day, oral) and Sustanon (10 mg/kg/week, intramuscular) were given for 2 weeks. Serum levels of total T, triiodothyronine (T3), and thyroxine (T4) were determined. In vivo erectile response and in vitro relaxant responses were measured. Localization of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and phosphodiesterase type 5 (PDE5) were determined using immunohistochemical analysis. The relative area of smooth muscle to collagen was measured using Masson trichrome staining. OUTCOMES: Outcome variables included in vivo erectile function, in vitro relaxant and contractile responses of corpus cavernosum (CC) strips; protein localization of eNOS, nNOS, and PDE5; and smooth muscle content in penile tissue. RESULTS: The rat model of hypothyroidism showed a significant decline in serum levels of total T, T3, and T4. Levothyroxine increased T3 and T4 levels, whereas Sustanon normalized only total T levels. Combined treatment enhanced all hormone levels. Rats with hypothyroidism displayed the lowest erectile response (P < 0.001 vs controls). Combined treatment returned reduced responses, while partial amelioration was observed after levothyroxine and Sustanon treatment alone. Acetylcholine (P < 0.01 vs controls), electrical field stimulation (P < 0.001 vs controls), and sildenafil-induced relaxant responses (P < 0.05 vs controls) were decreased in the CC strips from hypothyroid rats. The combined treatment increased the reduction in relaxation responses. Levothyroxine and Sustanon restored decreases in eNOS and nNOS expression in the hypothyroid group. There was no significant difference in PDE5 expression among groups. Monotreatment partially enhanced reduced smooth muscle mass, while combined therapy completely recovered. CLINICAL IMPLICATIONS: The combination of thyroid hormones and T is likely to be a therapeutic approach for treatment of hypothyroidism-induced ED in men. STRENGTHS AND LIMITATIONS: Beneficial effects of levothyroxine and Sustanon treatment were shown in vitro and in vivo in PTU-induced hypothyroid rats. The main limitation of the study was the lack of measurement of androgen-sensitive organ weights and luteinizing hormone, follicle-stimulating hormone, and prolactin levels. CONCLUSION: These findings demonstrate that neurogenic and endothelium-dependent relaxation responses are reduced by hypothyroidism, which is detrimental to T levels and erectile responses. Levothyroxine and Sustanon combination medication was able to counteract this effect.


Subject(s)
Erectile Dysfunction , Hypothyroidism , Male , Humans , Rats , Animals , Thyroxine/pharmacology , Thyroxine/therapeutic use , Erectile Dysfunction/chemically induced , Erectile Dysfunction/drug therapy , Testosterone/therapeutic use , Propylthiouracil/adverse effects , Rats, Sprague-Dawley , Rats, Wistar , Hypothyroidism/chemically induced , Hypothyroidism/drug therapy , Hypothyroidism/complications
3.
Int. braz. j. urol ; 48(6): 971-980, Nov.-Dec. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1405165

ABSTRACT

ABSTRACT Purpose: This study aimed to assess the possible healing effect of combination treatment with a hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS) plus tadalafil on partial bladder outlet obstruction (PBOO)-induced bladder dysfunction. Materials and Methods: A total of 75 male Sprague-Dawley rats aged 10-wk and 300-350g were divided into five groups; control; PBOO; PBOO+NaHS (5.6mg/kg/day, i.p., 6-wk); PBOO+tadalafil (2mg/kg/day, oral, 6-wk) and PBOO+NaHS+tadalafil. PBOO was created by partial urethral ligation. 6 weeks after obstruction, the in vitro contractile responses of the detrusor muscle and Western blotting, H2S and malondialdehyde assay were performed in bladder tissues. Results: There was an increase in bladder weight(p<0.001) and a decrease in contractile responses to KCl (p<0.001), carbachol (p<0.01), electrical field stimulation (p<0.05) and ATP (p<0.001) in the detrusor smooth muscle of obstructed rats which was normalized after the combination treatment. Cystathionine γ-lyase and cystathionine β-synthase, and nuclear factor kappa B protein levels did not significantly differ among groups. The obstruction induced decrement in 3-mercaptopyruvate sulfur transferase protein expression(p<0.001) and H2S levels(p<0.01) as well as increment in protein expressions of neuronal nitric oxide synthase (NO, p<0.001), endothelial NOS (p<0.05), inducible NOS(p<0.001), hypoxia-inducible factor 1-alpha (p<0.01), and malondialdehyde levels (p<0.01), when combined treatment entirely normalized. Conclusions: Combination therapy has beneficial effects on bladder dysfunction via regulating both H2S and nitric oxide pathways as well as downregulation of oxidative stress and hypoxia. The synergistic effect of H2S and nitric oxide is likely to modulate bladder function, which supports the combined therapy for enhancing clinical outcomes in men with BPH/LUTS.

