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(Hypertension. 2004;43:142.)
© 2004 American Heart Association, Inc.

Brief Review

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

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.

Correspondence to Dr Paul W. Sanders, Division of Nephrology/Department of Medicine, 642 Lyons-Harrison Research Building, 1530 Third Avenue, South, University of Alabama at Birmingham, Birmingham, AL 35294-0007. E-mail psanders{at}uab.edu

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-ß1 (TGF-ß1) and the endothelial isoform of nitric oxide synthase (NOS3). A balance is struck between TGF-ß1 and NOS3 as salt intake varies and creates a negative feedback loop, because TGF-ß1 increased expression of NOS3 and NO inhibited production of TGF-ß1 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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