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A Novel Mechanism of Renal Microcirculation Regulation: Connecting Tubule-Glomerular Feedback

  • Cesar A. RomeroEmail author
  • Oscar A. Carretero
Mechanisms of Hypertension and Target-Organ Damage (Matthew Weir, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Mechanisms of Hypertension and Target-Organ Damage

Abstract

Purpose of Review

In this review, we summarized the current knowledge of connecting tubule-glomerular feedback (CTGF), a novel mechanism of renal microcirculation regulation that integrates sodium handling in the connecting tubule (CNT) with kidney hemodynamics.

Recent Findings

Connecting tubule-glomerular feedback is a crosstalk communication between the CNT and the afferent arteriole (Af-Art), initiated by sodium chloride through the epithelial sodium channel (ENaC). High sodium in the CNT induces Af-Art vasodilation, increasing glomerular pressure and the glomerular filtration rate and favoring sodium excretion. CTGF antagonized and reset tubuloglomerular feedback and thus increased sodium excretion. CTGF is absent in spontaneous hypertensive rats and is overactivated in Dahl salt-sensitive rats. CTGF is also modulated by angiotensin II and aldosterone.

Summary

CTGF is a feedback mechanism that integrates sodium handling in the CNT with glomerular hemodynamics. Lack of CTGF could promote hypertension, and CTGF overactivation may favor glomerular damage and proteinuria. More studies are needed to explore the alterations in renal microcirculation and the role of these alterations in the genesis of hypertension and glomerular damage in animals and humans.

Key Points

CTGF is a vasodilator mechanism that regulates afferent arteriole resistance.

CTGF is absent in spontaneous hypertensive rats and overactivated in Dahl salt-sensitive rats.

CTGF in excess may promote glomerular damage and proteinuria, while the absence may participate in sodium retention and hypertension.

Keywords

Connecting tubule-glomerular feedback Tubuloglomerular feedback ENaC Hypertension Proteinuria 

Notes

Acknowledgments

We would like to thank Dr. Tengis Pavlov for the assistance in the figure preparation.

Funding

This study was funded by the Heart, Lung, and Blood Institute of the National Institutes of Health under award number HL-028982. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

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Authors and Affiliations

  1. 1.Hypertension and Vascular Research Division, Department of Internal MedicineHenry Ford HospitalDetroitUSA

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