4.
Int Braz J Urol ; 48(6): 971-980, 2022.
Article in English | MEDLINE | ID: mdl-36173409

ABSTRACT

PURPOSE: This study aimed to assess the possible healing effect of combination treatment with a hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS) plus tadalafil on partial bladder outlet obstruction (PBOO)-induced bladder dysfunction. MATERIALS AND METHODS: A total of 75 male Sprague-Dawley rats aged 10-wk and 300-350g were divided into five groups; control; PBOO; PBOO+NaHS (5.6mg/kg/day, i.p., 6-wk); PBOO+tadalafil (2mg/kg/day, oral, 6-wk) and PBOO+NaHS+tadalafil. PBOO was created by partial urethral ligation. 6 weeks after obstruction, the in vitro contractile responses of the detrusor muscle and Western blotting, H2S and malondialdehyde assay were performed in bladder tissues. RESULTS: There was an increase in bladder weight(p<0.001) and a decrease in contractile responses to KCL(p<0.001), carbachol(p<0.01), electrical field stimulation(p<0.05) and ATP (p<0.001) in the detrusor smooth muscle of obstructed rats which was normalized after the combination treatment. Cystathionine γ-lyase and cystathionine ß-synthase, and nuclear factor kappa B protein levels did not significantly differ among groups. The obstruction induced decrement in 3-mercaptopyruvate sulfur transferase protein expression(p<0.001) and H2S levels(p<0.01) as well as increment in protein expressions of neuronal nitric oxide synthase (NO, p<0.001), endothelial NOS (p<0.05), inducible NOS(p<0.001), hypoxia-inducible factor 1-alpha (p<0.01), and malondialdehyde levels (p<0.01), when combined treatment entirely normalized. CONCLUSIONS: Combination therapy has beneficial effects on bladder dysfunction via regulating both H2S and nitric oxide pathways as well as downregulation of oxidative stress and hypoxia. The synergistic effect of H2S and nitric oxide is likely to modulate bladder function, which supports the combined therapy for enhancing clinical outcomes in men with BPH/LUTS.


Subject(s)
Hydrogen Sulfide , Urinary Bladder Neck Obstruction , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/pharmacology , Adenosine Triphosphate/therapeutic use , Animals , Carbachol/metabolism , Carbachol/pharmacology , Carbachol/therapeutic use , Cystathionine beta-Synthase/metabolism , Cystathionine beta-Synthase/pharmacology , Cystathionine beta-Synthase/therapeutic use , Cystathionine gamma-Lyase/metabolism , Cystathionine gamma-Lyase/pharmacology , Cystathionine gamma-Lyase/therapeutic use , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/pharmacology , Hydrogen Sulfide/therapeutic use , Hypoxia/drug therapy , Hypoxia/metabolism , Hypoxia-Inducible Factor 1/metabolism , Hypoxia-Inducible Factor 1/pharmacology , Hypoxia-Inducible Factor 1/therapeutic use , Male , Malondialdehyde , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type I/metabolism , Oxidative Stress , Rats , Rats, Sprague-Dawley , Sulfides , Sulfur/metabolism , Sulfur/pharmacology , Sulfur/therapeutic use , Tadalafil/pharmacology , Tadalafil/therapeutic use , Transferases/metabolism , Transferases/pharmacology , Transferases/therapeutic use , Urinary Bladder , Urinary Bladder Neck Obstruction/drug therapy
5.
Andrology ; 10(7): 1441-1453, 2022 10.
Article in English | MEDLINE | ID: mdl-35852413

ABSTRACT

BACKGROUND: In different animal models, a histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu) reduced inflammation, oxidative stress and fibrosis which were involved in the pathogenesis of erectile dysfunction (ED), but whether NaBu could improve ED in an experimental animal model of benign prostate hyperplasia (BPH) was not known. OBJECTIVE: To investigate the preventive effect of NaBu on ED in a partial bladder outlet obstruction (PBOO) rat model. MATERIALS AND METHODS: PBOO was induced by partial urethral obstruction. NaBu (20 mg/kg/day) was administered orally to rats for 6 weeks after creation of PBOO. In vivo erectile responses, in vitro relaxation and contraction responses in cavernosal tissue were measured. Real-time polymerase chain reaction (RT-PCR) and Western blot were performed to determine the gene and protein expression. Inflammation, fibrosis, and localization of proteins were evaluated using histological techniques. HDAC activity and tumor necrosis factor (TNF)-α levels were measured in penile tissues. RESULTS: NaBu improved decreased intracavernosal pressure/mean arterial pressure, nitrergic and endothelium-dependent relaxation responses, and contractile responses to phenylephrine and electrical field stimulation in the PBOO group without affecting increased bladder weight. Increased endothelial nitric oxide synthase (eNOS), transforming growth factor (TGF)-ß1, and nuclear factor kappa B (NF-κB) gene levels in PBOO group were ameliorated by NaBu treatment. The administration of NaBu to PBOO rats significantly increased neuronal NOS (nNOS) and decreased TGF-ß1 protein expression. The nuclear/cytosolic ratio of NF-κB demonstrated a decrease in PBOO and all treatment groups compared to control. A significant increase in the nuclear-to-cytoplasmic ratio of nuclear factor erythroid 2-related factor 2 (Nrf2) after PBOO was reduced by the treatment. Both eNOS and inducible NOS (iNOS) protein expression, together with TNF-α levels did not differ in the penile tissue of all groups. In histological analysis, increased TGF-ß1 protein expression and fibrosis, as well as decreased nNOS protein in PBOO, were reversed by the treatment. NaBu did not normalize moderate inflammation in obstructed rats. An increase in the HDAC activity in PBOO was significantly suppressed by NaBu. DISCUSSION: Inhibition of the HDAC activity by NaBu in penile tissue could ameliorate fibrosis-associated changes induced by PBOO. CONCLUSION: NaBu promotes recovery of erectile function, and also significantly prevents penile fibrosis and normalizes TGF-ß1 and nNOS protein expression in a rat model of PBOO. The HDAC pathway may present a promising target to prevent ED in patients with BPH.


