Exercise training‐induced adaptations of vascular smooth muscle vasodilatory function are absent in muscle arterioles from rats lacking the nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) gene
Authors: Wahl Jake Anthony , Park Hyerim , Restrepo Alexis , Dewell Isabella , Wahl John , Maraj Joshua , Peterson William , Reid‐Foley Emily , Ballehr Kelsey , VanFleet Alexander , Bedwell Kristen , Medarev Steven , Schartz Kaley , Sadowsky Dylan , Delp Michael , Geurts Aron , Muller‐Delp Judy 
Published: June 2021

Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is a transcription factor that is crucial in maintaining cellular redox homeostasis. Nrf2 protein increases with exercise training in skeletal muscle. Adaptations of the vasculature are often linked to changes in the metabolic profile of skeletal muscle. We hypothesized that deletion of Nrf2 would negate or reduce exercise training‐induced adaptations of arterioles from the soleus muscle. To test this hypothesis, we exercise trained wild type Sprague‐Dawley (WT) rats, and their littermates that were lacking the Nrf2 gene (Nrf2KO). Rats were either exercise trained (EX) on a motor‐driven treadmill 5 days/wk or remained sedentary (SED) in their cages for 10–12 weeks. A mixed moderate aerobic and high‐intensity interval training protocol was utilized. At the end of the training period, soleus muscle arterioles were isolated for assessment of vascular reactivity. Responsiveness to potassium chloride (KCl), phenylephrine, and the NO donor, Diethylamine‐NONO‐ate were evaluated. In resistance soleus muscle arterioles from WT rats, constriction to high concentrations of KCl (80–100 mM) was reduced (WT EX vs WT SED; P<0.05) by exercise training. In contrast, vasodilatory responsiveness to low concentrations of KCl (10–20 mM) was increased (WT EX vs WT SED; P<0.05) by exercise training in resistance arterioles from the soleus muscle of WT rats. Exercise training also increased vasodilatory responsiveness (WT EX vs WT SED; P=0.02) to DEA‐NONO‐ate in soleus muscle arterioles from WT rats. These exercise training‐induced adaptations were absent in soleus muscle arterioles from Nrf2KO rats. Vasoconstrictor responses to phenylephrine were not changed by exercise training in soleus muscle arterioles from WT rats, but tended to increase with exercise training in arterioles from Nrf2KO rats. These data suggest that exercise training enhances vasodilatory responsiveness of the vascular smooth muscle in soleus muscle arterioles from WT rats; however, exercise training‐induced enhancement of vasodilation in smooth muscle is absent in soleus muscle arterioles from Nrf2KO rats. This lack of vasodilatory adaptation may contribute to greater vasoconstrictor responses in arterioles from exercise‐trained Nrf2KO rats. Further experiments in denuded arterioles are needed to definitively determine whether these exercise training‐induced adaptations occur in the vascular smooth muscle or in the endothelium of soleus muscle arterioles from WT and Nrf2KO rats.

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NIH Grant Number R15AG055029

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.