Altered expression of prostacyclin synthase in a subset of the thick ascending limb cells and mesangial cells in 5/6-nephrectomized rats

The aim of this study was to evaluate the possible role of prostacyclin (PG I(2)) in the onset and development of hypertension and chronic renal failur e in 5/6-nephrectomized rats (5/6NX). We measured the systolic blood pressu re, 24-h urinary excretion levels of 6-keto-PGF(1 alpha), which was a stabl e metabolite of PGI(2), and levels of PGI(2) synthase (PCS) mRNA in the kid neys. Immunostaining for PCS in the kidneys was also evaluated. Systolic bl ood pressure was higher in 5/6NX than in sham-operated rats. The 24-h urina ry excretion levels of 6-keto-PGF(1 alpha) in 5/6NX at 1 week postsurgery w ere lower than in sham-operated rats. In renal morphology, tubulointerstiti al injury was observed at 2 weeks postsurgery, and glomerulosclerosis at 4 weeks. Levels of PCS mRNA in 5/6NX decreased significantly at 1 and 2 weeks postsurgery compared with those in sham-operated rats, but at 8 weeks thes e levels showed a tendency to increase. Immunostaining for PCS was positive in a subset of the cortical thick ascending limb of Henle's loop cells, in cluding macula densa in both groups. Moreover, in 5/6NX at 8 weeks postsurg ery, mesangial cells also stained positive for PCS. In conclusion, our find ings suggest that PCS might play an important role in mitigating glomerular hemodynamic changes associated with reduction of renal mass.