Luminal flow in the connecting tubule induces afferent arteriole vasodilation.

Abstract

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.