Anti-aggregatory effects of physiological concentrations of adenosine in human whole blood as assessed by filtragometry.
1. The anti-aggregatory effect of adenosine (0.3-10 mumol/l), alone or in combination with the adenosine-uptake inhibitor dipyridamole (2 mumol/l), was studied in vitro in whole blood from 11 healthy subjects by filtragometry. 2. ADP (0.05-0.1 mumol/l) was used to reduce the filter occlusion time (tA, a measure of platelet aggregate formation in blood) from approximately 600 s to 71-101 s in the absence of other agents. 3. Adenosine was infused into the tubing system of the filtragometer, yielding a contact time of approximately 25 s with the blood before the filter. Adenosine did not influence the aggregatory response to ADP significantly at 0.3 mumol/l in plasma, whereas tA was prolonged by 19 +/- 6% (P less than 0.02) at 1 mumol/l adenosine and by 259 +/- 78% (P less than 0.02) at 3 mumol/l adenosine. 4. When the rapid elimination of adenosine from plasma was prevented by 2 mumol/l dipyridamole, adenosine caused marked prolongation of ADP-induced tA, with significant effects at 0.3 mumol/l (+143 +/- 72%, P less than 0.05). Dipyridamole per se did not affect tA values. 5. The present results suggest that adenosine has a transient anti-aggregatory effect in whole blood at about 0.3 mumol/l, as this is the highest possible calculated concentration of adenosine at the filter of the apparatus when 1 mumol/l adenosine is infused in the absence of dipyridamole or when 0.3 mumol/l adenosine is infused in its presence. 6. It is concluded that adenosine has anti-aggregatory effects at submicromolar (physiological) concentrations in human whole blood.(ABSTRACT TRUNCATED AT 250 WORDS)
Söderbäck
U
U
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Sollevi
A
A
Wallen
N H
NH
Larsson
P T
PT
Hjemdahl
P
P
D000241:Adenosine / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D005374:Filtration / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D004176:Dipyridamole; D000241:Adenosine