Experimental Physiology Nitric oxide synthase inhibition reduces the O2 cost of force development in rat hindlimb muscles pump perfused at matched convective O2 delivery

• Published in: Experimental physiology Vol. 90; no. 6; p. 889
• Main Authors: Krause, Daniel J, Hagen, Jason L, Kindig, Casey A, Hepple, Russell T
• Format: Journal Article
• Language: English
• Published: Oxford John Wiley & Sons, Inc 01-11-2005
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/expphysiol.2005.031567

Nitric oxide (NO) is a physiological mediator of skeletal muscle function. Specifically, NO affects cellular respiration and muscle contractility; however, the reduced blood flow and convective O2 delivery that result from impaired vasodilatation when NO synthase (NOS) is inhibited in vivo have obscured past interpretations of the effects of NO. 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 (100 g)-1; mean ± s.e.m.) 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 m m) and the NOS inhibitor, N ω-nitro-l-arginine methyl ester ( l-NAME; 1 m m). Adenosine is a vasodilator that can act through both NO-dependent and -independent pathways; the NO-independent vasodilatory action of adenosine allowed us to match the perfusion rate and convective O2 delivery in this l-NAME group to those of the other groups. In the second group the perfusate was treated with adenosine only (Ado). In the third group the perfusate received no treatment and served as a control (Con). Oxygen consumption was on average 26 and 14% lower during the contraction bout in l-NAME and Ado, respectively, versus Con. In Ado, lactate efflux was similar to Con and force was reduced in proportion to versus Con, whereas l-NAME was associated with a 32% lower lactate efflux and similar force to Con. Therefore, the lower :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.