Dept. of Molecular and Clinical Medicine/Nephrology, Institute of Medicine, The Sahlgrenska Academy at Univ. of Gothenburg, Vita Stråket 12, Sahlgrenska Univ. Hospital, S-413 45 Gothenburg, Sweden.
Am J Physiol Regul Integr Comp Physiol. 2010 Nov;299(5):R1142-9. doi: 10.1152/ajpregu.00326.2010. Epub 2010 Aug 18.
The aim of this study was to investigate dynamic autoregulation of renal blood flow (RBF) in ANG II-infused rats and the influence of high-NaCl intake. Sprague-Dawley rats received ANG II (250 ng·kg(-1)·min(-1) sc) or saline vehicle (sham) for 14 days after which acute renal clearance experiments were performed during thiobutabarbital anesthesia. Rats (n = 8-10 per group) were either on a normal (NNa; 0.4% NaCl)- or high (HNa; 8% NaCl)-NaCl diet. Separate groups were treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol; 1 M in drinking water). Transfer function analysis from arterial pressure to RBF in the frequency domain was used to examine the myogenic response (MR; 0.06-0.09 Hz) and the tubuloglomerular feedback mechanism (TGF; 0.03-0.06 Hz). MAP was elevated in ANG II-infused rats compared with sham groups (P < 0.05). RBF in ANG II HNa was reduced vs. sham NNa and sham HNa (6.0 ± 0.3 vs. 7.9 ± 0.3 and 9.1 ± 0.3 ml·min(-1)·g kidney wt(-1), P < 0.05). transfer function gain in ANG II HNa was significantly elevated in the frequency range of the MR (1.26 ± 0.50 dB, P < 0.05 vs. all other groups) and in the frequency range of the TGF (-0.02 ± 0.50 dB, P < 0.05 vs. sham NNa and sham HNa). Gain values in the frequency range of the MR and TGF were significantly reduced by tempol in ANG II-infused rats on HNa diet. In summary, the MR and TGF components of RBF autoregulation were impaired in ANG II HNa, and these abnormalities were attenuated by tempol, suggesting a pathogenetic role for superoxide in the impaired RBF autoregulatory response.
本研究旨在探讨血管紧张素 II（ANG II）输注大鼠肾血流（RBF）的动态自动调节及其对高盐摄入的影响。Sprague-Dawley 大鼠接受 ANG II（250ng·kg（-1）·min（-1）sc）或生理盐水载体（假手术）14 天后，在硫喷妥钠麻醉下进行急性肾清除实验。大鼠（每组 8-10 只）分别给予正常（NNa；0.4%NaCl）或高盐（HNa；8%NaCl）饮食。分别用 4-羟基-2,2,6,6-四甲基哌啶-1-氧自由基（tempol；1M 溶于饮用水）处理各组。应用动脉压至 RBF 的频域传递函数分析，研究肌源性反应（MR；0.06-0.09Hz）和管球反馈机制（TGF；0.03-0.06Hz）。与假手术组相比，ANG II 输注大鼠的平均动脉压升高（P<0.05）。与假手术 NNa 和假手术 HNa 相比，ANG II HNa 组的 RBF 降低（6.0±0.3 比 7.9±0.3 和 9.1±0.3ml·min（-1）·g 肾重（-1），P<0.05）。ANG II HNa 组的 MR 频率范围内的传递函数增益显著升高（1.26±0.50dB，P<0.05 与所有其他组）和 TGF 频率范围内的传递函数增益显著降低（-0.02±0.50dB，P<0.05 与假手术 NNa 和假手术 HNa）。在 HNa 饮食的 ANG II 输注大鼠中，tempol 显著降低了 MR 和 TGF 频率范围内的增益值。总之，ANG II HNa 中 RBF 自动调节的 MR 和 TGF 成分受损，这些异常通过 tempol 减弱，提示超氧化物在受损的 RBF 自动调节反应中具有发病作用。
