Exercise-induced hyperaemia and leg oxygen uptake are not altered during effective inhibition of nitric oxide synthase with NG-nitro-L-arginine methyl ester in humans

1. In the present study the highly potent nitric oxide synthase (NOS) inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) was intravenously infused and examined for its efficacy in inhibiting NOS activity and in altering blood flow and oxygen uptake in human skeletal muscle. 2. The plasma concentrations of L-NAME and its active metabolite N-G-nitro-L-arginine (L-NA), and the activity of NOS in skeletal muscle were measured in healthy male subjects (n = 6) before (control) and after 60 min of intravenous infusion of L-NAME (4 mg kg(-1)). In another group of healthy males (n = 8), the physiological effects of L-NAME were studied at rest, and during submaximal and exhaustive knee extensor exercise before (control) and 30 min after L-NAME infusion (4 mg kg-l). 3. The plasma concentrations of L-NAME and L-NA were highest (8.4 +/- 1.6 and 8.3 +/- 0.8 mu mol l(-1)) after 60 min of L-NAME infusion. Ninety minutes later mainly L-NA remained in plasma (5.1 +/- 0.4 mu mol l(-1)). Thirty minutes after L-NAME infusion, the muscle L-NA content was 38 +/- 4 mu mol (kg dry wt)(-1) and muscle NOX activity was reduced by 67 +/- 8% (P < 0.05). 4. Leg blood flow and leg oxygen uptake during submaximal and exhaustive exercise were similar (P > 0.05) following L-NAME infusion and in control. Blood flow during recovery was lower in the L-NAME condition (P < 0.05). 5. In conclusion, the present study shows for the first time that systemic infusion of L-NAME in humans causes a marked reduction in skeletal muscle NOX activity. Despite this attenuated NOS activity, exercise-induced hyperaemia and oxygen uptake were unaltered. Thus, the data strongly suggest that NO is not essential for the regulation of blood flow or oxygen uptake in contracting human skeletal muscle.