PROSTANOID PRODUCTION IN HYPOXIC RAT ISOLATED ATRIA - INFLUENCE OF ACUTE DIABETES

The effects of hypoxia on prostanoid production were studied in atria from normal, acute diabetic and insulin-treated diabetic rats. Diabete s was induced by intravenous administration of 65 mg/kg of streptozoto cin, the rats were killed 5 days later. Hypoxia was performed by incub ation of the atria during 60 min in nitrogen-equilibrated glucose free Krebs'solution followed by 15 min of reoxygenation, The prostanoids 6 -keto prostaglandin F-1 alpha (6-keto PGF(1 alpha)) and thromboxane B- 2 (TXB(2)), stable metabolites of prostacyclin and TXA(2), respectivel y, as well as PGE(2), were measured by reversed phase HPLC-UV. In cont rol atria, the production of 6-keto PGF(1 alpha) was equivalent to tha t of PGE(2), whereas TXB(2) was released in a much smaller amount. In diabetic atria, 6-keto PGF(1 alpha) production was reduced by 65%, whe reas TXB(2) release was increased by 158% compared to the controls. Wh en the normal atria were exposed to 60 min ofhypoxia, the release of 6 -keto PGF(1 alpha) increased by 142% compared to basal values and rema ined elevated after 15 min of reoxygenation whereas in diabetic and in sulin-treated diabetic tissues the 6-keto PGF(1 alpha) production was not modified by the hypoxia-reoxygenation period. The release of TXB(2 ) 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 PGE(2) output increased only after the onset of the reoxygenation in the three groups studied. Since it is well known tha t prostacyclin exerts cytoprotective actions in cardiac tissues, the p resent results suggest that short-term diabetic atria could be more su sceptible to hypoxia-reoxygenation injuries.