Braam B, Koomans H A
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
Kidney Int. 1995 Nov;48(5):1406-11. doi: 10.1038/ki.1995.429.
The present study was designed to investigate whether nitric oxide (NO) antagonizes angiotensin II (Ang II) in modulating the tubuloglomerular feedback (TGF) system. Maximum TGF responses were assessed by evaluating stop-flow pressure (SFP) responses to late proximal perfusion with artificial tubular fluid (40 nl/min). Peritubular capillary (PTC) infusion of 10(-3) M NG-L-arginine (NLA) at a rate of 20 nl/min, and infusion of 10(-7) and 10(-6) M Ang II at rates that did not decrease SFP under conditions of zero flow to the macula densa (resting SFP), augmented maximum SFP feedback responses to 12.0 +/- 1.7, 12.1 +/- 2.4 and 16.9 +/- 3.0 mm Hg, respectively (all P < 0.01 vs. control response). Combined PTC infusion of NLA and 10(-7) M Ang II at a rate of 20 nl/min resulted in decreases in resting SFP in 7 of the 12 nephrons studied. When the infusion rate was decreased to 15 +/- 3 nl/min, concomitant PTC infusion of NLA and 10(-7) M Ang II was associated with a tremendous increase in maximum TGF responses (23.8 +/- 3.9 mm Hg; P < 0.01 vs. responses during PTC NLA or Ang II) in the absence of a decrease in resting SFP. During AT1 receptor blockade using losartan, SFP feedback responses were attenuated to 1.6 +/- 0.6 mm Hg and PTC infusion of NLA only augmented TGF responses to 3.8 +/- 1.0 mm Hg. These results strongly suggest that local NO antagonizes Ang II with respect to the regulation of TGF responsiveness. Disruption of this balance by NO synthesis inhibition strongly potentiates TGF-independent and TGF-dependent actions of Ang II on the preglomerular vasculature.
本研究旨在探究一氧化氮（NO）在调节球管反馈（TGF）系统中是否拮抗血管紧张素II（Ang II）。通过评估用人工肾小管液（40 nl/分钟）进行近端晚期灌注时的停流压力（SFP）反应来评估最大TGF反应。以20 nl/分钟的速率向肾小管周围毛细血管（PTC）输注10⁻³ M NG-L-精氨酸（NLA），并以在致密斑零流量条件下（静息SFP）不降低SFP的速率输注10⁻⁷和10⁻⁶ M Ang II，分别使最大SFP反馈反应增强至12.0±1.7、12.1±2.4和16.9±3.0 mmHg（与对照反应相比，所有P<0.01）。以20 nl/分钟的速率联合向PTC输注NLA和10⁻⁷ M Ang II，在研究的12个肾单位中有7个导致静息SFP降低。当输注速率降至15±3 nl/分钟时，同时向PTC输注NLA和10⁻⁷ M Ang II与最大TGF反应大幅增加（23.8±3.9 mmHg；与PTC输注NLA或Ang II期间的反应相比，P<0.01）相关，而静息SFP未降低。在使用氯沙坦进行AT1受体阻断期间，SFP反馈反应减弱至1.6±0.6 mmHg，仅向PTC输注NLA仅使TGF反应增强至3.8±1.0 mmHg。这些结果强烈表明，局部NO在调节TGF反应性方面拮抗Ang II。通过抑制NO合成破坏这种平衡会强烈增强Ang II对肾小球前血管系统的非TGF依赖性和TGF依赖性作用。
