Differential antagonism of cardiac actions of adenosine by theophylline.
OBJECTIVE
To determine the relative sensitivity of cardiac A1- and A2-adenosine receptor-mediated effects to antagonism by theophylline in man.


METHODS
Baseline measurements of the A-H interval (A1-adenosine receptor-mediated effect) and coronary blood flow (A2-adenosine receptor-mediated effect) were made in 10 patients with angiographically normal coronary arteries. Adenosine was then administered as a continuous intravenous infusion followed by a rapid intravenous bolus, and measurements repeated. Theophylline (5 mg/kg i.v.) was then administered, and the adenosine infusion repeated. To corroborate the results found in man, the cardiac A1- and A2-adenosine receptor-mediated effects were measured in guinea pig isolated hearts exposed to increasing concentrations of adenosine, in the absence and presence of theophylline (60 microM).


RESULTS
Compared to baseline, adenosine infusion and bolus caused significant prolongation of the A-H interval (109 +/- 41 vs. 116 +/- 44 vs. 168 +/- 57 ms, respectively), and increase in coronary blood flow (46 +/- 37 vs. 86 +/- 71 vs. 172 +/- 98 ml/min, respectively). Theophylline abolished the prolongation of the A-H interval during adenosine infusion and bolus (99 +/- 36 and 107 +/- 44 ms, respectively), yet had minimal effect on the increase in coronary blood flow (63 +/- 51 and 136 +/- 121 ml/min, respectively). In guinea pig isolated hearts, theophylline was shown to significantly antagonize the A2-adenosine receptor-mediated effects only when the concentrations of adenosine were < or = 1.0 microM.


CONCLUSIONS
In man, theophylline completely antagonizes the A1-adenosine receptor-mediated prolongation of the A-H interval, but has minimal effect on the A2-receptor-mediated coronary vasodilation, particularly when adenosine concentrations exceed 1.0 microM.
Bertolet
B D
BD
Department of Medicine, University of Florida Health Sciences Center, Gainesvilla 32610-0277, USA.
Belardinelli
L
L
Avasarala
K
K
Calhoun
W B
WB
Franco
E A
EA
Nichols
W W
WW
Kerensky
R A
RA
Hill
J A
JA
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000818:Animals; D001667:Binding, Competitive; D003326:Coronary Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D011983:Receptors, Purinergic / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D013806:Theophylline; D000241:Adenosine