Experiments were performed to characterize renal hemodynamics in Thy-1 nephritic rats. 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 reduction in blood pressure (98±2 to 80±1 mmHg), both RPF (4.17±0.63 to 3.20±0.45 ml/min/g.kidney.wt, p<0.05, n=6) and GFR (0.88±0.05 to 0.75±0.06 ml/min/g.kidney.wt, 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 renal artery ameliorated the magnitude of autoregulatory decrements of 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/g.kidney.wt, p<0.05, n=5) and GFR (1.03±0.18 to 0.69±0.13 ml/min/g.kidney.wt, p<0.05) in nephritic rats. However, cyclo-oxygenase 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 play an important role in mediating renal autoregulation.