Effects of neuronal nitric oxide synthase inhibition on microvascular and contractile function in skeletal muscle of aged rats.

Advanced age is associated with derangements in skeletal muscle microvascular function during the transition from rest to contractions. We tested the hypothesis that, contrary to what was reported previously in young rats, selective neuronal nitric oxide (NO) synthase (nNOS) inhibition would result in attenuated or absent alterations in skeletal muscle microvascular oxygenation (Po(2)(mv)), which reflects the matching between muscle O(2) delivery and utilization, following the onset of contractions in old rats. Spinotrapezius muscle blood flow (radiolabeled microspheres), Po(2)(mv) (phosphorescence quenching), O(2) utilization (Vo(2); Fick calculation), and submaximal force production were measured at rest and following the onset of contractions in anesthetized old male Fischer 344 × Brown Norway rats (27 to 28 mo) pre- and postselective nNOS inhibition (2.1 μmol/kg S-methyl-l-thiocitrulline; SMTC). At rest, SMTC had no effects on muscle blood flow (P > 0.05) but reduced Vo(2) by ∼23% (P < 0.05), which elevated basal Po(2)(mv) by ∼18% (P < 0.05). During contractions, steady-state muscle blood flow, Vo(2), Po(2)(mv), and force production were not altered after SMTC (P > 0.05 for all). The overall Po(2)(mv) dynamics following onset of contractions was also unaffected by SMTC (mean response time: pre, 19.7 ± 1.5; and post, 20.0 ± 2.0 s; P > 0.05). These results indicate that the locus of nNOS-derived NO control in skeletal muscle depends on age and metabolic rate (i.e., rest vs. contractions). Alterations in nNOS-mediated regulation of contracting skeletal muscle microvascular function with aging may contribute to poor exercise capacity in this population.