Subject(s)
Erectile Dysfunction , Prostatic Hyperplasia , Urinary Bladder Neck Obstruction , Animals , Butyric Acid/metabolism , Butyric Acid/pharmacology , Butyric Acid/therapeutic use , Disease Models, Animal , Erectile Dysfunction/drug therapy , Erectile Dysfunction/etiology , Erectile Dysfunction/metabolism , Fibrosis , Histone Deacetylases/metabolism , Humans , Inflammation/metabolism , Male , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Nitric Oxide Synthase Type III/metabolism , Penis , Phenylephrine/metabolism , Phenylephrine/pharmacology , Prostatic Hyperplasia/pathology , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/pharmacology , Transforming Growth Factors/metabolism , Transforming Growth Factors/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Urinary Bladder Neck Obstruction/complications , Urinary Bladder Neck Obstruction/drug therapy
6.
Drug Discov Today ; 27(10): 103327, 2022 10.
Article in English | MEDLINE | ID: mdl-35905935

ABSTRACT

Throughout 2021, the scientific and medical communities were concentrated on dealing with the acute morbidity and mortality induced by the COVID-19 pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We reviewed the present data for adverse effects of COVID-19 on the different parts of the male urogenital system during the dynamic situation of the COVID-19 pandemic. With the approval of COVID-19 vaccinations, there is a ray of hope at the end of this dark tunnel and a chance to look ahead for the management of long-term consequences in males with urogenital illness. A multidisciplinary investigation of these cases could provide information for establishing and optimizing treatment protocols.


Subject(s)
COVID-19 , Vaccines , Angiotensin-Converting Enzyme 2 , COVID-19/prevention & control , Humans , Male , Pandemics/prevention & control , Peptidyl-Dipeptidase A , SARS-CoV-2 , Urogenital System
7.
Prostate ; 82(12): 1135-1161, 2022 09.
Article in English | MEDLINE | ID: mdl-35579053

ABSTRACT

BACKGROUND: Radical prostatectomy (RP) and radiation treatment are standard options for localized prostate cancer. Even though nerve-sparing techniques have been increasingly utilized in RP, erectile dysfunction (ED) due to neuropraxia remains a frequent complication. Erectile function recovery rates after RP remain unsatisfactory, and many men still suffer despite the availability of various therapies. OBJECTIVE: This systematic review aims to summarize the current treatments for post-RP-ED, assess the underlying pathological mechanisms, and emphasize promising therapeutic strategies based on the evidence from basic research. METHOD: Evaluation and review of articles on the relevant topic published between 2010 and 2021, which are indexed and listed in the PubMed database. RESULTS: Phosphodiesterase type 5 inhibitors, intracavernosal and intraurethral injections, vacuum erection devices, pelvic muscle training, and surgical procedures are utilized for penile rehabilitation. Clinical trials evaluating the efficacy of erectogenic drugs in this setting are conflicting and far from being conclusive. The use of androgen deprivation therapy in certain scenarios after RP further exacerbates the already problematic situation and emphasizes the need for effective treatment strategies. CONCLUSION: This article is a detailed overview focusing on the pathophysiology and mechanism of the nerve injury developed during RP and a compilation of various strategies to induce cavernous nerve regeneration to improve erectile function (EF). These strategies include stem cell therapy, gene therapy, growth factors, low-intensity extracorporeal shockwave therapy, immunophilins, and various pharmacological approaches that have induced improvements in EF in experimental models of cavernous nerve injury. Many of the mentioned strategies can improve EF following RP if transformed into clinically applicable safe, and effective techniques with reproducible outcomes.


Subject(s)
Erectile Dysfunction , Prostatic Neoplasms , Androgen Antagonists/therapeutic use , Erectile Dysfunction/etiology , Erectile Dysfunction/therapy , Humans , Male , Penile Erection/physiology , Prostatectomy/adverse effects , Prostatectomy/methods , Prostatic Neoplasms/pathology
8.
Int J Impot Res ; 34(3): 269-276, 2022 Apr.
Article in English | MEDLINE | ID: mdl-33820978

ABSTRACT

Benign prostatic hyperplasia (BPH) is one of the most prevalent conditions among aged men. The use of 5α-reductase inhibitors (5-ARIs) to treat BPH was linked to erectile dysfunction (ED). Many medicinal plants and secondary metabolites are used in the management of ED. Onion (Allium cepa L.) is an economically affordable vegetable with vital phytochemicals and biological functions. The study aimed to identify the beneficial effects of onion juice on dutasteride (a 5-ARI)-induced ED. Rats were divided into two groups (n = 5 per group): control and dutasteride-treated rats (0.5 mg/kg/day). Dutasteride was administered in drinking water for 12 weeks. Experiments were performed at the end of the 12th week. In vivo erectile responses were measured before and after intracavernosal injection of onion. Relaxant responses to onion juice were examined in the corpus cavernosum (CC). Acetylcholine (ACh)-, electrical field stimulation (EFS)-, sodium nitroprusside (SNP)-induced relaxation responses in CC tissues were evaluated in the absence and presence of onion juice. Total intracavernosal pressure (ICP) and ICP/ mean arterial pressure were significantly reduced in dutasteride-treated rats (1881.14 ± 249.72 mmHg, P < 0.001;0.26 ± 0.03, P < 0.01) as compared to control rats (4542.60 ± 429.19 mmHg, 0.51 ± 0.05), which was normalized after the intracavernous administration of onion (3288.60 ± 185.45 mmHg, 0.58 ± 0.04). Onion markedly induced relaxant responses in control (72.5 ± 4.7) and dutasteride-treated (66.5 ± 2.7) groups after precontraction with phenylephrine. Relaxation responses to onion were partially inhibited after precontraction with KCl (32.5 ± 3.1, P < 0.001). The relaxant responses to ACh (14.9 ± 4.2, P < 0.01) were diminished in dutasteride-treated CC) compared to control CC (59.8 ± 3.4), which was enhanced after the incubation with onion (36.6 ± 4.8). There were no differences in relaxation response to SNP among all groups. However, relaxation response to SNP was reduced in dutasteride-treated CC at 1 µM (P < 0.05) and 10 µM dosages (P < 0.001), which was partially increased after the incubation with onion at 10 µM dosage (P < 0.01). The presence of onion did not change the reduction in EFS-caused relaxation in the dutasteride-treated group. The current data suggest that red onion juice has a restorative effect on erectile function and endothelium-dependent relaxation response following the treatment of dutasteride.


