Aminophylline and interstitial adenosine during sustained exercise hyperemia.

We tested the hypothesis that an increase in interstitial fluid (ISF) adenosine concentration contributes to vasodilation of high oxidative skeletal muscle during sustained free-flow exercise. Canine calf muscles were stimulated at 3 Hz for 10 min before and after the infusion of the adenosine receptor antagonist aminophylline (10 mg/kg). The vasodilation that occurred during aminophylline infusion was allowed to decay before the postaminophylline exercise period was begun. This dose of aminophylline shifted the response to infused adenosine 20-fold during rest and reduced the response to a standard dose by 90% during exercise. Aminophylline had no significant effect on blood flow or on O2 consumption at rest or during exercise. Adenosine release (venous minus arterial plasma concentration times plasma flow) increased during 3-Hz exercise both before and after aminophylline infusion, but venous plasma adenosine concentration did not increase in either case. We developed a mathematical model of adenosine movement between ISF and plasma to help us judge whether to use adenosine release or venous concentration as an index of ISF adenosine and decided that venous concentration should be used. We conclude that aminophylline has no effect on sustained 3-Hz exercise hyperemia because under these conditions ISF adenosine concentration does not increase.