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 °
incline, in the heat 30 ° 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 µmole/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 °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.
Key words:
Adenosine antagonist, cardiovascular, performance enhancement.
References
- 1
Armstrong L E, Maresh C M, Bergeron M F, Hoffman J R, Whittlesey M J, Roy G.
Exercise-heat tolerance of college distance runners at 38 NC.
J Strenth Cond Res.
1996;
10
190-196
- 2
Bacchus A N, Ely S W, Knabb M, Rubio R, Berne R M.
Adenosine and coronary blood flow in conscious dogs during normal physiological stimuli.
Am J Physiol.
1982;
243
H628-H633
- 3 Bellardinelli L, West A, Crampton R, Berne R M.
Chronotropic and dromotropic effects of adenosine. In: Berne RM, Rall TW, Rubio R (eds) Regulatory Function of Adenosine. Boston; Martinus
Niehoff 1983: 377-398
- 4
Belloni F L, Phair R D, Sparks X V.
The role of adenosine in prolonged vasodilation following flow-restricted exercise
of canine skeletal muscle.
Ciro Res.
1979;
44
759-766
- 5
Clarkson P M.
Nutrition for improved sports performance.
Sports Med.
1996;
21
393-401
- 6
Costill D L, Dalsky C, Fink W.
Effects of caffeine ingestion on metabolism and exercise performance.
Med Sci Sports.
1978;
10
155-158
- 7
De Garavilla L, Tocker J E, Valentine H L, Hanson R C.
A1-selective adenosine antagonists improve cardiovascular function during hemorrhagic
shock in rats.
Circ.
1987;
76
- 8
Drury A N, Szent-Cyorgi A.
The physiological activity of adenine compounds with special reference to their actions
upon the mammalian heart.
J Physiol London.
1929;
68
213-237
- 9
Durkot M J, de Garavilla L, Francesconi R.
The effects of dichloroacetate on lactate accumulation and endurance in an exercising
rat model.
Int J Sports Med.
1995;
16
167-171
- 10
Evans D B, Schenden A J, Bristol J A.
Adenosine receptors mediating cardiac depression.
Life Sci.
1982;
30
- 11
Fredholm B B, Sellevi A.
Cardiovascular effects of adenosine.
Clin Physiol.
1986;
6
1-21
- 12
Fuchs B D, Gorman M W, Sparks H V.
Adenosine release into venous plasma during free flow exercise.
Proc Soc Exp Biol Med.
1986;
181
364-370
- 13 Goodman A, Gilman L. The Pharmacological Basis of Therapeutics. MacMillan Publishing
Company Inc. 1980 6th Edition:
- 14
Hubbard R W, Matthew W T, Criss R EL, Kelly C, Sils I, Mager M, Bowers W D, Wolfe D.
Role of Physical effort in the etiology of rat heat injury and mortality.
J Appl Physiol.
1978;
45
463-468
- 15
Klabunde R E.
Conditions for dipyridamole potentiation of skeletal muscle active hyperemia.
Am J Physiol.
1986;
250
H62-H67
- 16
Lautt W W, Legare D J.
The use of 8-phenyltheophylline as competitive antagonist of adenosine and an inhibitor
of the intrinsic regulatory mechanism of the hepatic artery.
Can J Physiol Pharmacol.
1985;
63
717-722
- 17
Meester B J, Shankly N P, Welsh N J, Wood J, Meijler F I, Black J W.
Pharmacological classification of adenosine receptors in the sinoatrial and atrioventricular
nodes of the guinea pig.
Br J Pharmacol.
1998;
124
685-692
- 18
McKenzie J E, Steffen R P, Haddy F J.
Relationship between adenosine and coronary resistance in conscious exercising dogs.
Am J Physiol.
1982;
242
H24-H29
- 19 Barnhard E R. Physician Desk Reference. 6th Edition 1985
- 20
Proctor K G, Duling B R.
Adenosine and free-flow functional hyperemia in striated muscle.
Am J Physiol.
1982;
242
688-697
- 21 Reddington M, Lee K S. Adenosine receptor subtypes: classification and distribution.
Adenosine Nervous System. London, UK; Academic Press 1991: 77-102
- 22
Rowell L B, Brengelmann G L, Blackmon J R, Twiss R D, Kusumi F.
Splanchnic blood flow and metabolism in the heat-stressed man.
J Appl Physiol.
1968;
24
475-484
- 23 Sparks H V.
Skin and muscle. In: Johnson PC (ed) Peripheral Circulation. New York; Wiley 1978: 193-230
- 24
Spriet L L, MacLean D A, Dyck D J.
Caffeine ingestion and muscle metabolism during exercise in humans.
Am J Physiol.
1992;
262
891-898
Dr. M. J. Durkot
Military Nutrition and Biochemistry Division U.S. Army Research Institute of Environmental
Medicine
Kansas Street Natick, MA, 01760 USA
eMail: E-mail:michael.durkot@na.amedd.army.mil