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Background <p>Renal autoregulatory mechanisms modulate renal blood flow. Connecting tubule glomerular feedback (CNTGF) is a vasodilator mechanism in the connecting tubule (CNT), triggered paracrinally when high sodium levels are detected via the epithelial sodium channel (ENaC). The primary activation factor of CNTGF—whether NaCl concentration, independent luminal flow, or the combined total sodium delivery—is still unclear. We hypothesized that increasing luminal flow in the CNT induces CNTGF via O2<sup>−</sup> generation and ENaC activation.</p> Methods <p>Rabbit afferent arterioles (Af-Arts) with adjacent CNTs were microperfused <i>ex-vivo</i> with variable flow rates and sodium concentrations ranging from &lt; 1 to 80&#xa0;mM and from 5 to 40 nL/min flow rates.</p> Results <p>Perfusion of the CNT with 5&#xa0;mM NaCl and increasing flow rates from 5 to 10, 20, and 40 nL/min caused a flow-rate-dependent dilation of the Af-Art (<i>P</i> &lt; 0.001). Adding the ENaC blocker benzamil inhibited flow-induced Af-Art dilation, indicating a CNTGF response. In contrast, perfusion of the CNT with &lt; 1&#xa0;mM NaCl did not result in flow-induced CNTGF vasodilation (<i>P</i> &gt; 0.05). Multiple linear regression modeling (R<sup>2</sup> = 0.51; <i>P</i> &lt; 0.001) demonstrated that tubular flow (β = 0.163 ± 0.04; <i>P</i> &lt; 0.001) and sodium concentration (β = 0.14 ± 0.03; <i>P</i> &lt; 0.001) are independent variables that induce afferent arteriole vasodilation. Tempol reduced flow-induced CNTGF, and L-NAME did not influence this effect.</p> Conclusion <p>Increased luminal flow in the CNT induces CNTGF activation via ENaC, partially due to flow-stimulated O2- production and independent of nitric oxide synthase (NOS) activity.</p>

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Luminal flow in the connecting tubule induces afferent arteriole vasodilation

  • 期刊论文

  • 发表日期：

    2025年1月12日

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  • Hong Wang,
  • Pablo A. Ortiz,
  • Cesar A. Romero

摘要

Background

Renal autoregulatory mechanisms modulate renal blood flow. Connecting tubule glomerular feedback (CNTGF) is a vasodilator mechanism in the connecting tubule (CNT), triggered paracrinally when high sodium levels are detected via the epithelial sodium channel (ENaC). The primary activation factor of CNTGF—whether NaCl concentration, independent luminal flow, or the combined total sodium delivery—is still unclear. We hypothesized that increasing luminal flow in the CNT induces CNTGF via O2− generation and ENaC activation.

Methods

Rabbit afferent arterioles (Af-Arts) with adjacent CNTs were microperfused ex-vivo with variable flow rates and sodium concentrations ranging from < 1 to 80 mM and from 5 to 40 nL/min flow rates.

Results

Perfusion of the CNT with 5 mM NaCl and increasing flow rates from 5 to 10, 20, and 40 nL/min caused a flow-rate-dependent dilation of the Af-Art (P < 0.001). Adding the ENaC blocker benzamil inhibited flow-induced Af-Art dilation, indicating a CNTGF response. In contrast, perfusion of the CNT with < 1 mM NaCl did not result in flow-induced CNTGF vasodilation (P > 0.05). Multiple linear regression modeling (R2 = 0.51; P < 0.001) demonstrated that tubular flow (β = 0.163 ± 0.04; P < 0.001) and sodium concentration (β = 0.14 ± 0.03; P < 0.001) are independent variables that induce afferent arteriole vasodilation. Tempol reduced flow-induced CNTGF, and L-NAME did not influence this effect.

Conclusion

Increased luminal flow in the CNT induces CNTGF activation via ENaC, partially due to flow-stimulated O2- production and independent of nitric oxide synthase (NOS) activity.