title: Inhibition of nitric oxide synthesis by systemic N(G)-monomethyl-L-arginine administration in humans: effects on interstitial adenosine, prostacyclin and potassium concentrations in resting and contracting skeletal muscle.
abstract: We examined whether the formation or the release of the vasodilators adenosine, prostacyclin (PGI(2)) and potassium (K(+)) increase in skeletal muscle interstitium in response to nitric oxide synthase (NOS) inhibition. Five subjects 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 rest, during exercise and after exercise with the microdialysis technique. Interstitial adenosine in controls increased (p<0.05) from 0.11+/-0.03 micromol/l at rest to 0.48 +/-0.06 micromol/l during exercise. Interstitial adenosine during exercise in L-NAME was similar (p>0.05) to controls. The 6-keto-prostaglandin F1alpha concentration in controls was 1.17+/-0.20 ng/ml at rest and increased (p<0.05) to 1.97+/-0.30 ng/ml during exercise and was further elevated (p<0.05) to 2.76+/-0.38 ng/ml after exercise and these concentrations were not different (p>0.05) in L-NAME. The interstitial K(+) concentration in controls increased (p< 0.05) from 4.1+/-0.1 mmol/l at rest to 9.5+/-0.5 mmol/l during exercise. The interstitial K(+) concentration during exercise (6.7+/- 0.4 mmol/l) was lower (p<0.05) in L-NAME than in controls. The present findings demonstrate that the muscle interstitial concentrations of adenosine, PGI(2) and K(+) during exercise are not increased with systemic NOS inhibition. Thus, the lack of effect of NOS inhibition on the rate of blood flow to contracting human skeletal muscle does not appear to be due to compensatory formation or release of adenosine, PGI(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.
authors.affiliation: Copenhagen Muscle Research Centre, University of Copenhagen, Denmark.
authors.forename: U
authors.initials: U
authors.lastname: Frandsen
authors.forename: J
authors.initials: J
authors.lastname: Bangsbo
authors.forename: H
authors.initials: H
authors.lastname: Langberg
authors.forename: B
authors.initials: B
authors.lastname: Saltin
authors.forename: Y
authors.initials: Y
authors.lastname: Hellsten
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007866:Leg / Q000098:blood supply; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D012146:Rest; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000241:Adenosine; D011188:Potassium