New Approaches in Exercise Physiology

Effects of Exercise on the Microvascular Response, Endothelial Health, and NO Bioavailability: A Systematic Review and Meta-Analysis of Preclinical Evidence

Document Type : Review Article

Authors

Ameer F ahem Hassan Al-Shaeef 1
Reza Farzizadeh 2
Farnaz Seifi-askishahr 1

1 Department of Physical Education and Sport Sciences, Faculty of Education Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran.

2 Department of Sport Physiology, Faculty of Educational Science and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran.

https://doi.org/10.22054/nass.2026.93581.1241
Abstract
Purpose: Mechanistic evidence from animal models is essential for understanding exercise-induced vascular adaptations, yet the translatability of these findings to clinical settings remains uncertain. This systematic review and meta-analysis quantified the effects of exercise training on endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) levels in animal models. Method: A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library (January 2000–September 2025) was done. The review protocol was registered with PROSPERO (CRD420251144669). A random-effects model (REML) was used for meta-analysis, and SYRCLE's Risk of Bias tool assessed study quality.
Results: Exercise training significantly increased eNOS levels (SMD = 0.99, 95% CI: 0.55–1.44, p < 0.001). In contrast, no significant effects were observed for NO (SMD = −1.26, 95% CI: −2.89–0.37, p = 0.13). Subgroup analyses showed that longer exercise duration (≥5 weeks; SMD = 2.25, p < 0.001) and specific modalities such as treadmill running (SMD = 1.92) and swimming (SMD = 4.59) were associated with substantially greater eNOS upregulation. Considerable heterogeneity was observed across most outcomes (I² > 85%). Conclusion: Exercise training effectively upregulates eNOS expression in animal models, particularly with interventions lasting five weeks or longer and with structured modalities like treadmill and swimming. However, the absence of significant effects on NO level, despite increased eNOS, reveals a translational gap that warrants further mechanistic investigation.

Keywords

Exercise training
Endothelial nitric oxide synthase
Nitric oxide bioavailability
Systematic review
Animal models
Subjects
New Approaches in Exercise Physiology
Volume 9, Issue 17
June 2027
Pages 5-58

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