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Peer-reviewedCC BY 4.0PLOS One

Endothelial-related gene expression profile of muscle adaptation to high-intensity interval training in arterial hypertension

1 more authors
7 affiliations
  1. 1Department of Medicine, University of Western São Paulo, UNOESTE, Presidente Prudente, São Paulo, Brazil
  2. 2Health Science Program, University of Western São Paulo, UNOESTE, Presidente Prudente, São Paulo, Brazil
  3. 3Animal Science Program, University of Western São Paulo, UNOESTE, Presidente Prudente, São Paulo, Brazil
  4. 4Faculties of Dracena, UNIFADRA, Dracena, São Paulo, Brazil
  5. 5Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, USP, São Paulo, Brazil
  6. 6Experimental Research Unity, Faculty of Medicine, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil
  7. 7Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America

Abstract

Hypertension and aging are associated with endothelial dysfunction in skeletal muscle, potentially compromising exercise capacity. Although high-intensity interval training (HIIT) has been proposed as an effective non-pharmacological strategy for individuals with hypertension, its effects on endothelial-related markers in aging skeletal muscle remain unclear This study investigated the impact of HIIT on endothelial-related gene expression in hypertensive aging rats. Twenty male 12-month-old spontaneously hypertensive rats were assigned to sedentary (n = 10) or trained (n = 10) groups. The training protocol (50 min/day, 5 times/week) was performed for 8 weeks, on a treadmill adapted for rodents. Gene expression of nitric oxide synthase 3 (NOS3), vascular endothelial growth factor (VEGF), endothelin-1 (EDN1), and phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) was assessed by reverse transcription quantitative polymerase chain reaction and by reanalysis of transcriptomic datasets available in the Gene Expression Omnibus (GSE109657 and GSE163356). Eight weeks of HIIT reduced blood pressure and improved physical performance, without altering the expression of NOS3, VEGF, EDN1, and PIK3R2 in the soleus and diaphragm muscles. These findings are consistent with an independent transcriptomic dataset from vastus lateralis biopsies of healthy subjects performing HIIT protocols (4 times/week for 6 weeks); however, changes were identified in NOS3, VEGF, and PIK3R2 genes in the vastus lateralis muscle after an HIIT protocol performed 3 times/week for 3 weeks. Collectively, the results indicate that HIIT improves functional capacity and blood pressure regulation in hypertensive aging rats, without concomitant changes in endothelial-related gene expression. These results are comparable with those found in healthy individuals undergoing a similar period of HIIT.

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BibTeX
@article{camilo2026endothelialrelated,
  title = {{Endothelial-related gene expression profile of muscle adaptation to high-intensity interval training in arterial hypertension}},
  author = {Helen Louisi Camilo and Natália Zamberlan Ferreira and Luciana Sanae Ota and Antônio Cláudio Bongiovani and Ines Cristina Giometti and Aline de Oliveira Santos and Paula Paccielli Freire and Katashi Okoshi and Rafael S. Floriano and Ivan J. Vechetti and Dijon Henrique Salomé de Campos and Marina Politi Okoshi and Francis Lopes Pacagnelli},
  journal = {PLOS One},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0358696},
  url = {https://doi.org/10.1371/journal.pone.0358696},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Endothelial-related gene expression profile of muscle adaptation to high-intensity interval training in arterial hypertension
AU  - Helen Louisi Camilo
AU  - Natália Zamberlan Ferreira
AU  - Luciana Sanae Ota
AU  - Antônio Cláudio Bongiovani
AU  - Ines Cristina Giometti
AU  - Aline de Oliveira Santos
AU  - Paula Paccielli Freire
AU  - Katashi Okoshi
AU  - Rafael S. Floriano
AU  - Ivan J. Vechetti
AU  - Dijon Henrique Salomé de Campos
AU  - Marina Politi Okoshi
AU  - Francis Lopes Pacagnelli
PY  - 2026
DA  - 2026/10/14
JO  - PLOS One
DO  - 10.1371/journal.pone.0358696
UR  - https://doi.org/10.1371/journal.pone.0358696
AB  - Hypertension and aging are associated with endothelial dysfunction in skeletal muscle, potentially compromising exercise capacity. Although high-intensity interval training (HIIT) has been proposed as an effective non-pharmacological strategy for individuals with hypertension, its effects on endothelial-related markers in aging skeletal muscle remain unclear This study investigated the impact of HIIT on endothelial-related gene expression in hypertensive aging rats. Twenty male 12-month-old spontaneously hypertensive rats were assigned to sedentary (n = 10) or trained (n = 10) groups. The training protocol (50 min/day, 5 times/week) was performed for 8 weeks, on a treadmill adapted for rodents. Gene expression of nitric oxide synthase 3 (NOS3), vascular endothelial growth factor (VEGF), endothelin-1 (EDN1), and phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) was assessed by reverse transcription quantitative polymerase chain reaction and by reanalysis of transcriptomic datasets available in the Gene Expression Omnibus (GSE109657 and GSE163356). Eight weeks of HIIT reduced blood pressure and improved physical performance, without altering the expression of NOS3, VEGF, EDN1, and PIK3R2 in the soleus and diaphragm muscles. These findings are consistent with an independent transcriptomic dataset from vastus lateralis biopsies of healthy subjects performing HIIT protocols (4 times/week for 6 weeks); however, changes were identified in NOS3, VEGF, and PIK3R2 genes in the vastus lateralis muscle after an HIIT protocol performed 3 times/week for 3 weeks. Collectively, the results indicate that HIIT improves functional capacity and blood pressure regulation in hypertensive aging rats, without concomitant changes in endothelial-related gene expression. These results are comparable with those found in healthy individuals undergoing a similar period of HIIT.
SN  - 1932-6203
ER  -