Effects of neuronal nitric oxide synthase (nNOS) inhibition on microvascular O 2 pressures during contractions in rat skeletal muscle

The role of nNOS‐derived NO in setting the dynamic balance between skeletal muscle microvascular O 2 delivery/utilization (which sets the driving pressure for blood‐myocyte O 2 flux, microvascular PO 2 ) during contractions is unknown. Objective To test the hypothesis that nNOS inhibition (S‐methyl‐L‐thiocitrulline, SMTC) would reduce muscle microvascular PO 2 at rest and during contractions. Methods Microvascular PO 2 (phosphorescence quenching) was measured in the spinotrapezius muscle of 10 male Sprague‐Dawley rats at rest and during 3 minutes of electrically‐induced twitch contractions (1 Hz, 6–8 v) before (CON) and after SMTC (2.1 μmol/kg i.a.). Significance was set at P < 0.05. Results Resting microvascular PO 2 was increased (CON: 31.2 ± 1.8, SMTC: 37.1 ± 2.2 mmHg). During contractions, SMTC reduced the time delay (CON: 8.2 ± 0.9, SMTC: 5.1 ± 0.7 s) and increased the amplitude (CON: 8.4 ± 0.5, SMTC: 14.7 ± 1.6 mmHg) of the dynamic response resulting in a similar steady‐state microvascular PO 2 (CON: 22.8 ± 1.8, SMTC: 22.7 ± 2.4 mmHg). SMTC sped the time to reach 63% of the rest‐contractions response (CON: 23 ± 1, SMTC: 17 ± 1 s). Conclusion nNOS‐derived NO plays a critical role in setting the O 2 delivery/utilization balance (i.e., microvascular PO 2 ) in rat skeletal muscle. This identifies nNOS as a putative mediator of age and disease‐induced reductions of NO bioavailability. Funding: KSU SMILE and AHA.