Does a compensatory formation of nitric oxide during inhibition of prostanoid synthesis in skeletal muscle explain the redundancy between these vasoactive systems?

In skeletal muscle blood flow regulation a redundancy among vasodilators appear to exist, where a compensatory formation of one vasoactive compound may preserve adequate blood flow when the formation of another is compromised. To examine whether inhibition of prostanoid synthesis leads to a greater NO formation, skeletal muscle cells and skeletal muscle specific microvascular endothelial cells were treated with adenosine without and with inhibition of the enzyme cyclooxygenase to prevent prostanoid formation. The results showed that the adenosine‐induced formation of NO (as indicated by DAF‐FM fluorescence) was augmented (P<0.001) in microvascular endothelial cells (n=10) when the formation of prostanoids was inhibited, whereas no difference was detected in skeletal muscle cells (n=10). Samples from the interstitial fluid of human skeletal muscle obtained during exercise with the microdialysis technique will reveal to what extent inhibition of prostanoid synthesis leads to a compensatory formation of NO in vivo. These results indicate that an increase in NO formation in microvascular endothelial cells could compensate for a compromised prostanoid concentration in skeletal muscle.