Effect of dipyridamole on prostanoid production in rat isolated atria

Abstract

The effect of 0.01 μM 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) F1α(6-keto-PGF1α) and thromboxane (TX) B2, stable metabolites of prostacyclin and TXA2, respectively, as well as PGE2were measured by reversed phase high-performance liquid chromatography-UV. In diabetic atria, 6-keto-PGF1αproduction was reduced by 50% whereas TXB2release was increased two-fold compared to the controls, with a significant decrease in the 6-keto-PGF1α/TXB2ratio. The preincubation with 0.01 μM dipyridamole for 30 min increased 6-keto-PGF1αproduction in control, diabetic and insulin-treated diabetic atria whereas TXB2release was not modified. This effects provoked an significant increase in the 6-keto-PGF1α/TXB2ratio. In conclusion, STZ diabetes reduces the 6-keto-PGF1α/TXB2ratio 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.