Exercise training‐induced enhancement of coronary vasodilatory function is absent in rats lacking the transcription factor, Nrf2

Abstract

Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is a transcription factor that is crucial in maintaining cellular redox homeostasis. Aerobic exercise training has been reported to enhance vasodilatory responses of coronary arterioles through signaling that involves reactive oxygen species. We hypothesized that deletion of Nrf2 would alter vasodilatory responses of coronary arterioles and limit exercise training‐induced adaptations of coronary vasodilatory function. We exercise trained wild type (WT) Sprague‐Dawley 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, coronary arterioles were isolated and vasodilatory responses to intraluminal flow (pressure differences from 2–60 cm H2O) and the exogenous nitric oxide donor, Dea‐NONO‐ate (1×10−9–1×10−4M), were evaluated. Endothelium‐dependent vasodilation to intraluminal flow was not altered by either deletion of Nrf2 or by exercise training. In contrast, endotheliumin‐dependent vasodilation to Dea‐NONO‐ate, was reduced in coronary arterioles from Nrf2 rats as compared to arterioles from WT rats (WT vs Nrf2 KO; P=0.054). Exercise training increased responsiveness to Dea‐NONO‐ate in arterioles from WT rats (WT EX vs WT SED; P<0.05), but not in arterioles from Nrf2KO rats. These data suggest that deficiency of Nrf2 alters the function of vascular smooth muscle, but not the function of the vascular endothelium in coronary arterioles. Exercise training increases the vasodilatory responsiveness of coronary arteriolar smooth muscle to nitric oxide, but not in the absence of Nrf2, suggesting that mechanisms of redox homeostasis and nitric oxide signaling interact in the smooth muscle of coronary arterioles.Support or Funding InformationNIH R15AG055029This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.