The effect of isosorbide dinitrate and isosorbide-5-mononitrate on prostacyclin (PGI2) and thromboxane A2 (TXA2) generation in rat and human arteries.
The mechanism by which nitrates produce relaxation of the vascular smooth muscle and anti-aggregatory effect on platelets has not been understood. Several reports have suggested that vasoactive prostaglandin generation may account for part of the pharmacological action of nitroglycerin. However, few studies have been reported that isosorbide dinitrate or its main metabolite, isosorbide-5-mononitrate, directly stimulates prostacyclin (PGI2) generation in blood vessels. We examined the effect of ISDN and 5-ISMN on PGI2 and thromboxane A2 (TXA2) generation in rat thoracic aorta and human thoracic aorta and coronary artery. The stimulation of PGI2 generation was dependent on the concentration of ISDN and the maximum PGI2 generation was effected by ISDN 5.0 ng/ml in both rat and human vessels. The ratio of peak to basal PGI2 generation was about 1.6 with rat thoracic aorta and about 1.6 with human thoracic aorta and about 1.3 with human coronary artery. On the other hand, TXA2 generation showed a smaller increase than that of PGI2 with ISDN used in the therapeutic dose range and 5-ISMN did not significantly affect PGI2 or TXA2 generation. Previous studies of the effect of cyclooxygenase inhibitor, for example indomethacin, on the vasodilating response to nitrates have given conflicting results. It is believed, however, that ISDN is partially, not wholly, associated with the hemodynamic and platelet antiaggregation effects due to vascular PGI2 generation, which may play a beneficial role in inhibiting coronary vasospasm during anginal attacks.
D000368:Aged; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000378:metabolism*; D013931:Thromboxanes / Q000378:metabolism*; D014665:Vasodilator Agents
D013931:Thromboxanes; D014665:Vasodilator Agents; D013928:Thromboxane A2; D011464:Epoprostenol; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate