Exogenous 5′-nucleotidase improves glomerular autoregulation in Thy-1 nephritic rats

Experiments were performed to characterize renal hemodynamics in Thy-1 nephritic rats. A monoclonal antibody against Thy-1 was intravenously injected to induce mesangiolysis in rats, and 2 days later renal hemodynamic responses to variations in blood pressure were determined. In the first series of experiments, autoregulation of renal plasma flow ( RPF) or glomerular filtration rate ( GFR) was impaired in nephritic rats. In response to a reduction in blood pressure ( 98 +/- 2 to 80 +/- 1 mmHg), both RPF ( 4.17 +/- 0.63 to 3.20 +/- 0.45 ml.min(-1).g kidney wt(-1), P < 0.05, n = 6) and GFR ( 0.88 +/- 0.05 to 0.75 +/- 0.06 ml.min(-1).g kidney wt(-1), P < 0.05) were decreased in nephritic rats. Intravenous administration of furosemide and 30% albumin, both of which inhibit tubuloglomerular feedback, diminished renal autoregulation in control but not nephritic rats. In the second studies, the infusion of 5'-nucleotidase, an enzyme expressed on mesangial cells, into a renal artery ameliorated the magnitude of autoregulatory decrements in GFR in nephritic rats ( -16 +/- 5 to -6 +/- 2%, P < 0.05, n = 6), but this enzyme failed to alter renal autoregulation in control rats. In the third studies, the effects of indomethacin were examined in nephritic rats. Inhibition of prostaglandin synthesis reduced RPF ( 4.07 +/- 0.30 to 1.54 +/- 0.22 ml.min(-1).g kidney wt(-1), P < 0.05, n = 5) and GFR ( 1.03 +/- 0.18 to 0.69 +/- 0.13 ml.min(-1).g kidney wt(-1), P < 0.05) in nephritic rats. However, cyclooxygenase inhibition failed to restore renal autoregulation in nephritic rats. Our results indicate that renal autoregulation is impaired in Thy-1 nephritis. Furthermore, the present data provide evidence that prostanoids contribute to maintain renal circulation in nephritic rats. Finally, our findings suggest that mesangial cells and/or 5'-nucleotidase plays an important role in mediating renal autoregulation.