Molecular Pathways Involved in Aerobic Exercise Training Enhance Vascular Relaxation

Author(s)

Paula, Suliana M. ; Fernandes, Tiago ; Couto, Gisele K. ; Jordao, Maria T. ; Oliveira, Edilamar M. ; Michelini, Lisete C. ; Rossoni, Luciana Venturini

• Document type: Journal article
• Source: MEDICINE AND SCIENCE IN SPORTS AND EXERCISE; v. 52, n. 10, p. 10-pg., 2020-10-01.

Abstract

Purpose The beneficial effects of exercise training on the cardiovascular system are well known. Because our knowledge of exercise-induced vascular function is still limited, we aimed to uncover the molecular mechanisms conditioning the improved vascular relaxation in muscular arteries. Methods Male Wistar-Kyoto rats with the same ability to run on a treadmill after maximal exercise tests were allocated to the following two groups: trained (Tr) (treadmill, 50%-60% of maximal capacity, 5 d center dot wk(-1)) and untrained (UnTr). After 13 wk, the femoral arteries were harvested and used for functional, structural, and molecular analyses. Results Acetylcholine (ACh)-induced relaxation and nitric oxide (NO) production were enhanced in arteries from Tr rats compared with UnTr rats. Tr arteries exhibited reduced microRNA (miRNA)-124a expression (whose target is caveolin-1), increased the density of caveolae aligned along the sarcolemma and reduced ACh-induced relaxation in the presence of methyl-beta-cyclodextrin, which disrupts caveolae. Higher endothelial NO synthase (eNOS) expression with lower miRNA-155 expression and the posttranslational modification of eNOS (phosphorylation of stimulatory Ser1177 and dephosphorylation of inhibitory Thr495) by the PI3-kinase/Akt1/2/3 pathway also contributed to the higher NO production induced by exercise training. Furthermore, increased Cu/Zn- and extracellular-superoxide dismutase expression and enhanced effects of their pharmacological scavenger activity on the ACh-induced response were observed in Tr arteries. Conclusions The results of the present study provide a molecular basis for exercise-induced NO bioavailability in healthy femoral arteries. Increased caveolae domain and eNOS expression/activity in Tr arteries are associated with downregulation of miRNA-124a and -155, as well as are involved with higher antioxidant defense, subsequently inducing a favorable endothelium-dependent milieu in Tr arteries. (AU)

• FAPESP's process: 10/50048-1 - Cellular and functional bases of exercise in cardiovascular diseases
• Grantee: Carlos Eduardo Negrão
• Support Opportunities: Research Projects - Thematic Grants