Renal production of thromboxane and prostaglandins in a rat model of type 2 diabetes

In an investigation of the involvement of prostanoids in the pathogenesis o f nephropathy in type 2 diabetes, we repeatedly measured the urinary excret ion of prostanoids in both diabetic and healthy rats as the mts aged. Seven rats of the Otsuka Long-Evans Tokushima Fatty strain were used as rats wit h a model of type 2 diabetes and seven rats of the Long-Evans Tokushima Ots uka strain were used as rats without diabetes. Thromboxane (TX) B2 and 6-ke to-prostaglandin (PG) F1 alpha, the amounts of which reflect renal producti on of TXA2 and PGI2, respectively, and PGE2 in urine collected in metabolic cages were assayed when rats were 14, 30, 46, and 54 weeks old. Plasma glu cose and urinary protein excretion also were measured periodically. The mea n plasma glucose concentration of the diabetic rats was higher than that of the healthy rats throughout the study. At 30 weeks and later, urinary prot ein excretion by the diabetic rats was greater than that of the healthy rat s, and it increased with age. Urinary excretion of TXB2 by the diabetic rat s was higher than that of the healthy rats at 14 weeks (52.4 +/- 23.5 vs. 2 7.0 +/- 2.6 ng/day; mean +/- SD, P =.015) and the difference continued to t he end of the experiment. Urinary excretion of 6-keto-PGF1 alpha by the dia betic rats was high at 14 weeks (52.3 +/- 12.8 vs. 26.9 +/- 4.6 ng/day; mea n +/- SD, P <.001) but decreased with age and was the same as that of the h ealthy rats at 54 weeks. The urinary excretion of PGE2 by the two groups of rats was not significantly different. These results suggest that altered r enal production of TXA2 and PGI2 is involved in the pathogenesis of diabeti c nephropathy in rats with type 2 diabetes.