Aging alters the contribution of nitric oxide to regional muscle hemodynamic control at rest and during exercise in rats

Hirai DM, Copp SW, Hageman KS, Poole DC, Musch TI. Aging alters the contribution of nitric oxide to regional muscle hemodynamic control at rest and during exercise in rats. J Appl Physiol 111: 989-998, 2011. First published July 14, 2011; doi:10.1152/japplphysiol.00490.2011.-Advanced age is associated with altered skeletal muscle hemodynamic control during the transition from rest to exercise. This study investigated the effects of aging on the functional role of nitric oxide (NO) in regulating total, inter-, and intramuscular hindlimb hemodynamic control at rest and during submaximal whole body exercise. We tested the hypothesis that NO synthase inhibition (N-G-nitro-L-arginine methyl ester, L-NAME; 10 mg/kg) would result in attenuated reductions in vascular conductance (VC) primarily in oxidative muscles in old compared with young rats. Total and regional hindlimb muscle VCs were determined via radiolabeled microspheres at rest and during treadmill running (20 m/min, 5% grade) in nine young (6-8 mo) and seven old (27-29 mo) male Fisher 344 x Brown Norway rats. At rest, L-NAME increased mean arterial pressure (MAP) significantly by similar to 17% and 21% in young and old rats, respectively. During exercise, L-NAME increased MAP significantly by similar to 13% and 19% in young and old rats, respectively. Compared with young rats, L-NAME administration in old rats evoked attenuated reductions in 1) total hindlimb VC during exercise (i.e., down by similar to 23% in old vs. 43% in young rats; P < 0.05), and 2) VC in predominantly oxidative muscles both at rest and during exercise (P < 0.05). Our results indicate that the dependency of highly oxidative muscles on NO-mediated vasodilation is markedly diminished, and therefore mechanisms other than NO-mediated vasodilation control the bulk of the increase in skeletal muscle VC during the transition from rest to exercise in old rats. Reduced NO contribution to vasomotor control with advanced age is associated with blood flow redistribution from highly oxidative to glycolytic muscles during exercise.