ELEVATION OF THE THROMBOXANE A(2) PROSTACYCLIN RATIO IN URINE OF DIABETIC MICE ANALYZED BY GAS-CHROMATOGRAPHY SELECTED-ION MONITORING

Levels of the stable urinary metabolites of thromboxane B-2 and prosta cyclin, 11-dehydro-thromboxane B-2 (11-dehydro-TXB2) and 2,3-dinor-6-k eto-prostaglandin F-1 alpha (2,3-dinor-6-keto-PGF(1 alpha) ) were meas ured in diabetic mice to elucidate the relation between the thromboxan e A(2)/prostacyclin (TX/PGI) balance and pathological states of diabet es mellitus. 11-dehydro-TXB2 and 2,3-dinor-6-keto-PGF(1 alpha) were co nverted to 1-methyl er-propylamide-9,12,15-tris-dimethylisopropylsilyl (DMIPS) ether derivative and 1-methyl ester-6-methoxime-9, 12, 15-tri s-DMIPS ether derivative respectively, and applied to a gas chromatogr aphy/selected ion monitoring (GC/SIM). The urinary levels of 11-dehydr o-TXB2 and 2,3-dinor-6-keto-PGF(1 alpha) in streptozotocin (STZ)-treat ed mice showed a tendency to be higher and lower than those of non-tre ated mice, respectively. As a result, the TX/PGI ratios of the STZ dia betic mice were higher than those of normal mice. Furthermore, the rat ios of db/db mutant mice, rodent models of genetic diabetes, were incr eased with the progress of diabetes and showed positive correlations w ith the levels of blood glucose, hemoglobin A,,, and triglyceride, and negative correlation with insulin levels. These observations indicate that the TX/PGI ratio reflects the pathological condition of diabetes and partly explain the hypercoagulation in this disease.