451 - Endogenous vs. Dietary Nitrate and Nitrite Distribution in Rat Skeletal Muscle during Exercise

Abstract

Nitric oxide (NO), small gaseous molecule generated enzymatically by a family of NOS enzymes, is a potent vasodilator. At low oxygen conditions, NO is generated in a series of nonenzymatic reactions from nitrite and nitrate. In the past decade, these two ions started to be considered as storage and precursors molecules for NO. We recently showed that skeletal muscle is the largest body reservoir of nitrate with levels 2-3 times higher than those found in blood or any other internal organ. We proposed that this endogenous nitrate serves as a precursor for NO in muscle during the exercise-induced hypoxia and following active hyperemia. It is known that dietary nitrate intake increases exercise endurance, even if the exact mechanism is still up to debate. In our study, using the combination of dietary nitrate manipulation and exercise, we try to understand relative roles of skeletal muscle endogenous nitrate and exogenous (dietary) nitrate at resting state and during exercise. We showed that the endogenous nitrate stored in skeletal muscle is extensively used by the whole body at times of low nitrate intake in both, resting and exercising state. Dietary nitrate excess is delivered by bloodstream mainly into liver (and likely into other internal organs), but only in very low extent into muscle tissue. However, when on excess of nitrate, nitrite drastically increased in all studied organs. We hypothesize that it is the nitrite, formed in liver from dietary nitrate excess that is transported into skeletal muscle during exercise where it improves performance. The mechanism by which exercise enhances the transport of nitrite derived from dietary sources into skeletal muscle is still unclear.