Summary
In a placebo-controlled double blind cross-over experiment the adenosine uptake inhibitor
dipyridamole (400 mg/day) did not affect ex vivo platelet aggregation induced by collagen
or adenosine-diphosphate (ADP) in an electronic whole blood aggregometer (WBA). Dipyridamole
was also inactive in vitro, unless red blood cell injury was deliberately enhanced,
thereby increasing the level of free adenine nucleotides. Since dipyridamole also
inhibits cyclic guanosine monophosphate (GMP) phosphodiesterase (PDE), we used platelet
rich plasma (PRP) to study its interaction with authentic and endothelium-derived
nitric oxide (NO). The latter inhibits platelets by increasing cyclic GMP. Dipyridamole
(1 to 30 εM), either alone or in combination with a subthreshold concentration of
prostacyclin (PGI2), was inactive. However, when combined with a subthreshold concentration of NO, dipyridamole
caused a concentration-dependent platelet suppression, which became more pronounced
when PGI2 was present as well. It is concluded that dipyridamole could reduce the threshold
for platelet suppression by NO through inhibition of cyclic GMP PDE.
