ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Bimodal effect of oxidative stress in internal anal sphincter smooth muscle.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Dual ROS modulation by MnOTheranostics · 2026Article
- Obesity Is Independently Associated With Increased Risk of Fecal Incontinence and Altered Rectal Sensitivity.The American journal of gastroenterology · 2025Article
- Weight-adjusted-waist index is positively associated with fecal incontinence: a cross-sectional study.Journal of health, population, and nutrition · 2025Article
- 3D spheroids versus 2D-cultured human adipose stem cells to generate smooth muscle cells in an internal anal sphincter-targeting cryoinjured mouse model.Stem cell research & therapy · 2024Article
- Centrally Distributed Adiposity as a Modifiable Risk Factor for Fecal Incontinence: United States Population-based Analysis.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2024Article
- The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders.Antioxidants (Basel, Switzerland) · 2021Review
- Contractile function of the cervix plays a role in normal and pathological pregnancy and parturition.Medical hypotheses · 2020Article
- Changes in murine anorectum signaling across the life course.Neurogastroenterology and motility · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Changes in oxidative stress may affect basal tone and relaxation of the internal anal sphincter (IAS) smooth muscle in aging. We examined this issue by investigating the effects of the oxidative stress inducer 6-anilino-5,8-quinolinedione (LY-83583) in basal as well as U-46619-stimulated tone, and nonadrenergic, noncholinergic (NANC) relaxation in rat IAS. LY-83583, which works via generation of reactive oxygen species in living cells, produced a bimodal effect in IAS tone: lower concentrations (0.1 nM to 10 μM) produced a concentration-dependent increase, while higher concentrations (50-100 μM) produced a decrease in IAS tone. An increase in IAS tone by lower concentrations was associated with an increase in RhoA/Rho kinase (ROCK) activity. This was evident by the increase in RhoA/ROCK in the particulate fractions, in ROCK activity, and in the levels of phosphorylated (p) (Thr696)-myosin phosphatase target subunit 1 and p(Thr18/Ser19)-20-kDa myosin light chain. Conversely, higher concentrations of LY-83583 produced inhibitory effects on RhoA/ROCK. Interestingly, both the excitatory and inhibitory effects of LY-83583 in the IAS were reversed by superoxide dismutase. The excitatory effects of LY-83583 were found to resemble those with neuronal nitric oxide synthase (nNOS) inhibition by l-NNA, since it produced a significant increase in the IAS tone and attenuated NANC relaxation. These effects of LY-83583 and l-NNA were reversible by l-arginine. This suggests the role of nNOS inhibition and RhoA/ROCK activation in the increase in IAS tone by LY-83583. These data have important implications in the pathophysiology and therapeutic targeting of rectoanal disorders, especially associated with IAS dysfunction.
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