Subject(s)
Erectile Dysfunction , Prostatic Hyperplasia , 5-alpha Reductase Inhibitors/pharmacology , 5-alpha Reductase Inhibitors/therapeutic use , Aftercare , Aged , Animals , Dutasteride/pharmacology , Dutasteride/therapeutic use , Erectile Dysfunction/drug therapy , Erectile Dysfunction/etiology , Humans , Male , Onions , Oxidoreductases/pharmacology , Penis , Prostatic Hyperplasia/complications , Rats , Rats, Sprague-Dawley
9.
J Sex Med ; 18(5): 889-899, 2021 05.
Article in English | MEDLINE | ID: mdl-33785264

ABSTRACT

BACKGROUND: Effects of human umbilical cord blood (HUCB) as a valuable source for stem cell-based therapies have not been studied in persistent post-5-alpha reductase inhibitors (5ARI) erectile dysfunction (PPED). AIM: To determine the effect of intracavernosal injection of HUCB mononuclear cells (MNCs) on ED associated with dutasteride treatment. METHODS: Twenty five adult male Sprague-Dawley rats were divided into 5 groups (n = 5 per group): (i) control, (ii) 8-week dutasteride (0.5 mg/kg/day, in drinking water), (iii) 12-week dutasteride, (iv) 8-week dutasteride+HUCB-MNCs (1 × 106) and (v) 12-week dutasteride+HUCB-MNCs. HUCB-MNCs were administered intracavernosally after eight weeks of dutasteride treatment. Experiments were performed at 4 weeks following the injection of HUCB-MNCs. Erectile responses and isometric tension of corpus cavernosum (CC) were measured. The protein expressions of phosphodiesterase type 5 (PDE5), endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), hypoxia-inducible factor (HIF)-1α and smooth muscle/collagen contents in penile tissue were evaluated by Western blotting, immunohistochemistry, and Masson's trichrome staining, respectively. MAIN OUTCOME: In vivo erectile function, in vitro relaxant and contractile responses of CC, protein expression and localization of PDE5, eNOS, nNOS, HIF-1α, and smooth muscle content in penile tissue. RESULTS: Erectile responses in the dutasteride-treated groups were significantly decreased compared with controls (P < .001), persisting after 4-wk of washout. HUCB-MNCs restored diminished intracavernosal pressure responses, acetylcholine-, sodium nitroprusside-, sildenafil-induced relaxations, and increased phenylephrine and electrical field stimulation (EFS)-induced contractions. Decreased EFS-induced relaxations in dutasteride-treated groups were not restored by HUCB-MNCs. Increased PDE5 and reduced nNOS expressions in dutasteride groups were restored by HUCB-MNCs in the 12-week dutasteride group. eNOS and HIF-1α protein expression and serum total and free testosterone  levels were similar among groups. HUCB-MNCs reversed the decreased smooth muscle/collagen ratio in dutasteride-treated tissues. There was a significant increase in PDE5 and HIF-1α staining in 8-week dutasteride animals. CLINICAL TRANSLATION: This study demonstrates the corrective potential of HUCB-MNCs on some persistent structural and functional deterioration caused by 5ARI treatment in rats, which may encourage further evaluation of HUCB-MNCs in men with PPED. STRENGTHS AND LIMITATIONS: Therapeutic application of intracavernosal HUCB-MNCs is a novel approach for the rat model of post-5ARI ED. Lack of serum and tissue dihydrotestosterone measurements, vehicle injections and characterization of the cells remain limitations of our study. CONCLUSION: The persistent ED after prolonged administration of dutasteride in rats is reversed by HUCB-MNC treatment, which holds promise as a realistic therapeutic modality for this type of ED. Oztekin CV, Yilmaz-Oral D, Kaya-Sezginer E, et al. Beneficial Effects of Human Umbilical Cord Blood Mononuclear Cells on Persistent Erectile Dysfunction After Treatment of 5-Alpha Reductase Inhibitor in Rats. J Sex Med 2021;18:889-899.


Subject(s)
Erectile Dysfunction , 5-alpha Reductase Inhibitors/pharmacology , Animals , Erectile Dysfunction/drug therapy , Fetal Blood , Humans , Male , Penile Erection , Penis , Rats , Rats, Sprague-Dawley
10.
Exp Clin Endocrinol Diabetes ; 129(4): 296-302, 2021 Mar.
Article in English | MEDLINE | ID: mdl-30978726

