ArticleProceedings of the National Academy of Sciences of the United States of America2002
Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 1 of them a synthesis that pooled it.
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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
143 citing papers in PubMed, 1 synthesis or guideline pooled it, 377 citations in OpenAlex.
- Electrical stimulation for erectile dysfunction: a systematic review and meta-analysis of RCTs.International journal of impotence research · 2026Pooled it
- Comparative Effectiveness of Electrical Stimulation and Aerobic Exercise in the Management of Erectile Dysfunction: A Randomized Clinical Trial.Ethiopian journal of health sciences · 2020Trial
- An initial study on the effect of functional electrical stimulation in erectile dysfunction: a randomized controlled trial.International journal of impotence research · 2018Trial
- Low dose daily versus on-demand high dose tadalafil in diabetic patients with erectile and ejaculatory dysfunction.International journal of impotence research · 2018Trial
- Impairment of shear-stress-mediated vasodilation of cavernous arteries in erectile dysfunction.International journal of impotence research · 2004Trial
- Occupational cadmium exposure and endocrine biomarker alterations in male workers: a cross-sectional study.BMC endocrine disorders · 2026Article
- Update on the prevalence and pathophysiology of sickle cell priapism: a narrative review.International journal of impotence research · 2026Review
- Astaxanthin mitigates radiation-induced erectile dysfunction: protective effects on corpus cavernosum in a rat model.International journal of impotence research · 2026Article
- FN1-associated cavernous endothelial remodeling induced by bisphenol A: relevance to erectile dysfunction and attenuation by baicalin.Frontiers in nutrition · 2026Article
- Advances in immune-inflammatory interactions within the testicular-penile microenvironment of varicocele patients: molecular mechanisms underlying erectile dysfunction and spermatogenic impairment.Frontiers in endocrinology · 2026Review
- Erectile dysfunction, type 2 diabetes, and cardiovascular disease: a narrative review and insights from a global real-world cohort analysis.Frontiers in clinical diabetes and healthcare · 2026Review
- Immune-mediated skin diseases and erectile dysfunction: mechanisms and multidisciplinary management.Frontiers in immunology · 2026Review
- The Impact of Glucagon-like Peptide-1 Receptor Agonists on Erectile Function: Friend or Foe?Biomolecules · 2025Review
- Dimethyl Fumarate Improves Diabetic Erectile Dysfunction in Rats via Nrf2-Mediated Suppression of Penile Endothelial Oxidative Stress.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- N-Homocysteinylation of HMGB1/2 Promotes Corpus Cavernosum Endothelial Senescence in Erectile Dysfunction.International journal of biological sciences · 2025Article
- The endocannabinoid system's genetic polymorphisms in sickle cell anemia patients.Scientific reports · 2024Article
- In vitro effect of relaxin in the rat corpus cavernosum under hyperglycemic and normoglycemic conditions.International journal of impotence research · 2024Article
- Poweromin X Ten, a polyherbal formulation improves male sexual function:F1000Research · 2024Article
- Angiogenic potential of skeletal muscle derived extracellular vesicles differs between oxidative and glycolytic muscle tissue in mice.Scientific reports · 2023Article
- Ultrasound-targeted microbubble destruction mediates PDE5i/NO integration for cavernosum remodeling and penile rehabilitation.Bioengineering & translational medicine · 2023Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
In the penis, nitric oxide (NO) can be formed by both neuronal NO synthase and endothelial NOS (eNOS). eNOS is activated by viscous drag/shear stress in blood vessels to produce NO continuously, a process mediated by the phosphatidylinositol 3-kinase (PI3kinase)/Akt pathway. Here we show that PI3-kinase/Akt physiologically mediates erection. Both electrical stimulation of the cavernous nerve and direct intracavernosal injection of the vasorelaxant drug papaverine cause rapid increases in phosphorylated (activated) Akt and eNOS. Phosphorylation is diminished by wortmannin and LY294002, inhibitors of PI3-kinase, the upstream activator of Akt. The two drugs also reduce erection. Penile erection elicited by papaverine is reduced profoundly in mice with targeted deletion of eNOS. Our findings support a model in which rapid, brief activation of neuronal NOS initiates the erectile process, whereas PI3-kinase/Akt-dependent phosphorylation and activation of eNOS leads to sustained NO production and maximal erection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.