Related Experiment Video
Updated: Jul 3, 2026
En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
Published on: February 25, 2016
Blockade of endogenous proinflammatory cytokines ameliorates endothelial dysfunction in obese Zucker rats
Hiroaki Nishimatsu1, Etsu Suzuki, Ryo Takeda
1Department of Urology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Abstract:
To study the role of endogenous proinflammatory cytokines in endothelial dysfunction in diabetes, we administered semapimod, an inhibitor of proinflammatory cytokine production, to obese Zucker (OZ) rats, and examined its effect on endothelium-dependent vasorelaxation. Endothelium-dependent vasorelaxation induced by acetylcholine and adrenomedullin (AM) was significantly reduced in OZ rats compared to a control group of lean Zucker rats. Semapimod significantly restored endothelium-dependent vasorelaxation in OZ rats. This effect of semapimod was well correlated with the reduction in the serum concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and C-reactive protein, as well as with the recovery of AM-induced Akt phosphorylation and cGMP production. Furthermore, acute administration of TNF-alpha significantly suppressed endothelium-dependent vasorelaxation and AM-induced cGMP production. These results implicate endogenous proinflammatory cytokines, especially TNF-alpha, in endothelial dysfunction in diabetes, and indicate that blockade of these cytokines will be a promising strategy for inhibiting the progression of vascular inflammation.
Insights
Inhibiting proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), improved endothelial dysfunction in diabetic rats. Blocking these cytokines offers a promising strategy against vascular inflammation.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Immunology
Background:
- Endothelial dysfunction is a key complication in diabetes.
- Proinflammatory cytokines are implicated in diabetes-related vascular damage.
Purpose of the Study:
- To investigate the role of endogenous proinflammatory cytokines in diabetes-induced endothelial dysfunction.
- To evaluate the therapeutic potential of semapimod, a cytokine inhibitor, in restoring vascular function.
Main Methods:
- Obese Zucker rats (diabetic model) and lean Zucker rats (control) were used.
- Semapimod was administered to obese rats to inhibit cytokine production.
- Endothelium-dependent vasorelaxation, cytokine levels, Akt phosphorylation, and cGMP production were assessed.
Main Results:
- Obese rats exhibited significantly reduced vasorelaxation compared to lean rats.
- Semapimod treatment restored vasorelaxation in obese rats.
- This improvement correlated with reduced serum proinflammatory cytokines (TNF-alpha, IL-6, CRP) and restored AM-induced Akt phosphorylation and cGMP production.
- Exogenous TNF-alpha administration impaired vasorelaxation and cGMP production.
Conclusions:
- Endogenous proinflammatory cytokines, particularly TNF-alpha, contribute significantly to endothelial dysfunction in diabetes.
- Blocking these cytokines represents a promising therapeutic strategy for mitigating vascular inflammation and its complications in diabetes.
