Effect of dipyridamole on prostanoid production in rat isolated atria.
The effect of 0.01 microM dipyridamole on prostanoid production was studied in atria from normal, acute diabetic and insulin-treated diabetic rats. Diabetes was induced by i.v. administration of 65 mg/kg of streptozotocin (STZ) and the rats were killed 5 days later. Atria were incubated during 60 min in Krebs solution. The prostanoids 6-keto-prostaglandin (PG) F1alpha (6-keto-PGF1alpha) and thromboxane (TX) B2, stable metabolites of prostacyclin and TXA2, respectively, as well as PGE2 were measured by reversed phase high-performance liquid chromatography-UV. In diabetic atria, 6-keto-PGF1alpha production was reduced by 50% whereas TXB2 release was increased two-fold compared to the controls, with a significant decrease in the 6-keto-PGF1alpha/TXB2 ratio. The preincubation with 0.01 microM dipyridamole for 30 min increased 6-keto-PGF1alpha production in control, diabetic and insulin-treated diabetic atria whereas TXB2 release was not modified. This effects provoked an significant increase in the 6-keto-PGF1alpha/TXB2 ratio. In conclusion, STZ diabetes reduces the 6-keto-PGF1alpha/TXB2 ratio impairing the functional status of the atria. Dipyridamole increased this ratio in atria from diabetic and insulin-treated diabetic rats, thus opposing the effects of STZ diabetes. This fact suggests the possibility of a participation of the drug in pathologies characterized by an imbalance in the production of vasodilator and vasoconstrictor prostanoids.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D004176:Dipyridamole / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis; D014665:Vasodilator Agents / Q000494:pharmacology*