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. 2025 May;29(5):541-547.
doi: 10.1007/s10157-024-02615-2. Epub 2025 Jan 12.

Luminal flow in the connecting tubule induces afferent arteriole vasodilation

Hong Wang  1 , Pablo A Ortiz  1 , Cesar A Romero  2
Affiliations

Luminal flow in the connecting tubule induces afferent arteriole vasodilation

Hong Wang et al. Clin Exp Nephrol. 2025 May.

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.

Keywords: Afferent arterioles; Connecting tubule glomerular feedback (CNTGF); Distal sodium delivery; Epithelial sodium channel (ENaC); Renal blood flow; Superoxide (O2-).

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no financial conflict of interest to disclose. All experiments were conducted in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee (IACUC).

Update of

References

    1. Carlström M, Wilcox CS, Arendshorst WJ. Renal autoregulation in health and disease. Physiol Rev. 2015;95:405–511. - DOI - PubMed - PMC
    1. Romero CA, Carretero OA. Tubule-vascular feedback in renal autoregulation. Am J Physiol Renal Physiol. 2019;316:F1218–26. - DOI - PubMed - PMC
    1. Ren Y, Garvin JL, Liu R, Carretero OA. Crosstalk between the connecting tubule and the afferent arteriole regulates renal microcirculation. Kidney Int. 2007;71:1116–21. - DOI - PubMed
    1. Ren Y, D’Ambrosio MA, Garvin JL, Wang H, Carretero OA. Prostaglandin E2 mediates connecting tubule glomerular feedback. Hypertens Dallas Tex. 1979;2013(62):1123–8.
    1. Romero CA, Carretero OA. A novel mechanism of renal microcirculation regulation: connecting tubule-glomerular feedback. Curr Hypertens Rep. 2019;21:8. - DOI - PubMed - PMC

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