Effect of dipyridamole on prostanoid production in rat isolated atria

The effect of 0.01 mu M dipyridamole on prostanoid production was studied i n atria from normal, acute diabetic and insulin-treated diabetic rats. Diab etes 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) F-1 alpha (6-k eto-PGF(1 alpha)) and thromboxane (TX) B-2, stable metabolites of prostacyc lin and TXA(2), respectively, as well as PGE, were measured by reversed pha se high-performance liquid chromatography-UV. In diabetic atria, 6-keto-PGF (1 alpha) production was reduced by 50% whereas TXB2 release was increased two-fold compared to the controls, with a significant decrease in the 6-ket o-PGF(1 alpha)/TXB2 ratio. The preincubation with 0.01 mu M dipyridamole fo r 30 min increased 6-keto-PGF,, 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-PGF(1 alpha)/TXB2 ratio. In conclusion, STZ diabetes reduces the 6-keto-PGF(1 alpha)/TXB2 ratio impair ing the functional status of the atria. Dipyridamole increased this ratio i n atria from diabetic and insulin-treated diabetic rats, thus opposing the effects of STZ diabetes. This fact suggests the possibility of a participat ion of the drug in pathologies characterized by an imbalance in the product ion of vasodilator and vasoconstrictor prostanoids.