Interactions between endogenous nitric oxide and hypoxemia in activation of group IV muscle afferents

It has previously been shown that both hypoxemia and nitric oxide (NO) synthase blockade depress the activation of group IV muscle afferents after muscle stimulation (MS). In the present study, we questioned whether hypoxemia exerts a specific inhibitory influence, independently from its effects on endogenous NO formation. This hypothesis was tested in two groups of anesthetized rabbits in which we examined the effects of hypoxemia, and then of subsequent NO synthase blockade by N(G)-nitro-L-arginine methyl ester (L-NAME), and vice versa. In each protocol, group IV afferent activity was recorded from the resting tibialis anterior muscle and after 3-min periods of MS that elicited a significant decrease in muscle force. NO synthase blockade in normoxemia suppressed the group IV afferent response to MS, and hypoxemia alone significantly reduced the post-MS activation of these nerve afferents (+18% vs. +28% in normoxemia). In hypoxemic rabbits, further NO synthase blockade abolished the post-MS activation of group IV afferents. Moreover, when hypoxemia followed the NO synthase blockade, MS significantly reduced the discharge of group IV afferents (-28%). Thus, while these muscle afferents are activated after fatiguing muscle contractions when the endogenous NO production is present, they are deactivated by hypoxemia when NO production is blocked. We conclude that endogenous NO production and hypoxemia exert opposite effects on the activation of the group IV afferents. Our data anticipate the neuromuscular side effects of treatments using exogenous NO or drugs acting on endogenous NO production.