ArticleThe journal of sexual medicine2014
Sildenafil promotes eNOS activation and inhibits NADPH oxidase in the transgenic sickle cell mouse penis.
Article in The journal of sexual medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review by the EAU Sexual and Reproductive Health Guidelines Panel.International journal of impotence research · 2024Pooled it
- Randomized controlled trial of sildenafil for preventing recurrent ischemic priapism in sickle cell disease.The American journal of medicine · 2014Trial
- Successful Penile Replantation Following Amputation During Neonatal Circumcision: Case Report and Systematic Review.Plastic and reconstructive surgery. Global open · 2026Article
- Resveratrol and Its Nitric Oxide-Donor Hybrid as an Emerging Therapy for Oxidative-Stress-Driven Priapism in Sickle Cell Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Antioxidants: powering the fight against fetal hypoxia.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Investigation of PDE5 effect on NOS in nasal polyp pathophysiology.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Article
- Resveratrol attenuates the priapism phenotype in sickle cell mice by restoring NO-cGMP-PDE5 signaling and reducing NADPH oxidase 2 expression.Frontiers in pharmacology · 2025Article
- The endocannabinoid system's genetic polymorphisms in sickle cell anemia patients.Scientific reports · 2024Article
- Soluble guanylate cyclase stimulators and activators: new horizons in the treatment of priapism associated with sickle cell disease.Frontiers in pharmacology · 2024Review
- Tadalafil ameliorates bladder overactivity by restoring insulin-activated detrusor relaxation via the bladder mucosal IRS/PI3K/AKT/eNOS pathway in fructose-fed rats.Scientific reports · 2021Article
- TSPO ligand FGIN-1-27 controls priapism in sickle cell mice via endogenous testosterone production.Journal of cellular physiology · 2021Article
- Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress.The journal of sexual medicine · 2019Article
- Biphasic Effect of Sildenafil on Energy Sensing is Mediated by Phosphodiesterases 2 and 3 in Adipocytes and Hepatocytes.International journal of molecular sciences · 2019Article
- Molecular Profile of Priapism Associated with Low Nitric Oxide Bioavailability.Journal of proteome research · 2018Article
- Evolving treatment paradigms in sickle cell disease.Hematology. American Society of Hematology. Education Program · 2017Review
- The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Advances in the understanding of priapism.Translational andrology and urology · 2017Review
- Constitutive NOS uncoupling and NADPH oxidase upregulation in the penis of type 2 diabetic men with erectile dysfunction.Andrology · 2017Article
- A microdialysis method to measure in vivo hydrogen peroxide and superoxide in various rodent tissues.Methods (San Diego, Calif.) · 2016Article
- Transnitrosylation: A Factor in Nitric Oxide-Mediated Penile Erection.The journal of sexual medicine · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
introductionSickle cell disease (SCD)-associated vasculopathy in the penis is characterized by aberrant nitric oxide and phosphodiesterase (PDE) 5 signaling, and by increased oxidative stress. Preliminary clinical trials show that continuous treatment with PDE5 inhibitor sildenafil unassociated with sexual activity decreases priapic activity in patients with SCD. However, the mechanism of its vasculoprotective effect in the penis remains unclear.
aimsWe evaluated whether continuous administration of PDE5 inhibitor sildenafil promotes eNOS function at posttranslational levels and decreases superoxide-producing enzyme NADPH oxidase activity in the sickle cell mouse penis.
methodsSCD transgenic mice were used as an animal model of SCD. WT mice served as controls. Mice received treatment with the PDE5 inhibitor sildenafil (100 mg/kg/day) or vehicle for 3 weeks. eNOS phosphorylation on Ser-1177 (positive regulatory site), eNOS interactions with heat-shock protein 90 (HSP90) (positive regulator), phosphorylated AKT (upstream mediator of eNOS phosphorylation on Ser-1177), an NADPH oxidase catalytic subunit gp91(phox), and a marker of oxidative stress (4-hydroxy-2-nonenal [HNE]) were measured by Western blot.
main outcome measuresEffect of continuous sildenafil treatment on eNOS posttranslational activation, NADPH oxidase catalytic subunit, and oxidative stress in the penis of the sickle cell mouse.
resultsContinuous treatment with sildenafil reversed (P < 0.05) the abnormalities in protein expressions of P-eNOS (Ser-1177), eNOS/HSP90 interaction, P-AKT, protein expression of gp91(phox), and 4-HNE, in the sickle cell mouse penis. Sildenafil treatment of WT mice did not affect any of these parameters.
conclusionOur findings that sildenafil enhances eNOS activation and inhibits NADPH oxidase function in the sickle cell mouse penis offers a vasculoprotective molecular basis for the therapeutic effect of sildenafil in the penis in association with SCD.
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Registered trials
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