Role of neuronal nitric oxide synthase in modulating microvascular and contractile function in rat skeletal muscle

This investigation tested the hypothesis that selective nNOS inhibition would lower the dynamic microvascular O2 delivery/utilization () balance (which sets the Po(2) mv) in rat skeletal muscle at rest and during contractions.

Anesthetized male Sprague-Dawley rats had their spinotrapezius muscles exposed for blood flow (radiolabeled microspheres), (direct Fick calculation), Po(2) mv (phosphorescence quenching), or exteriorized for force production measurement during electrically induced contractions (1 Hz, 6-8 V, 180 seconds) pre- and post-nNOS inhibition with 2.1μmol/kg of the selective nNOS inhibitor SMTC.

At rest, spinotrapezius blood flow was not different whereas SMTC reduced (↓27%) resulting in an elevated precontracting baseline Po(2) mv (control: 31.2±1.6, SMTC: 37.1±2.0mmHg, p<0.05). Following contractions onset SMTC speeded the time to reach 63% of the overall Po(2) mv kinetics response (control: 22.5 ± 1.6, SMTC: 16.9±1.4seconds, p<0.05). During the contracting steady-state, SMTC reduced spinotrapezius blood flow (↓17%) and (↓17%) such that Po(2) mv was not different (control: 22.8±1.6, SMTC: 22.7±2.1mmHg, p>0.05) which occurred despite an elevated (↑∼8%) muscle force production.

These data demonstrate important physiological roles for nNOS-derived NO during contractions in healthy rat skeletal muscle and implicate maladaptations in nNOS function in pathological conditions associated with reduced NO bioavailability.