ABSTRACT

AIM: To investigate the possible beneficial effect of mirabegron [a selective ß3-adrenoceptor (AR) agonist] treatment on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. METHODS: Sprague-Dawley rats (n=20) were divided into two groups: control group and streptozotocin-induced diabetic group. In vivo erectile responses were evaluated after intracavernosal injection of mirabegron (0.4 mg/kg) in rats. The relaxation responses to electrical field stimulation (EFS, 10 Hz), sodium nitroprusside (SNP, 10 nM) and sildenafil (1 µM) of corpus cavernosum (CC) strips were examined after the incubation with mirabegron (10 µM). ß3-ARs expression and localization were determined by Western blot and immunohistochemical analyses in CC tissue. RESULTS: In vivo erectile responses of diabetic rats [intracavernasal pressure (ICP) / mean arterial pressure, 0.17±0.01] were decreased, which were restored after administration of mirabegron (0.75±0.01, P<0.001). The basal ICP (7.1±0.6 mmHg) in diabetic rats was markedly increased after mirabegron (36.1 ±5.4 mmHg, P<0.01). Mirabegron caused markedly relaxation in diabetic rat CC after phenylephrine precontraction. The relaxation responses to EFS and sildenafil were reduced in diabetic CC, which were increased in the presence of mirabegron. Mirabegron enhanced SNP-induced relaxation response in both groups. The expression and immunoreactivity of ß3-ARs localized to CC smooth muscle were observed in control and diabetic rats. CONCLUSIONS: This is the first study to show that intracavernosal administration of mirabegron improved erectile function and neurogenic relaxation of CC in diabetic rats. These results may be supported by further studies using combinations of mirabegron and phosphodiesterase type 5 (PDE5) inhibitors for the treatment of diabetic ED, especially in patients who do not respond to PDE5 inhibitor therapy.


Subject(s)
Acetanilides/pharmacology , Adrenergic beta-3 Receptor Agonists/pharmacology , Diabetes Complications/drug therapy , Diabetes Mellitus, Experimental/complications , Erectile Dysfunction/drug therapy , Thiazoles/pharmacology , Acetanilides/administration & dosage , Adrenergic beta-3 Receptor Agonists/administration & dosage , Animals , Diabetes Complications/etiology , Erectile Dysfunction/etiology , Male , Rats , Rats, Sprague-Dawley , Thiazoles/administration & dosage
11.
Andrology ; 8(6): 1824-1833, 2020 11.
Article in English | MEDLINE | ID: mdl-32672414

ABSTRACT

BACKGROUND: Testosterone (T) deficiency is associated with erectile dysfunction (ED). The relaxant response of T on the corporal smooth muscle through a non-genomic pathway has been reported; however, the in vitro modulating effects of T on human corpus cavernosum (HCC) have not been studied. OBJECTIVES: To compare the effects of various concentrations of T on nitric oxide (NO)-dependent and nitric oxide-independent relaxation in organ bath studies and elucidate its mode of action, specifically targeting the cavernous NO/cyclic guanosine monophosphate (cGMP) pathway. MATERIALS AND METHODS: Human corpus cavernosum (HCC) samples were obtained from men undergoing penile prosthesis implantation (n = 9). After phenylephrine (Phe) precontraction, the effects of various relaxant drugs of HCC strips were performed using organ bath at low (150 ng/dL), eugonadal (400 ng/dL), and hypergonadal (600 ng/dL) T concentrations. The penile tissue measurements of endothelial nitric oxide synthase (eNOS), neuronal (n)NOS, and phosphodiesterase type 5 (PDE5) were evaluated via immunostaining, Western blot, cGMP and nitrite/nitrate (NOx) assays. RESULTS: Relaxation responses to ACh and EFS in isolated HCC strips were significantly increased at all T levels compared with untreated tissues. The sildenafil-induced relaxant response was significantly increased at both eugonadal and hypergonadal T levels. Normal and high levels of T are accompanied by increased eNOS, nNOS, cGMP, and NOx levels, along with reduced PDE5 protein expression. CONCLUSION: This study reveals an important role of short-term and modulatory effects of different concentrations of T in HCC. T positively regulates functional activities, inhibition of PDE5 expression, and formation of cGMP and NOx in HCC. These results demonstrate that T indirectly contributes to HCC relaxation via downstream effects on nNOS, eNOS, and cGMP and by inhibiting PDE5. This action provides a rationale for normalizing T levels in hypogonadal men with ED, especially when PDE5 inhibitors are ineffective. T replacement therapy may improve erectile function by modulating endothelial function in hypogonadal men.


Subject(s)
Cyclic GMP/metabolism , Nitric Oxide/biosynthesis , Penis/metabolism , Testosterone/pharmacology , Cyclic Nucleotide Phosphodiesterases, Type 5/analysis , Erectile Dysfunction/blood , Hormone Replacement Therapy , Humans , Male , Middle Aged , Nitric Oxide/metabolism , Nitric Oxide Synthase Type I/analysis , Nitric Oxide Synthase Type III/analysis , Penile Induration/blood , Sildenafil Citrate/pharmacology , Testosterone/blood
12.
Andrologia ; 52(6): e13606, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32352181

ABSTRACT

Diabetic men are at a higher risk of erectile dysfunction (ED). A tropical plant, clove (Syn. Eugenia caryophyllata, Caryophyllus aromaticus L., Syzygium aromaticum (L.) Merr. & L.M. Perry) from the Myrtaceae family has displayed aphrodisiac activity. The present research aimed to investigate the impacts of clove essential oil (CEO) and the ingredient of CEO, eugenol (E) on ED in diabetic rats. We divided Sprague-Dawley rats into control and diabetic groups. Erectile function was evaluated before and after CEO and E intracavernosal injection. CEO- and E-induced relaxation responses were investigated in isolated corpus cavernosum (CC) using various inhibitors. The intracavernous administration of CEO and E restored erectile responses in diabetic rats. CEO and E induced remarkable relaxation in all groups. CEO- and E-induced relaxation responses were partially inhibited after pre-contraction with KCl. Tetraethylammonium and glibenclamide inhibited the relaxation response to CEO. Glibenclamide inhibited maximum relaxation to E. The inhibitors of nitric oxide synthase (NOS), soluble guanylyl cyclase and nifedipine did not change CEO- and E-induced relaxation responses. The current results suggest that CEO and the major compound of the essential oil, E improved diabetes-induced ED in rats, and CEO caused CC relaxation via K+ channels independently NO signalling pathway.


