Association of nNOS and Rho-kinase with age-associated erectile dysfunction in Sprague-Dawley rats

Ding, Zhibo; Shen, Xue; Li, Yunfei

doi:10.3892/etm.2017.4064

Cited by 8 publications

(11 citation statements)

References 25 publications

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“…Erectile dysfunction (ED) is a prevailing health problem that compromises the quality of life of men and their partners (Shamloul & Ghanem, ). It was reported that aging is an independent predictor of ED, irrespective of comorbid diseases (Ding et al ., ). The Massachusetts Male Aging Study demonstrated that the annual incidence rate of ED was 1.2% in men aged between 40 and 49 years and the rate increased to 4.6% in men aged between 60 and 69 years (Johannes et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Adipose‐derived stem cells improve erectile function partially through the secretion of IGF‐1, bFGF, and VEGF in aged rats

Yang

Zhang

Zang³

et al. 2018

Andrology

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Adipose-derived stem cells (ADSCs) have recently been considered as a promising therapy for erectile dysfunction (ED). However, the mechanism of ADSC-based therapy is unclear. Insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) secreted by ADSCs were assessed in vitro. Sixteen 24-month-old male Sprague-Dawley rats were used for comparative analysis of 2-week treatment with labeled ADSCs or PBS. Eight additional 5-month-old rats were used as a young rat group. At 2 weeks post-transplantation, all rats were analyzed for erectile function, cavernous IGF-1, bFGF and VEGF levels, and penile histology. Conditioned medium and co-culture systems were used in cell experiments to detect how growth factors act on corpus cavernosum smooth muscle cells (CCSMCs) under oxidative stress conditions via crystal violet staining and immunofluorescence staining. We found that ADSCs secreted significantly higher IGF-1, bFGF, and VEGF levels in culture medium compared with basal medium. Compared with young rats, untreated aged rats had significantly lower Max ICP/MAP and ADSC treatment significantly increased the ratio. Immunofluorescence staining demonstrated a small number of labeled ADSCs in the corpus cavernosum. The untreated aged rats showed significantly decreased cavernous IGF-1, bFGF, and VEGF levels and significantly decreased contents of cavernous smooth muscle and endothelium compared with young rats. ADSC treatment partially normalized these alterations. In cell experiments, the groups receiving growth factor neutralizing antibody separately or combined had significantly decreased numbers of CCSMCs compared with control groups. These results indicated that ADSC treatment may improve aging-related ED partially through the secretion of IGF-1, bFGF, and VEGF.

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Section: Introductionmentioning

confidence: 97%

Adipose‐derived stem cells improve erectile function partially through the secretion of IGF‐1, bFGF, and VEGF in aged rats

Yang

Zhang

Zang³

et al. 2018

Andrology

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“…A related study showed a marked decline in eNOS protein expression with age, while the Rho-kinase protein level was increased and, in particular, the eNOS/Rho-kinase ratio decreased with age. 35 Involvement of Rho-kinase in ED pathogenesis was also evaluated by animal model with HF. 17 The results showed that the rats developed ED after ligation of the left anterior descending coronary artery, as demonstrated by decreased ICP/MAP responses.…”

Section: Resultsmentioning

confidence: 99%

“… Conclusion: Age-associated ED was therefore correlated with decreased eNOS and increased Rho-kinase. 35 Vasculogenic and post-radical prostatectomy induced ED in human subjects Samples were collected from individuals who undergo penile surgery for Peyronie’s disease and from men with ED who underwent penile prosthesis implantation. ED was categorized into vasculogenic and post-RP subtypes.…”

Section: Resultsmentioning

confidence: 99%

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<p>A Systematic Review on Rho-Kinase as a Potential Therapeutic Target for the Treatment of Erectile Dysfunction</p>

