Exercise in the heat: effects of an adenosine antagonist

The purpose of this experiment was to examine the effects of an adenosine antagonist on cardiovascular, thermoregulatory, and exercise performance in the heat. Two doses (1 mg/kg and 10 mg/kg) of a selective adenosine A1 antagonist (1,3-di-n-propyl-8-[4-hydroxyphenyll]xanthine) (DPHPX) were tested in a rat model of exercise exhaustion, treadmill 11 m/min, 6 degrees incline, in the heat 30 degrees C. Pretreatment with the experimental adenosine antagonist caused a slight improvement p > 0.05 in run time (41+/-4 vs. 44+/-3 mm) at a low dose but reduced performance (41+/-4 vs. 29+/-3 mm) at a high dose despite elevated plasma lactate (6.41+/-0.82 vs. 9.91+/-1.0 and 12.42+/-1.1 micromole/L) levels in both dosage groups. At the low dose the antagonist provided a clear benefit in thermoregulation as evidenced by reduced heating rates (0.079+/-0.005 vs. 0.050+/-0.009 degrees C/min). Heart rate and blood pressure tended to be preserved in the low dose group also. Blood gases remained closer to normal with either dosage of drug with arterial PO2 being remarkably preserved after exercise whereas venous PO2 was not different suggesting increased oxygen delivery and extraction. The results of this investigation indicate that antagonizing the effects of adenosine at a low dose with this agent did improve cardiovascular and thermoregulatory responses but did not provide a substantial overall benefit in exercise performance in the heat.