Journal of Applied Physiology
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J Appl Physiol 92: 461-468, 2002; doi:10.1152/japplphysiol.01152.2000
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Vol. 92, Issue 2, 461-468, February 2002

Endothelial modulation of skeletal muscle blood flow and VO2 during low- and high-intensity contractions

Cheryl E. King-VanVlack1,2, J. D. Mewburn2, C. K. Chapler2, and P. H. MacDonald3

1 School of Rehabilitation Therapy, 2 Department of Physiology, and 3 Department of Surgery, Queen's University, Kingston, Ontario, Canada K7L 3N6

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 O2 uptake (VO2) would be affected by the decrease in muscle Q with NOS inhibition at different contraction intensities. Muscle Q, VO2, O2 extraction ratio (OER), and tension development (TD) were studied in the in situ gastrocnemius muscle preparation in anesthetized dogs. A decrease in the VO2-to-TD ratio (VO2/TD) was used as an indicator of O2 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 ETA-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 (Nomega -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 ETA-receptor blockade. In both groups, OER increased in response to the fall in Q, with the result being no change in VO2/TD. NOS inhibition also decreased Q during 4 tw/s contractions, but OER did not increase, resulting in a reduction in VO2/TD 5 and 15 min after Nomega -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 O2 limitation or an alteration in the efficiency of muscle contractions.

fatigue; oxygen extraction; tension development; oxygen demand


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