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Am J Physiol Renal Physiol 290: F844-F853, 2006. First published September 27, 2005; doi:10.1152/ajprenal.00112.2005
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Exogenous 5'-nucleotidase improves glomerular autoregulation in Thy-1 nephritic rats

Tsuneo Takenaka,1 Hirokazu Okada,1 Yoshihiko Kanno,1 Tsutomu Inoue,1 Munekazu Ryuzaki,1 Hidetomo Nakamoto,1 Hiroshi Kawachi,2 Fujio Shimizu,2 and Hiromichi Suzuki1

1Department of Nephrology, Saitama Medical College, Iruma Saitama, and 2Department of Cell Biology, Institute of Nephrology, Niigata University, Niigata, Japan

Submitted 23 March 2005 ; accepted in final form 19 September 2005

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.

adenosine; ATP; sodium excretion; water excretion



Address for reprint requests and other correspondence: H. Suzuki, Dept. of Nephrology, Saitama Medical College, 38 Moro-hongo Moroyama, Iruma Saitama 350-0495, Japan (e-mail: iromichi{at}saitama-med.ac.jp)




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