Presentation description

N-Acetyl-Carnosine (NAC), a derivative of carnosine, is an endogenous antioxidant. Earlier our laboratory group (Eshima et al., Elife, 2023) reported that 7-days of hindlimb-unloading in older mice treated with vehicle elevated skeletal muscle 4-hydroxy-2-nonenal expression and atrophy, while reducing ex vivo pulse-stimulated skeletal muscle force-generation. Of note, each effect was attenuated in hindlimb-unloaded, older mice treated with NAC. Improved blood supply to hindlimb-unloaded muscle secondary to heightened endothelial function has potential to lessen the detrimental impact of this maneuver on oxidative stress, muscle size, and function. Here we tested the hypothesis that endothelial dysfunction is less severe in older mice supplemented with NAC vs. vehicle. Sixteen-month-old female mice consumed standard chow + (i) tap water (CON, n=6) or (ii) tap-water supplemented with 80 mM NAC (NAC, n=8) for 6-months. At 24-months, femoral and middle cerebral arteries (MCAs) were obtained to assess vascular reactivity using isometric and isobaric procedures, respectively. First, NAC (mass spectrometry) was higher in muscle obtained from NAC vs. CON mice. Next, in contrast to our hypothesis, acetylcholine-evoked vasorelaxation in femoral arteries or MCAs was not different between NAC and CON mice. In the presence of the non-selective nitric oxide synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA), acetylcholine-evoked vasorelaxation was attenuated to a greater extent in NAC vs. CON mice, for both femoral and MCAs. These data suggest that vascular nitric oxide bioavailability is greater in NAC vs. CON mice, and might contribute to attenuating skeletal muscle oxidative damage and atrophy, and improving skeletal muscle force generation, in older mice upon hindlimb-unloading.