Takenaka Tsuneo, Okada Hirokazu, Kanno Yoshihiko, Inoue Tsutomu, Ryuzaki Munekazu, Nakamoto Hidetomo, Kawachi Hiroshi, Shimizu Fujio, Suzuki Hiromichi
Department of Nephrology, Saitama Medical College, Iruma Saitama 350-0495, Japan.
Am J Physiol Renal Physiol. 2006 Apr;290(4):F844-53. doi: 10.1152/ajprenal.00112.2005. Epub 2005 Sep 27.
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 x min(-1) x g kidney wt(-1), P < 0.05, n = 6) and GFR (0.88 +/- 0.05 to 0.75 +/- 0.06 ml x 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 x min(-1) x g kidney wt(-1), P < 0.05, n = 5) and GFR (1.03 +/- 0.18 to 0.69 +/- 0.13 ml x min(-1) x 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.
进行实验以表征Thy-1肾炎大鼠的肾血流动力学。静脉注射抗Thy-1单克隆抗体以诱导大鼠系膜溶解，2天后测定肾脏对血压变化的血流动力学反应。在第一系列实验中，肾炎大鼠的肾血浆流量（RPF）或肾小球滤过率（GFR）的自身调节受损。血压降低时（从98±2 mmHg降至80±1 mmHg），肾炎大鼠的RPF（从4.17±0.63降至3.20±0.45 ml·min-1·g肾重-1，P<0.05，n = 6）和GFR（从0.88±0.05降至0.75±0.06 ml·min-1·g肾重-1，P<0.05）均降低。静脉注射速尿和30%白蛋白，二者均抑制肾小管-肾小球反馈，可减弱对照大鼠而非肾炎大鼠的肾自身调节。在第二项研究中，将系膜细胞表达的一种酶5'-核苷酸酶注入肾动脉，可改善肾炎大鼠GFR自身调节降低的幅度（从-16±5%降至-6±2%，P<0.05，n = 6），但该酶未能改变对照大鼠的肾自身调节。在第三项研究中，检测了消炎痛对肾炎大鼠的影响。抑制前列腺素合成可降低肾炎大鼠的RPF（从4.07±0.30降至1.54±0.2 ml·min-1·g肾重-1，P<0.05，n = 5）和GFR（从1.03±0.18降至0.69±0.13 ml·min-1·g肾重-1，P<0.05）。然而，抑制环氧化酶未能恢复肾炎大鼠的肾自身调节。我们的结果表明，Thy-1肾炎中肾自身调节受损。此外，目前的数据提供了证据表明前列腺素有助于维持肾炎大鼠的肾循环。最后，我们的发现提示系膜细胞和/或5'-核苷酸酶在介导肾自身调节中起重要作用。
