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bioRxiv · 10.1101/2024.09.12.612758

Luminal Flow in the Connecting Tubule induces Afferent Arteriole Vasodilation

Wang, H.·Ortiz, P. A.·Romero, C. A.
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Abstract

BackgroundRenal 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. MethodsRabbit afferent arterioles (Af-Arts) with adjacent CNTs were microperfused ex-vivo with variable flow rates and sodium concentrations ranging from <1 mM to 80 mM and from 5 to 40 nL/min flow rates. ResultsPerfusion 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 ({beta}=0.163 {+/-} 0.04;p<0.001) and sodium concentration ({beta}=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. ConclusionIncreased 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.

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Wang, H., Ortiz, P. A., Romero, C. A.. 2024-09-17. Luminal Flow in the Connecting Tubule induces Afferent Arteriole Vasodilation. https://doi.org/10.1101/2024.09.12.612758

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