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INTEGRATIVE |
1 The Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, Denmark
2 Centre for Sports Medicine and Human Performance, Brunel University, Uxbridge, Middlesex, UK
3 Institute of Exercise and Sports Sciences, University of Copenhagen, Copenhagen, Denmark
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 and 
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 µg min–1), Indo +
NG-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 O2 delivery, cardiac output, heart rate and plasma [noradrenaline] (P < 0.05), while blood pressure remained unchanged and O2 extraction and femoral venous plasma [ATP] increased. Despite the increased O2 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.
(Received 22 December 2006;
accepted after revision 1 March 2007;
first published online 8 March 2007)
Corresponding author S. P. Mortensen: The Copenhagen Muscle Research Centre, Rigshospitalet, Section 7652, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Email stefan{at}sport.dk
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