Subject(s)
Clove Oil/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Erectile Dysfunction/physiopathology , Eugenol/pharmacology , Penile Erection/drug effects , Animals , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Erectile Dysfunction/etiology , Erectile Dysfunction/metabolism , Glyburide/pharmacology , In Vitro Techniques , Injections , Male , Nifedipine/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Oils, Volatile/pharmacology , Penis/drug effects , Potassium Channel Blockers/pharmacology , Rats , Rats, Sprague-Dawley , Soluble Guanylyl Cyclase/antagonists & inhibitors , Tetraethylammonium/pharmacology
13.
Sex Med ; 8(2): 132-155, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32201216

ABSTRACT

INTRODUCTION: Cardiometabolic syndrome (CMS), as a bunch of metabolic disorders mainly characterized by type 2 diabetes mellitus (T2DM), hypertension, atherosclerosis, central adiposity, and abdominal obesity triggering androgen deficiency, is one of the most critical threats to men. Although many significant preclinical and clinical findings explain CMS, new approaches toward common pathophysiological mechanisms and reasonable therapeutic targets are lacking. AIM: To gain a further understanding of the role of androgen levels in various facets of CMS such as the constellation of cardiometabolic risk factors including central adiposity, dyslipidemia, insulin resistance, diabetes, and arterial hypertension and to define future directions for development of effective therapeutic modalities. METHODS: Clinical and experimental data were searched through scientific literature databases (PubMed) from 2009 to October 2019. MAIN OUTCOME MEASURE: Evidence from basic and clinical research was gathered with regard to the causal impact and therapeutic roles of androgens on CMS. RESULTS: There are important mechanisms implicated in androgen levels and the risk of CMS. Low testosterone levels have many signs and symptoms on cardiometabolic and glycometabolic risks as well as abdominal obesity in men. CLINICAL IMPLICATIONS: The implications of the findings can shed light on future improvements in androgen levels and add potentially predictive risk for CMS, as well as T2DM, abdominal obesity to guide clinical management in the early stage. STRENGTHS & LIMITATIONS: This comprehensive review refers to the association between androgens and cardiovascular health. A limitation of this study is the lack of large, prospective population-based studies that analyze the effects of testosterone treatment on CMS or mortality. CONCLUSION: Low testosterone levels have several common features with metabolic syndrome. Thus, testosterone may have preventive role in the progress of metabolic syndrome and subsequent T2DM, abdominal obesity, and cardiovascular disease and likely affect aging men's health mainly through endocrine and vascular mechanisms. Further studies are necessary to evaluate the therapeutic interventions directed at preventing CMS in men. Kirlangic OF, Yilmaz-Oral D, Kaya-Sezginer E, et al. The Effects of Androgens on Cardiometabolic Syndrome: Current Therapeutic Concepts. Sex Med 2020;8:132-155.

14.
Neurourol Urodyn ; 39(4): 1087-1097, 2020 04.
Article in English | MEDLINE | ID: mdl-32150290

ABSTRACT

AIMS: To evaluate the impacts of hydrogen sulfide (H2 S) donor, sodium hydrogen sulfide (NaHS), and phosphodiesterase type-5 inhibitor (PDE5i), tadalafil per se and their combination treatment on partial bladder outlet obstruction (PBOO)-induced erectile dysfunction (ED). METHODS: Sprague-Dawley rats were equally divided into five groups: (a) sham-operated control; (b) PBOO; (c) PBOO-treated with NaHS (5.6 mg/kg/day, ip); (d) PBOO-treated with tadalafil (2 mg/kg/day, oral); and (e) PBOO-treated with combination of NaHS and tadalafil. The obstruction was created by urethral ligation for 6 weeks. In vivo erectile responses, in vitro relaxant and contractile responses in penile tissue as well as protein expression of nitric oxide synthases (NOS), H2 S synthesis enzymes, oxidative stress, hypoxia, fibrosis markers, and the smooth muscle/collagen ratio and apoptosis were analyzed. RESULTS: Combined treatment entirely returned increased bladder mass, reduced erectile responses, relaxation responses to acetylcholine, and electrical field stimulation in obstructed rats, while partial amelioration was observed after mono-treatment. Decreased neuronal NOS and 3-mercaptopiruvate transferase enzyme expressions in penile tissue from obstructed rats were also entirely restored by the combined treatment. Mono-treatment partially improved increased hypoxia, oxidative stress, fibrosis markers, decreased smooth muscle mass, and H2 S levels, while combined therapy completely recovered. CONCLUSIONS: The combination therapy with H2 S donor and PDE5i had positive effects on erectile responses through the improvement of ischemia-induced morphological and functional penile alterations in obstruction. H2 S and NO may likely play a synergistic role in the regulation of erectile function and have constructive effects on clinical outcomes in male patients with ED and benign prostatic hyperplasia/lower urinary tract symptoms.


