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

Abstract

Objective: This investigation tested the hypothesis that selective nNOS inhibition would lower the dynamic microvascular O 2 delivery/utilization () balance (which sets the Po 2mv) in rat skeletal muscle at rest and during contractions. Methods: Anesthetized male Sprague-Dawley rats had their spinotrapezius muscles exposed for blood flow (radiolabeled microspheres), (direct Fick calculation), Po 2mv (phosphorescence quenching), or exteriorized for force production measurement during electrically induced contractions (1Hz, 6-8V, 180seconds) pre- and post-nNOS inhibition with 2.1μmol/kg of the selective nNOS inhibitor SMTC. Results: At rest, spinotrapezius blood flow was not different whereas SMTC reduced (↓27%) resulting in an elevated precontracting baseline Po 2mv (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 2mv 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 2mv 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. Conclusions: 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. © 2011 John Wiley & Sons Ltd.