title: Inhibition of nitric oxide and prostaglandins, but not endothelial-derived hyperpolarizing factors, reduces blood flow and aerobic energy turnover in the exercising human leg.
abstract: Prostaglandins, nitric oxide (NO) and endothelial-derived hyperpolarizing factors (EDHFs) are substances that have been proposed to be involved in the regulation of skeletal muscle blood flow during physical activity. We measured haemodynamics, plasma ATP at rest and during one-legged knee-extensor exercise (19 +/- 1 W) in nine healthy subjects with and without intra-arterial infusion of indomethacin (Indo; 621 +/- 17 microg min(-1)), Indo + N(G)-monomethyl-L-arginine (L-NMMA; 12.4 +/- 0.3 mg min(-1)) (double blockade) and Indo + L-NMMA + tetraethylammonium chloride (TEA; 12.4 +/- 0.3 mg min(-1)) (triple blockade). Double and triple blockade lowered leg blood flow (LBF) at rest (P<0.05), while it remained unchanged with Indo. During exercise, LBF and vascular conductance were 2.54 +/- 0.10 l min(-1) and 25 +/- 1 mmHg, respectively, in control and they were lower with double (33 +/- 3 and 36 +/- 4%, respectively) and triple (26 +/- 4 and 28 +/- 3%, respectively) blockade (P<0.05), while there was no difference with Indo. The lower LBF and vascular conductance with double and triple blockade occurred in parallel with a lower O(2) delivery, cardiac output, heart rate and plasma [noradrenaline] (P<0.05), while blood pressure remained unchanged and O(2) extraction and femoral venous plasma [ATP] increased. Despite the increased O(2) extraction, leg was 13 and 17% (triple and double blockade, respectively) lower than control in parallel to a lower femoral venous temperature and lactate release (P<0.05). These results suggest that NO and prostaglandins play important roles in skeletal muscle blood flow regulation during moderate intensity exercise and that EDHFs do not compensate for the impaired formation of NO and prostaglandins. Moreover, inhibition of NO and prostaglandin formation is associated with a lower aerobic energy turnover and increased concentration of vasoactive ATP in plasma.
authors.affiliation: The Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, Denmark. stefan@sport.dk
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Mortensen
authors.forename: José
authors.initials: J
authors.lastname: González-Alonso
authors.forename: Rasmus
authors.initials: R
authors.lastname: Damsgaard
authors.forename: Bengt
authors.initials: B
authors.lastname: Saltin
authors.forename: Ylva
authors.initials: Y
authors.lastname: Hellsten
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D001685:Biological Factors / Q000378:metabolism*; D001783:Blood Flow Velocity; D002302:Cardiac Output; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015444:Exercise; D006339:Heart Rate; D006801:Humans; D006940:Hyperemia / Q000378:metabolism / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D007866:Leg; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010101:Oxygen Consumption; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D012039:Regional Blood Flow; D019789:Tetraethylammonium / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D011453:Prostaglandins; C067410:endothelium-dependent hyperpolarization factor; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D007213:Indomethacin