Zewdie

Ayza

Tesfaye

et al. 2020

RRU

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Background: Erectile dysfunction (ED) is a common clinical condition with limited treatment options. The main aim of the present systematic review was to synthesize information on Rho-kinase as a novel therapeutic approach for the treatment of ED. Methods: We performed a systematic literature study in PubMed, Google Scholar and Scopus. Included studies were original articles studied the role of Rho-kinase in the pathogenesis and/or new treatment approach for ED in animal models and clinical studies, published between 2014 and 2019. Data derived from each study were study design used, interventions applied and main treatment outcomes. The quality of the selected articles was assessed by CAMARADES criteria and data were analyzed using descriptive statistics. Results: A total of 1067 original articles were retrieved in the given period and eighteen papers met our inclusion criteria. Five articles explain the role of Rho-kinase in ED pathogenesis using different models such as cavernous nerve crush injury, heart failureinduced ED, vasculogenic and post-radical prostatectomy ED, diabetes-induced ED and agerelated ED. Other ten papers explain the role of novel drugs evaluated for ED treatment by targeting Rho-kinase as a new approach for ED therapy. The rest three papers discuss the role of plant extracts used by traditional society for the treatment of ED and assess their potential function in targeting Rho-kinase in animal models. The penile erectile functional index has shown that the ratio of intracavernosal pressure to mean arterial pressure (ICP/MAP) was decreased due to age and various chronic diseases. Whilst, ROCK I and ROCK II expression were increased. Western blot findings have also shown that ROCK II and MYPT-1 phosphorylation rates increased in cavernous tissue after ED induction. Besides, compounds which can inhibit the action of Rho-kinase activity showed relaxation of the corpus cavernosum, decrease in corporal fibrosis, and alleviate increased apoptosis and caspase-3 activity in an NO-independent manner. Moreover, histological and molecular dysregulation have been improved by inhibition of Rho-kinase. Conclusion: Targeting Rho-kinase may be a possible target for the treatment of ED secondary to specific causes, and Rho-kinase inhibitors may be a new drug family for the treatment of ED. However, this requires further studies for in-depth understanding.

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“…Each nerve was stimulated for 60 seconds, and the maximal ICP generated with the corresponding MAP (the ICP/MAP ratio) was recorded for each side. 22…”

Section: Measurement Of Intracavernosal Pressure (Icp) and Mean Artmentioning

confidence: 99%

MyD88 overexpression deteriorates Ang‐II‐induced ED via upregulating MPO and COX2 and downregulating eNOS in the corpus cavernosum of rats

Zhang

Jia

et al. 2018

J of Cellular Biochemistry

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Introduction Erectile dysfunction (ED) is a common sexual problem for men and the exploration of its treatment is still in mire demand. We aim to investigate the role of the Toll‐like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88) signaling pathway in the pathogenesis of angiotensin II (Ang‐II) induced ED. Methods Male Sprague‐Dawlay rats were treated with Ang‐II and intracavernous pressure (ICP) was measured to confirm the occurrence of ED. The corpus cavernosum penises of rats were transfected with plasmids to overexpressed MyD88. Inflammatory and vascular parameters including myeloperoxidase (MPO), cyclooxygenase2 (COX2), endothelial nitric oxide synthase (eNOS), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), and cytokines in treated and untreated ED rats were measured. Flow cytometry was used to determine the apoptosis of endothelial cells of corpus cavernosum penises of rats. Results Ang‐II‐induced ED rats were found to contain upregulated TLR4, MyD88, MPO, and COX2, and downregulated eNOS. MyD88 overexpression deteriorates cavernous structural damage, reduces ICP and ICP/MAP values and reverses the therapeutic effect of anti‐TLR4 antibodies in rats with Ang‐II‐induced ED. Moreover, overexpression of MyD88 further upregulated MPO and COX2, downregulated eNOS, promoted oxidative stress, inflammation, and cell apoptosis rate via positively regulating the TLR4/MyD88 signaling pathway, while anti‐TLR4 antibodies downregulated MPO and COX2, upregulated eNOS, suppressed oxidative stress, inflammation, and cell apoptosis rate via inactivating the TLR4/MyD88 signaling pathway in the rat corpus cavernosum penises. Furthermore, MyD88 overexpression promotes oxidative stress and inflammation and reverses the effect of anti‐TLR4 antibodies in the penis of ED rats. Conclusion MyD88 overexpression deteriorates Ang‐II‐induced ED via upregulating MPO and COX2 and downregulating eNOS in the corpus cavernosum rats.

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Association of nNOS and Rho-kinase with age-associated erectile dysfunction in Sprague-Dawley rats

Cited by 8 publications

References 25 publications

Adipose‐derived stem cells improve erectile function partially through the secretion of IGF‐1, bFGF, and VEGF in aged rats

Adipose‐derived stem cells improve erectile function partially through the secretion of IGF‐1, bFGF, and VEGF in aged rats

<p>A Systematic Review on Rho-Kinase as a Potential Therapeutic Target for the Treatment of Erectile Dysfunction</p>

MyD88 overexpression deteriorates Ang‐II‐induced ED via upregulating MPO and COX2 and downregulating eNOS in the corpus cavernosum of rats

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