Inhibition of nitric oxide synthesis by systemic N-G-monomethyl-L-arginineadministration in humans: Effects on interstitial adenosine, prostacyclin and potassium concentrations in resting and contracting skeletal muscle

We examined whether the formation or the release of the vasodilators adenos ine, prostacyclin (PGI(2)) and potassium (K+) increase in skeletal muscle i nterstitium in response to nitric oxide synthase (NOS) inhibition. Five sub jects performed one-legged knee extensor exercise at 30 W without (controls ) and with prior N-G-nitro-L-arginine methyl ester (L-NAME) infusion (4 mg/ kg, intravenously). Samples from the interstitial fluid were obtained at re st, during exercise and after exercise with the microdialysis technique. In terstitial adenosine in controls increased (p < 0.05) from 0.11 +/- 0.03 mu mol/l at rest to 0.48 +/- 0.06 mu mol/l during exercise. Interstitial aden osine during exercise in L-NAME was similar (p > 0.05) to controls. The 6-k eto-prostaglandin F1 alpha concentration in controls was 1.17 +/- 0.20 ng/m l at rest and increased (p < 0.05) to 1.97 +/- 0.30 ng/ml during exercise a nd was further elevated (p < 0.05) to 2.76 +/- 0.38 ng/ml after exercise an d these concentrations were not different (p > 0.05) in L-NAME. The interst itial K+ concentration in controls increased (p < 0.05) from 4.1 +/- 0.1 mm ol/l at rest to 9.5 +/- 0.5 mmol/l during exercise. The interstitial K+ con centration during exercise (6.7 +/- 0.4 mmol/l) was lower (p < 0.05) in L-N AME than in controls. The present findings demonstrate that the muscle inte rstitial concentrations of adenosine, PGI(2) and K+ during exercise are not increased with systemic NOS inhibition. Thus, the lack of effect of NOS in hibition on the rate of blood flow to contracting human skeletal muscle doe s not appear to be due to compensatory formation or release of adenosine, P GI(2) and K+ in the muscle interstitium. The present study also supports a role for PGI(2) in the regulation of blood flow during exercise. Copyright (C) 2000 S.Karger AG, Basel.