Endogenous nitric oxide in the control of skeletal muscle oxygen extraction during exercise

Our previous studies uncovered an inhibitory effect of nitric oxide (NO) on leg skeletal muscle respiration in dogs at rest. The role of NO in the mod ulation of O-2 consumption and O-2 extraction in hindlimb muscle during ele vated metabolic states was investigated in chronically instrumented dogs wh ile walking and at three exercise intensities which markedly increased hind limb blood flow. Walking resulted in increased O-2 consumption by 17 +/- 4 mL min(-1) and O-2 extraction from 24 +/- 1 to 37 +/- 8%, with no alteratio n in hindlimb blood flow (BFLeg) and vascular resistance (VRLeg). Running a t the highest speed (9.1 mph) resulted in an increase in BFLeg from 0.67 +/ - 0.05 to 2.2 +/- 0.1 L min(-1), a reduction of VRLeg and elevation of hind limb O-2 consumption from 33 +/- 3 to 226 +/- 21 mL min(-1) and O-2 extract ion from 29 +/- 2 to 61 +/- 5%, with a decrease in leg venous PO2 from 38 /- 1 to 25 +/- 1 mmHg. After nitro-L-arginine (NLA) (35 mg kg(-1), i.v.) to inhibit endogenous NO synthesis, walking caused greater increases in hindl imb O-2 consumption (29 +/- 5 mL min(-1)) and O-2 extraction (43 +/- 1 to 6 0 +/- 3%) (both P < 0.05), with no significant change in BFLeg. During runn ing at the highest speed, BFLeg was 1.9 +/- 0.1 L min(-1) (P < 0.05) and VR Leg was higher, accompanied by increases in hindlimb O-2 consumption from 4 9 +/- 7 to 318 +/- 24 mL min(-1) and O-2 extraction from 41 +/- 2 to 79 +/- 4% (both P < 0.05), with a greater decrease in leg venous PO2 from 33 +/- 1 to 20 +/- 1 mmHg (P < 0.05). Similar results were found for intermediate levels of exercise. Our results indicate that NO modulates hindlimb skeleta l muscle O-2 extraction and O-2 usage whether blood flow increased or not d uring exercise.