NITRIC-OXIDE SYNTHASE INHIBITORS DO NOT ALTER FUNCTIONAL HYPEREMIA INCANINE SKELETAL-MUSCLE

To test the hypothesis that endothelium-derived products contribute to functional hyperemia in skeletal muscle, we infused nitric oxide synt hase inhibitors, either 200 mu M N omega-nitro-L-arginine (NNA) (N = 4 ) or 1 mM N gamma-monomethyl-L-arginine (NMMA) (N = 4), before and dur ing 6 min of 4 Hz stimulation of canine gastrocnemius in situ. We infu sed saline (N = 4) as a control. NNA significantly decreased steady-le vel resting flow by 3.8 +/- 0.4 mL.kg(-1).s(-1). The increase in flow from rest to 5 min of stimulation was not changed by the nitric oxide synthase inhibitors. We also stimulated muscles for 60 min either with saline infusion (N = 4) or with the infusion of saline during the fir st 15 min and NNA for the remaining 45 min (N = 4). There was no diffe rence in the flow during contractions. To clarify the effect of these inhibitors on canine vessels, we challenged rings of canine femoral ar tery with and without endothelium with acetylcholine and bradykinin (b oth 1 mu M) before and after the addition of NNA and NMMA (both 10 mu M). The nitric oxide synthase inhibitors decreased the relaxation acco mpanying acetylcholine. Both inhibitors caused only endothelium-intact rings to contract. Thus, the presence of a nitric oxide synthase inhi bitor identified an endothelium-dependent contribution to the regulati on of blood flow to skeletal muscle at rest but had no effect on funct ional hyperemia.