Subject(s)
Erectile Dysfunction/drug therapy , Hydrogen Sulfide/therapeutic use , Penile Erection/drug effects , Phosphodiesterase 5 Inhibitors/therapeutic use , Tadalafil/therapeutic use , Urinary Bladder Neck Obstruction/complications , Animals , Disease Models, Animal , Erectile Dysfunction/etiology , Hydrogen/metabolism , Hydrogen/pharmacology , Hydrogen/therapeutic use , Hydrogen Sulfide/pharmacology , Male , Muscle, Smooth/drug effects , Phosphodiesterase 5 Inhibitors/pharmacology , Rats , Rats, Sprague-Dawley , Tadalafil/pharmacology , Treatment Outcome
15.
Aging Male ; 23(5): 1088-1097, 2020 Dec.
Article in English | MEDLINE | ID: mdl-31741421

ABSTRACT

OBJECTIVE: To evaluate the effect of the If channel inhibitor, ivabradine on human corpus cavernosum (HCC) smooth muscle tone. METHODS: HCC samples were obtained from erectile dysfunction(ED) patients (n = 12) undergoing penile prosthesis surgery. Concentration-response curves for ivabradine were exposed to various inhibitory and stimulatory agents. The relaxant and contractile responses to electrical field stimulation (EFS, 10 Hz and 80 Hz) were examined in the presence or absence of ivabradine (10 µM). HCN3 and HCN4 channel expression and localization were determined by Western blot and immunohistochemical analyses of HCC tissues. RESULTS: Increasing ivabradine concentrations dependently reduced the maximal contractile responses of isolated HCC strips induced by KCl (59.5 ± 2.5%) and phenylephrine (84.0 ± 9.8%), which was not affected by nitric oxide synthase and soluble guanylyl cyclase inhibitors after phenylephrine-induced contraction. Nifedipine and tetraethylammonium inhibited the maximum relaxation to ivabradine by 75% and 39.3%, respectively. Fasudil and sildenafil increased the relaxation response to ivabradine without altering the maximum response. Pre-incubation with ivabradine significantly increased relaxant responses to EFS (p < 0.01) and reduced the contractile tension evoked by EFS (72.3%) (p < 0.001). Ivabradine incubation did not affect the expression and localization of HCN3 and HCN4 channels in the HCC smooth muscle cells. CONCLUSIONS: Ivabradine exhibits a relaxant effect on HCC tissues, which is likely to be attributed to the blocking of L-type Ca2+ channels and the opening of K+ channels, independent of changes in the activation of the nitric oxide/cyclic guanosine monophosphate system. Inhibition of HCN channels localized in cavernosal smooth muscle cells may offer pharmacological benefits for patients with cardiovascular risk factors.


Subject(s)
Erectile Dysfunction , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels , Humans , Ivabradine/pharmacology , Male , Muscle Contraction , Nitric Oxide , Penile Erection , Penis
16.
Int. braz. j. urol ; 45(5): 1033-1042, Sept.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1040068

ABSTRACT

ABSTRACT Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.


Subject(s)
Humans , Animals , Male , Aged , Penis/drug effects , Acrolein/analogs & derivatives , Oils, Volatile/pharmacology , Cinnamomum zeylanicum/chemistry , Muscle Relaxation/drug effects , Penis/physiopathology , Phenylephrine/pharmacology , Vasoconstrictor Agents/pharmacology , Acrolein/pharmacology , Penile Erection/drug effects , Penile Erection/physiology , Reproducibility of Results , Analysis of Variance , Rats, Sprague-Dawley , Phosphodiesterase 5 Inhibitors/pharmacology , Sildenafil Citrate/pharmacology , Erectile Dysfunction/physiopathology , Erectile Dysfunction/drug therapy , Middle Aged , Muscle Relaxation/physiology
17.
Int Braz J Urol ; 45(5): 1033-1042, 2019.
Article in English | MEDLINE | ID: mdl-31408283

ABSTRACT

Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.


Subject(s)
Acrolein/analogs & derivatives , Cinnamomum zeylanicum/chemistry , Muscle Relaxation/drug effects , Oils, Volatile/pharmacology , Penis/drug effects , Acrolein/pharmacology , Aged , Analysis of Variance , Animals , Erectile Dysfunction/drug therapy , Erectile Dysfunction/physiopathology , Humans , Male , Middle Aged , Muscle Relaxation/physiology , Penile Erection/drug effects , Penile Erection/physiology , Penis/physiopathology , Phenylephrine/pharmacology , Phosphodiesterase 5 Inhibitors/pharmacology , Rats, Sprague-Dawley , Reproducibility of Results , Sildenafil Citrate/pharmacology , Vasoconstrictor Agents/pharmacology
18.
Low Urin Tract Symptoms ; 11(4): 232-240, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31207098

ABSTRACT

OBJECTIVE: This study evaluated the effect of human umbilical cord blood mononuclear cells (HUCB-MNCs) on bladder dysfunction in streptozotocin (STZ; 35 mg/kg, i.v.)-induced diabetic rats. METHODS: Adult male Sprague-Dawley rats (n = 30) were equally divided into three groups: control group, STZ-diabetic group, and HUCB-MNC-treated group (1 × 106 cells). HUCB-MNCs were isolated by density gradient centrifugation from eight healthy donors and injected into the corpus cavenosum in STZ-diabetic rats 4 weeks after the induction of diabetes. Studies were performed 4 weeks after HUCB-MNC or vehicle injection. In vitro organ bath studies were performed on bladder strips, whereas protein expression of hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and α-smooth muscle actin (SMA) in the bladder and the ratio of smooth muscle cells (SMCs) to collagen were determined using western blotting and Masson trichrome staining. RESULTS: Neurogenic contractions of detrusor smooth muscle strips were 55% smaller in the diabetic group than control group (P < 0.05); these contractions were normalized by HUCB-MNC treatment. In addition, HUCB-MNC treatment restored the impaired maximal carbachol-induced contractile response in detrusor strips in the diabetic group (29%; P < 0.05). HUCB-MNC treatment improved the KCl-induced contractile response in the diabetic bladder (68%; P < 0.05), but had no effect on ATP-induced contractile responses. Increased expression of HIF-1α and VEGF protein and decreased expression of α-SMA protein and the SMC/collagen ratio in diabetic rats were reversed by HUCB-MNC. CONCLUSION: Administration of HUCB-MNCs facilitates bladder function recovery, which is likely related to downregulation of HIF-1α expression and attenuation of fibrosis in STZ-diabetic rats.


