Evidence for isosorbide dinitrate (ISDN) promoting effect on prostacyclin release by the lung and prostacyclin implication in ISDN-induced inhibition of platelet aggregation in humans.
We investigated thromboxane B2 (TxB2), 6-keto-PGF1 alpha (6KPGF1 alpha reflecting prostacyclin), PGE2 and PGF2 alpha plasma levels; TxB2, PGE2 and PGF2 alpha platelet production and platelet aggregation response in ascending aorta (reflecting trans-pulmonary difference) and in venous coronary sinus (reflecting transcardiac difference) simultaneously in patients with ischemic heart disease, before and after right-atrial administration of 3 mg ISDN bolus. Transcardiac differences were scarce before as well as after ISDN administration. In aortic blood, ISDN administration into the right atria resulted in a significant increase in prostacyclin and PGF2 alpha plasma levels (472% and 242%, respectively), a decrease of both PGE2 plasma level (-173%) and PGE2 platelet production (-485%) and a marked lowering of platelet aggregation response to ADP, concomittantly. In contrast, TxB2-related features were poorly affected by ISDN. In coronary sinus blood, the aortic increase in 6KPGF1 alpha and PGF2 alpha plasma levels was detected to a lower extent whereas the characteristics of platelet aggregation had returned to control levels. By contrast, PGE2 plasma level (-191%) and PGE2 platelet production (-133%) were lower than prior ISDN administration. The results we report here, strongly support the view that ISDN promotes release of prostacyclin and PGF2 alpha from the lung and inhibit PGE2 production. These prostanoids may be responsible for the concomittant platelet reactivity lowering, thus providing a basis for understanding how ISDN might relieve myocardial ischemia favoring prostanoid mediated vasodilation and inhibition of platelet reactivity.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D003327:Coronary Disease / Q000097:blood; D015237:Dinoprost; D015232:Dinoprostone; D004537:Eicosanoic Acids / Q000097:blood; D011464:Epoprostenol / Q000097:blood*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D011458:Prostaglandins E / Q000097:blood; D011460:Prostaglandins F / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood
D004537:Eicosanoic Acids; D011458:Prostaglandins E; D011460:Prostaglandins F; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000244:Adenosine Diphosphate; D015237:Dinoprost; D011464:Epoprostenol; D007548:Isosorbide Dinitrate; D015232:Dinoprostone