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

摘要

Please cite this paper as: Copp, Hirai, Ferguson, Musch and Poole (2011). Role of Neuronal Nitric Oxide Synthase in Modulating Microvascular and Contractile Function in Rat Skeletal Muscle. Microcirculation 18(6), 501-511. 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(2) mv) 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(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 2.1 mumol/kg of the selective nNOS inhibitor SMTC. Results: At rest, spinotrapezius blood flow was not different whereas SMTC reduced ( downward arrow27%) resulting in an elevated precontracting baseline Po(2) mv (control: 31.2 +/- 1.6, SMTC: 37.1 +/- 2.0 mmHg, 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 +/- 1.4 seconds, p < 0.05). During the contracting steady-state, SMTC reduced spinotrapezius blood flow ( downward arrow17%) and ( downward arrow17%) such that Po(2) mv was not different (control: 22.8 +/- 1.6, SMTC: 22.7 +/- 2.1 mmHg, p > 0.05) which occurred despite an elevated ( upward arrow approximately 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.