Subject(s)
Diabetes Mellitus, Experimental/complications , Fetal Blood/cytology , Leukocytes, Mononuclear/physiology , Urinary Bladder Diseases/etiology , Actins/metabolism , Animals , Blotting, Western , Fetal Blood/physiology , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Male , Muscle Contraction/physiology , Muscle, Smooth/physiopathology , Rats , Rats, Sprague-Dawley , Urinary Bladder/metabolism , Urinary Bladder/physiopathology , Urinary Bladder Diseases/physiopathology , Urinary Bladder Diseases/therapy , Vascular Endothelial Growth Factor A/metabolism
19.
Nitric Oxide ; 85: 54-60, 2019 04 01.
Article in English | MEDLINE | ID: mdl-30768962

ABSTRACT

Rho-kinase activity is a key regulator in the maintenance of corporal vasoconstriction and penile detumescense. Also, importance of l-cysteine/H2S pathway in erectile tissue has been shown; however it is currently unknown the role RhoA/Rho-kinase pathway in H2S-induced inhibition in cavernosal tissue. We investigated the role of RhoA/Rho-kinase pathway in the inhibitory effect of l-cysteine and NaHS, as endogenous and exogenous H2S, respectively, on phenylephrine-induced contractions of mouse cavernosal strips. Phenylephrine, α1 receptor agonist, (10 nM-100 µM) induced a concentration-dependent contraction in CC. l-cysteine (endogenous H2S substrate; 10 mM) and exogenous H2S (NaHS; 1 mM) significantly inhibited the contractile response to phenylephrine (P < 0.05). Inhibition of CSE and CBS enzymes by PAG (10 mM) and AOAA (1 mM), respectively, significantly reversed the inhibitory effects of l-cysteine on phenylephrine-induced contraction (P < 0.05). Y-27632 (1 µM), a specific Rho-kinase inhibitor, significantly augmented the inhibitory effect of l-cysteine and NaHS on phenylephrine-induced contraction, and this inhibition was reversed by PAG and AOAA (P < 0.05). In addition, the formation of H2S was increased by approximately 1.8 fold over basal values after incubation of tissue homogenates with l-cysteine. Y-27632 significantly increased both basal and l-cysteine-induced H2S formation and this augmentation diminished by PAG and AOAA (P < 0.05). Furthermore, the pMYPT-1 expression was significantly decreased by l-cysteine, NaHS or Y-27632 alone. Also, pMYPT-1 expression was completely abolished by the l-cysteine/NaHS plus Y-27632 combination, and this inhibition was reversed by PAG and AOAA (P < 0.05). These results suggest that there is an interaction between Rho-kinase and H2S pathways. Rho-kinase may be, at least in part, inhibits CSE/CBS enzymes in mouse corpus cavernosal tissue; however, it is not excluded the other kinases such as PKC and Zip-kinase.


Subject(s)
Cysteine/pharmacology , Hydrogen Sulfide/pharmacology , Muscle Contraction/drug effects , Phenylephrine/antagonists & inhibitors , rho GTP-Binding Proteins/metabolism , rho-Associated Kinases/metabolism , Animals , Cysteine/metabolism , Hydrogen Sulfide/metabolism , Male , Mice , Phenylephrine/pharmacology , rhoA GTP-Binding Protein
20.
Andrologia ; 51(5): e13240, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30706510

ABSTRACT

Men with hypertension often develop erectile dysfunction (ED). The present study aimed to examine the effects of sodium hydrosulphide (NaHS), a hydrogen (H2 S) donor, treatment on ED in nitric oxide synthase (NOS) inhibitor (L-NAME)-induced hypertensive rats. Forty adult Sprague-Dawley rats were divided into four groups: control, NaHS (0.037 mg kg day-1 )-treated control, L-NAME-induced hypertension (40 mg kg day-1 ) and NaHS-treated L-NAME-induced hypertension. The ratio of intracavernosal pressure to mean arterial pressure and isometric tension of corpus cavernosum (CC) were measured. The penile expression of endothelial and neuronal NOS (eNOS and nNOS), inflammation markers [nuclear factor kappa B (NF-κB) and inhibitor kappa B alpha (IκBα)], H2 S-producing enzymes[cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE)], the smooth muscle/collagen ratio and H2 S concentrations were determined. The blood pressure was significantly increased in the hypertensive group, but not reversed by NaHS. The erectile response in hypertensive rats was partially prevented by NaHS. The relaxation response to electrical field stimulation was increased in CC from NaHS-treated hypertensive rats. NaHS treatment restored decreased protein expression of eNOS, nNOS and CSE as well as smooth muscle/collagen ratio and H2 S levels and increased NF-κB and IκBα protein expression in the penile tissue of hypertensive rats. NaHS promoted the recovery of erectile responses in hypertensive rats by improvement of neuronal function and downregulation of fibrosis and NF-κB signalling.


Subject(s)
Erectile Dysfunction/drug therapy , Hypertension/complications , Penile Erection/drug effects , Penis/drug effects , Sulfides/pharmacology , Animals , Cystathionine gamma-Lyase/metabolism , Disease Models, Animal , Erectile Dysfunction/etiology , Fibrosis/drug therapy , Fibrosis/pathology , Humans , Hydrogen Sulfide/pharmacology , Hypertension/chemically induced , Male , NG-Nitroarginine Methyl Ester/toxicity , Nitric Oxide Synthase Type I/metabolism , Nitric Oxide Synthase Type III/metabolism , Penis/metabolism , Penis/pathology , Rats , Rats, Sprague-Dawley , Sulfides/therapeutic use , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...