EFFECT OF GLICLAZIDE ON PROSTAGLANDIN I2 FORMATION IN NORMAL AND STREPTOZOTOCIN-INDUCED DIABETIC ANIMALS

The effect of gliclazide, a hypoglycemic sulfonylurea, on the formation of prostaglandin (PG) I2 by the aortic rings of normal and streptozotocin-induced diabetic animals was studied. In in vitro experiments, gliclazide (100-300 μg/ml) enhanced the spontaneous PGI2 formation by the guinea-pig and rat aorta. Gliclazide also enhanced the transformation of both arachidonic acid and PGH2 to PGI2 in guinea-pig aorta, indicating that one of the main enhancing sites is the step of converting PGH2 to PGI2. In ex vivo experiments, the formation of PGI2 in the aorta of streptozotocin-diabetic rats was markedly reduced as compared with that of normal rats. An oral administration of gliclazide (100-300 mg/kg) significantly restored this reduced formation of PGI2 without any effect on blood glucose level. This enhancing effect of gliclazide may be favorable to the treatment of diabetic microangiopathy.