Endothelial modulation of skeletal muscle blood flow andV˙ o 2 during low- and high-intensity contractions

In the present study, we determined whether endothelin (ET)-1 contributed to the observed reduction in muscle blood flow (Q˙) during contractions with nitric oxide synthase (NOS) inhibition and whether muscle O 2 uptake (V˙o 2 ) would be affected by the decrease in muscle Q˙ with NOS inhibition at different contraction intensities. Muscle Q˙,V˙o 2 , O 2 extraction ratio (OER), and tension development (TD) were studied in the in situ gastrocnemius muscle preparation in anesthetized dogs. A decrease in the V˙o 2 -to-TD ratio (V˙o 2 /TD) was used as an indicator of O 2 limitation. Three contraction protocols were used: 1) isometric twitch contractions at 2 twitches (tw)/s, 2) the same contractions at 4 tw/s, and 3) pretreatment with an ET A -receptor antagonist (BQ-123) before 2 tw/s contractions. The muscle was stimulated to contract, and measures were obtained at steady state (∼5–8 min). NOS inhibition ( N ω -nitro-l-arginine methyl ester) was then induced, and measures were repeated at 2, 5, 10, and 15 min. During 2 tw/s contractions, NOS inhibition reduced Q˙with and without ET A -receptor blockade. In both groups, OER increased in response to the fall in Q˙, with the result being no change in V˙o 2 /TD. NOS inhibition also decreased Q˙ during 4 tw/s contractions, but OER did not increase, resulting in a reduction inV˙o 2 /TD 5 and 15 min after N ω -nitro-l-arginine methyl ester. These data indicated that 1) a reciprocal increase in ET-1 during NOS inhibition does not influence active hyperemia in skeletal muscle, and 2) during 4 tw/s contractions, the ischemia with NOS inhibition was associated with either an O 2 limitation or an alteration in the efficiency of muscle contractions.