Introduction
Whereas adenosine previously has been found of importance for regulating skeletal muscle exercise hyperaemia in cats (Poucher et al. 1990) evidence in humans are lacking. The interstitial concentration of adenosine in skeletal muscle of humans was, however, recently found to increase in direct relation to the magnitude of blood flow response during exercise (Hellsten et al. 1998). Our aim was therefore to directly investigate the role of adenosine in exercise induced skeletal muscle vasodilatation in humans by evaluating the effect of adenosine receptor blockade with theophylline.
Methods
Six human subjects performed one-legged dynamic knee extension exercise prior to and after i.v. theophylline infusion (6.9 mg/kg body weight). Catheters were placed in the femoral artery and vein for blood sampling and arterial blood pressure measurement. Femoral artery blood flow (FaBF) was measured by ultrasound Doppler (Rådegran 1997). The experiments were approved by the Ethical Committees of Copenhagen and Fredriksberg. The values are mean +- SE.
Results
At rest, theophylline increased (p < 0.05) femoral artery blood flow (FaBF) from 0.23 +- 0.034 to 0.57 +- 0.15 l·min-1 and vascular conductance (VC) from 2.5 +- 0.3 to 6.3 +- 1.8 ml·min-1·mmHg-1, whereas limb oxygen uptake and lactate release remained unaltered (p = ns). During exercise at 33 W (~ 46 % of peak power output), theophylline decreased (p < 0.003) FaBF by ~ 19 %, i.e. from 3.56 +- 0.48 to 2.90 +- 0.46 l·min-1, and VC from 33.4 +- 9.1 to 27.7 +- 8.5 ml·min-1·mmHg-1, whereas limb oxygen uptake and lactate release remained unaltered (p = ns).
Conclusions
If accounting during exercise for the theophylline induced secondary "background" vasodilatation observed at rest, it can be assumed that the sum of the counteracting FaBF increase at rest and decrease during exercise more resembles an actual decrease in exercise hyperaemia of ~ 26 +- 3 %. Moreover, knowing that theophylline is a non-selective adenosine receptor blocker, also lacking a 100 % efficiency, and since redundant mechanisms may partially compensate for a theophylline induced reduction of blood flow during exercise, the present data suggest that adenosine may control more than ~ 1/5 - 1/4 of the hyperaemic response to sub-maximal exercise in skeletal muscle of humans.
References
Hellsten, Y., MacLean, D.M., Rådegran, G., Saltin, B. & Bangsbo, J. 1998. Circulation 98, 6-8.
Poucher, S.M., Nowell, C.G. & Collis, M.G. 1990. J. Physiol. 427, 19-29.
Rådegran, G. 1997. J. Appl. Physiol. 83, 1383-1388.