Glyceryl trinitrate enhances the adenosine-induced inhibition of platelet responses: a mechanism potentially involved in the in vivo anti-aggregating effects of organic nitrates.
1. The present study investigated the influence of the organic nitrate glyceryl trinitrate (GTN) on the anti-aggregating effects of adenosine. We determined the effects of adenosine, GTN and their combination on platelet responses in platelet-rich plasma and whole blood, and on intracellular levels of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP). 2. Adenosine inhibited the in vitro platelet aggregation in response to different agonists in a dose-dependent way through an elevation of intraplatelet cAMP levels. Effective adenosine concentrations were higher than those detectable under physiological conditions, but very close to levels achieved during myocardial ischaemia or haemorrhagic shock. 3. GTN was able to decrease platelet responses influencing intraplatelet cGMP levels. Furthermore, the drug increased the inhibitory effects of adenosine and enhanced its effects on intraplatelet cAMP levels. 4. The present data provides further evidence that compounds that increase intraplatelet levels of cGMP and cAMP act synergistically on the inhibition of platelet aggregability through the influence of increased cGMP levels on cAMP accumulation. The interplay between GTN and adenosine in the inhibition of platelet function could be effective during nitrate administration in the treatment of acute myocardial ischaemia when blood adenosine levels are significantly increased.
Anfossi
G
G
Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
Massucco
P
P
Piretto
V
V
Mularoni
E
E
Cavalot
F
F
Mattiello
L
L
Trovati
M
M
D000241:Adenosine / Q000494:pharmacology*; D000328:Adult; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D004176:Dipyridamole; D000242:Cyclic AMP; D005996:Nitroglycerin; D006152:Cyclic GMP; D000241:Adenosine