Venous but not skeletal muscle interstitial nitric oxide is increased during hypobaric hypoxia

Systemic hypoxia leads to peripheral vasodilation that serves to counteract the decrease in peripheral oxygen (O2) delivery. Skeletal muscle vasodilation associated with hypoxia is due to release of vasodilator substances such as adenosine and/or nitric oxide (NO). We hypothesized that skeletal muscle may act as a source of NO during exposure to hypoxia. Therefore, we measured NO in forearm venous plasma and in skeletal muscle interstitial dialysate in seven healthy young men during exposure to simulated altitude of 2,438 and 4,877 m (20 min at each level) in a hypobaric chamber. O2 saturation (mean ± SEM) fell from 98.0 ± 0.2% at ambient conditions to 91.0 ± 0.4% at 2,438 m and to 73.2 ± 4.4% at 4,877 m (P < 0.05). While blood pressure remained unchanged, heart rate increased in a graded fashion (P < 0.05). Plasma NO (chemiluminescence method) rose from 11.6 ± 1.3 to 16.9 ± 2.9 μM at 2,438 m (P < 0.05) but remained similar at 16.4 ± 2.3 μM at 4,877 m (NS). In contrast, skeletal muscle microdialysate NO levels were lower than plasma NO (P < 0.01) and did not change during simulated altitude. Thus, hypoxia produced by simulated high altitude exposure leads to an increase in plasma but not skeletal muscle interstitial NO. These data support an important role of NO in the peripheral vascular responses to hypoxia. The differential responses of plasma vs. interstitial NO during hypoxia suggest an endothelial or intravascular source of NO.