Hypertension and Vascular Research Div., Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, USA.
Am J Physiol Renal Physiol. 2012 May 15;302(10):F1300-4. doi: 10.1152/ajprenal.00673.2011. Epub 2012 Feb 22.
Tubuloglomerular feedback (TGF) and connecting tubule glomerular feedback (CTGF) are mechanisms that control afferent arteriole (Af-Art) tone. TGF, initiated by increased NaCl at the macula densa, causes Af-Art constriction. Prolonged activation of TGF leads to an attenuation or "resetting" of its constrictor effect. The mechanisms of TGF resetting remain incompletely understood. CTGF is initiated by increased NaCl in the connecting tubule and Na(+) entry via epithelial sodium channels (ENaC). Contrary to TGF, CTGF dilates the Af-Art. Here, we hypothesize that CTGF, in part, mediates TGF resetting. We performed micropuncture of individual rat nephrons while measuring stop-flow pressure (P(SF)), an index of glomerular filtration pressure and Af-Art tone. Increases in Af-Art tone cause P(SF) to decrease. TGF responses, measured as the decrease in P(SF) induced by switching late proximal tubule perfusion from 5 to 40 nl/min, were elicited before and after a 30-min period of sustained perfusion of the late proximal tubule at a rate of 40 nl/min designed to induce TGF resetting. TGF responses were 7.3 ± 0.3 and 4.9 ± 0.2 mmHg before and after resetting was induced (P < 0.001, n = 6). When CTGF was inhibited with the ENaC blocker benzamil (1 μM), TGF responses were 9.5 ± 0.3 and 8.8 ± 0.6 mmHg (NS, n = 6), thus resetting was abolished. In the presence of the carbonic anhydrase inhibitor acetazolamide (10 mM), TGF responses were 8.8 ± 0.6 and 3.3 ± 0.4 mmHg before and after resetting (P < 0.001, n = 6). With both acetazolamide and benzamil, TGF responses were 10.4 ± 0.2 and 8.4 ± 0.5 mmHg (P < 0.01, n = 6), thus resetting was attenuated. We conclude that CTGF, in part, mediates acutely induced TGF resetting.
管球反馈（TGF）和连接小管球反馈（CTGF）是控制入球小动脉（Af-Art）张力的机制。TGF 由致密斑处 NaCl 增加引发，导致 Af-Art 收缩。TGF 的长期激活导致其收缩作用的衰减或“重置”。TGF 重置的机制仍不完全清楚。CTGF 由连接小管中 NaCl 增加和上皮钠通道（ENaC）介导的 Na+内流引发。与 TGF 相反，CTGF 扩张 Af-Art。在这里，我们假设 CTGF 在一定程度上介导了 TGF 的重置。我们在测量停流压（P(SF)）的同时对单个大鼠肾单位进行微穿刺，P(SF)是肾小球滤过压和 Af-Art 张力的指标。Af-Art 张力增加会导致 P(SF)下降。TGF 反应是通过将晚期近端小管的灌流从 5 至 40 nl/min 切换来测量的，即降低 P(SF)，我们在晚期近端小管以 40 nl/min 的速率持续灌流 30 分钟以诱导 TGF 重置之前和之后引发 TGF 反应。TGF 反应在重置前分别为 7.3 ± 0.3 和 4.9 ± 0.2 mmHg（P < 0.001，n = 6），在诱导重置后分别为 9.5 ± 0.3 和 8.8 ± 0.6 mmHg（无统计学差异，n = 6）。当用上皮钠通道阻滞剂苯甲脒（1 μM）抑制 CTGF 时，TGF 反应分别为 9.5 ± 0.3 和 8.8 ± 0.6 mmHg（无统计学差异，n = 6），因此重置被消除。在碳酸酐酶抑制剂乙酰唑胺（10 mM）存在的情况下，TGF 反应在重置前分别为 8.8 ± 0.6 和 3.3 ± 0.4 mmHg（P < 0.001，n = 6），在重置后分别为 3.3 ± 0.4 和 1.5 ± 0.2 mmHg（P < 0.001，n = 6）。在同时使用乙酰唑胺和苯甲脒的情况下，TGF 反应分别为 10.4 ± 0.2 和 8.4 ± 0.5 mmHg（P < 0.01，n = 6），因此重置被减弱。我们得出结论，CTGF 在一定程度上介导了急性诱导的 TGF 重置。
