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 adenosin e. We determined the effects of adenosine, GTN and their combination o n platelet responses in platelet-rich plasma and whole blood, and on i ntracellular levels of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP). 2. Adenosine inhibited t he 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 dur ing myocardial ischaemia or haemorrhagic shock. 3. GTN was able to dec rease platelet responses influencing intraplatelet cGMP levels. Furthe rmore, the drug increased the inhibitory effects of adenosine and enha nced its effects on intraplatelet cAMP levels. 4. The present data pro vides further evidence that compounds that increase intraplatelet leve ls of cGMP and cAMP act synergistically on the inhibition of platelet aggregability through the influence of increased cGMP levels on cAMP a ccumulation, 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 l evels are significantly increased.