Enhanced urinary excretion of eicosanoids in fawn-hooded rats

Compared to Wistar (WAG) rats, rats of the fawn-hooded (FH) strain have a high level of glomerular filtration rate (GFR) and urinary protein excretion (UpV). To investigate the possible role of vasoactive eicosanoids in this spontaneous model of hyperfiltration and proteinuria, we compared the urinary excretion of thromboxane-B2 (TxB2), 6-keto-prostaglandin (Pg)F1 alpha and PgE2 in male FH and WAG rats during normal ageing. All measurements were performed sequentially in the same animals 12, 24, 36, 48 and 60 weeks after weaning. Throughout the study, GFR was higher in FH rats as were the filtration fraction and UpV. From week 24, UpV in FH rats increased progressively. No elevations in UpV were observed in WAG rats. At weeks 12 and 24, the urinary excretion of TxB2, 6-keto-PgF1 alpha and PgE2 was 2-4 times higher in FH rats compared to WAG rats. With time, a shift in the urinary excretion from vasodilator to vasoconstrictor eicosanoids was observed, i.e., the excretion of PgE2 declined and that of TxB2 increased. Proteinuria in FH rats was positively correlated with TxB2 excretion and negatively correlated with PgE2 excretion. We conclude that in FH rats, early hyperfiltration coincides with enhanced urinary excretion of all eicosanoids. Subsequent progressive proteinuria is associated with an increase in TxB2 and a decrease in PgE2 excretion.