Prostanoid production in hypoxic rat isolated atria: Influence of acute diabetes

Abstract

The effects of hypoxia on prostanoid production were studied in atria from normal, acute diabetic and insulin-treated diabetic rats. Diabetes was induced by intravenous administration of 65 mg/kg of streptozotocin, the rats were killed 5 days later. Hypoxia was performed by incubation of the atria during 60 min in nitrogen-equilibrated glucose free Krebs'solution followed by 15 min of reoxygenation. The prostanoids 6-keto prostaglandin F1α (6-keto PGF1α) and thromboxane B2 (TXB2), stable metabolites of prostacyclin and TXA2, respectively, as well as PGE2, were measured by reversed phase HPLC-UV. In control atria, the production of 6-keto PGF1α was equivalent to that of PGE2, whereas TXB2 was released in a much smaller amount. In diabetic atria, 6-keto PGF1α production was reduced by 65%, whereas TXB2 release was increased by 158% compared to the controls. When the normal atria were exposed to 60 min of hypoxia, the release of 6-keto PGF1α increased by 142% compared to basal values and remained elevated after 15 min of reoxygenation whereas in diabetic and insulin-treated diabetic tissues the 6-keto PGF1α production was not modified by the hypoxia-reoxygenation period. The release of TXB2 was increased after 60 min hypoxia in normal as well as in diabetic and insulin-treated diabetic tissues and remained elevated during the reoxygenation. The PGE2 output increased only after the onset of the reoxygenation in the three groups studied. Since it is well known that prostacyclin exerts cytoprotective actions in cardiac tissues, the present results suggest that short-term diabetic atria could be more susceptible to hypoxia-reoxygenation injuries.