Thorup C, Persson A E
Department of Physiology and Biophysics, Lund University, Sweden.
Am J Physiol. 1994 Oct;267(4 Pt 2):F606-11. doi: 10.1152/ajprenal.1994.267.4.F606.
This study was designed to compare the effects of systemic and intratubular infusions of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine (L-NNA) on the tubuloglomerular feedback (TGF) mechanism in anesthetized rats. We recently showed that intravenous infusion of L-NNA led to increases in mean arterial blood pressure (Pa), proximal tubular stop-flow pressure (Psf), and enhanced TGF sensitivity and reactivity. To avoid major systemic effects, in this study TGF was studied after intratubular NO inhibition. Intratubular infusion of L-NNA (10(-3) M) yielded similar results as shown with intravenous infusion, without systemic effects. TGF sensitivity and reactivity were increased, indicated by decreased turning point (TP) from 19.8 +/- 1.0 to 15.2 +/- 0.7 nl/min and increased delta Psf from 10.0 +/- 0.8 to 23.9 +/- 1.9 mmHg (24.3 vs. 59.1%). L-NNA at a concentration of 10(-4) M showed significant changes in both TP (from 20.9 +/- 1.1 to 17.8 +/- 1.0 nl/min) and delta Psf (from 7.6 +/- 0.6 to 13.9 +/- 0.7 mmHg), whereas 10(-5) M only increased delta Psf (9.7 +/- 1.0 vs. 12.1 +/- 1.1 mmHg). However, at low tubular perfusion rates Psf was not influenced by L-NNA. The early proximal flow rate (EPFR) showed no change at low tubular perfusion rates with L-NNA. At maximal TGF activation (40 nl/min), delta EPFR was increased from 34% in control to 62%. Our results suggest that NO not only regulates glomerular capillary pressure but also decreases the sensitivity of the TGF mechanism.
本研究旨在比较全身和肾小管内输注一氧化氮（NO）合酶抑制剂Nω-硝基-L-精氨酸（L-NNA）对麻醉大鼠肾小管球反馈（TGF）机制的影响。我们最近发现静脉输注L-NNA会导致平均动脉血压（Pa）、近端肾小管停流压力（Psf）升高，并增强TGF敏感性和反应性。为避免主要的全身效应，在本研究中，在肾小管内抑制NO后研究TGF。肾小管内输注L-NNA（10⁻³ M）产生了与静脉输注相似的结果，且无全身效应。TGF敏感性和反应性增加，转折点（TP）从19.8±1.0降至15.2±0.7 nl/min，Psf变化量（ΔPsf）从10.0±0.8升至23.9±1.9 mmHg（24.3%对59.1%）表明了这一点。浓度为10⁻⁴ M的L-NNA在TP（从20.9±1.1降至17.8±1.0 nl/min）和ΔPsf（从7.6±0.6升至13.9±0.7 mmHg）方面均有显著变化，而10⁻⁵ M仅增加了ΔPsf（9.7±1.0对12.1±1.1 mmHg）。然而，在低肾小管灌注率时，Psf不受L-NNA影响。在低肾小管灌注率且使用L-NNA时，早期近端流速（EPFR）无变化。在最大TGF激活（40 nl/min）时，ΔEPFR从对照时的34%增加到62%。我们的结果表明，NO不仅调节肾小球毛细血管压力，还降低TGF机制的敏感性。
