Received July 26, 2005
Revised August 11, 2005
Accepted after revision August 23, 2005
NOS inhibition reduces the O2 cost of force development in rat hindlimb muscles pump perfused at matched convective O2 delivery
Daniel J Krause 1,
Jason L Hagen 1,
Casey A Kindig 2,
Russell T Hepple 1*
1 University of Calgary
2 University of California, San Diego
* To whom correspondence should be addressed. E-mail: hepple{at}ucalgary.ca.
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Abstract |
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Nitric oxide (NO) is a physiological mediator of skeletal muscle function. Specifically, NO affects cellular respiration and muscle contractility; however, reduced blood flow and convective O2 delivery related to impaired vasodilation observed with NO synthase (NOS) inhibition in vivo have obscured past interpretations of NO's effects. Therefore, we studied the effect of NOS inhibition in an in situ pump-perfused rat hindlimb to test the hypothesis that NOS inhibition would improve contractile and aerobic metabolic performance. Pump-perfusion permitted matching of convective O2 delivery (516±16 µmol O2.min-1.100g-1; mean ± SE) between groups allowing us to investigate the effects of NOS inhibition independent of this variable. Three groups were studied. The perfusate of one group was treated with both Adenosine (0.01 mM) and the NOS inhibitor, N
-nitro-L-arginine methyl ester (L-NAME; 1 mM). Adenosine is a vasodilator that can act both through NO-dependent and NO-independent pathways; adenosine's NO-independent vasodilatory action allowed for a similar perfusion rate and convective O2 delivery in the L-NAME group. The second group's perfusate was treated with Adenosine only (Ado). The third group's perfusate received no treatment and served as a control (Con). VO2 was on average 26% and 14% lower during the contraction bout in L-NAME and Ado, respectively, versus Con. Whereas lactate efflux was similar to Con and force was reduced in proportion to VO2 in Ado versus Con, L-NAME was associated with a 32% lower lactate efflux and similar force to Con. Therefore, the lower VO2/force development ratio in the L-NAME group demonstrates that the O2 cost of force development is reduced by NOS inhibition independent of convective O2 delivery.
Key Words:
L-NAME, Nitric oxide, Skeletal muscle
