Salt intake, endothelial cell signaling, and progression of kidney disease.
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-beta1 (TGF-beta1) and the endothelial isoform of nitric oxide synthase (NOS3). A balance is struck between TGF-beta1 and NOS3 as salt intake varies and creates a negative feedback loop, because TGF-beta1 increased expression of NOS3 and NO inhibited production of TGF-beta1 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.
Sanders
Paul W
PW
Nephrology Research and Training Center, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA. psanders@uab.edu
D000818:Animals; D002908:Chronic Disease; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D015398:Signal Transduction; D017673:Sodium Chloride, Dietary / Q000494:pharmacology* / Q000633:toxicity; D016212:Transforming Growth Factor beta / Q000502:physiology
D017673:Sodium Chloride, Dietary; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide