Published Online
on January 5, 2004

A more recent version of this article appeared on February 1, 2004

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Submitted on October 27, 2003
Revised on November 14, 2003

Salt Intake, Endothelial Cell Signaling, and Progression of Kidney Disease

Paul W. Sanders^*

From Nephrology Research and Training Center, Comprehensive Cancer Center, Cell Adhesion and Matrix Research Center, Division of Nephrology, Department of Medicine, and Department of Physiology & Biophysics, University of Alabama at Birmingham, and Department of Veterans Affairs Medical Center, Birmingham.

^* To whom correspondence should be addressed. E-mail: psanders{at}uab.edu.

Abstract--It has been known for decades that increased dietary intake of salt (NaCl) shortens the life span of rats in a dose-dependent fashion. This review focuses specifically on the recently described biological effect and consequences of increased salt ingestion on the endothelium through a mechanism that is independent of blood pressure. Changes in salt intake are recognized by endothelial cells in the vascular tree and glomeruli through a physical process that promotes a series of signaling events involved in transcriptional regulation of genes that include transforming growth factor-1 (TGF-1) and the endothelial isoform of nitric oxide synthase (NOS3). A balance is struck between TGF-1 and NOS3 as salt intake varies and creates a negative feedback loop, because TGF-1 increased expression of NOS3 and NO inhibited production of TGF-1 in healthy rats. Changes in this feedback system have been observed in salt-sensitive hypertension and appear to impact end-organ damage, particularly the kidney. The data support an important benefit to reduction of salt intake in the setting of chronic kidney disease.

Key words: endothelium • vascular disease • nitric oxide • gene expression • hypertension

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