Aerobic exercise increases stress resistance in arteries of old mice (1106.9)

Impaired ability of the aging vasculature to respond to stress may contribute to endothelial dysfunction, assessed as reduced endothelium‐dependent dilation (EDD). Mitochondrial (mito) dysregulation (e.g., excess mito reactive oxygen species (mtROS) production) with aging may increase susceptibility to stress. Aerobic exercise improves endothelial function with advancing age, but whether exercise affects vascular stress resistance is unknown. Max carotid EDD to acetylcholine (ACh) was reduced in old (O, n=7; 26‐28 mo) versus young (Y, n=7; 6‐8 mo) c57 mice (74 ±5% vs. 94 ±2%, p<0.05), but restored in old mice with 12 weeks access to voluntary run wheels (OVR, n=8; 89 ±3%, p<0.05 vs. O). Inducing mtROS with rotenone (0.5 µM, 40’ incubation) further impaired EDD in O (‐44 ±8%, p<0.05 vs. ACh alone), but not Y and OVR (‐7 ±2% and ‐3 ±15%). Incubating arteries with a simulated “Western” diet (sWD: 80 mM glucose, 300 µM palmitate, 40’) reduced max EDD in both O and Y (‐26 ±4% and ‐28 ±5% vs. ACh alone, both p<0.05), but OVR were resistant (‐6 ±5%). Simultaneous incubation with mito‐specific antioxidant MitoQ prevented sWD‐induced impairments, indicating mtROS mediation. Increased stress resistance in OVR was accompanied by amelioration of age‐related increases in aortic mito‐specific superoxide production (EPR; O: 1.5 ±0.4, p<0.05 vs. Y: 1.0 ±0.3 and OVR: 0.9 ±0.4 AU) and expression of phosphorylated (activated) adaptor protein p66 SHC (Western blot; O: 11.3 ±6.1, p<0.05 vs. Y: 1.0 ±0.6 and OVR: 2.5 ±2.6 AU), a master mtROS regulator. Our results suggest that aerobic exercise increases resistance to acute stress in aging arteries, possibly via favorable changes in vascular mito oxidative stress and homeostasis.