The past two decades of endothelium-related research have altered our concepts of the function of this organ significantly. Endothelial cells (ECs) are metabolically active input–output sensors that detect and respond to mechanical and biochemical changes in the extracellular environment. Recent work has further promoted the concept that the endothelium can react to changes in dietary NaCl (also referred to as salt in this chapter) intake independently of blood pressure through changes in the extracellular milieu, particularly shear force. EC function appears to be a critical factor involved in the vascular response to changes in salt intake.
DIETARY SALT ALTERS ENDOTHELIAL CELL PRODUCTION OF TRANSFORMING GROWTH FACTOR-β AND NITRIC OXIDE
Initial studies examined the effect of salt intake on production of transforming growth factor (TGF)-β in the kidney. Expression of all three mammalian TGF-β family members – TGF-β1, β2, and β3 – increased in renal cortical tissue from rats fed a diet containing 8.0% NaCl (high salt), compared to tissue from rats maintained on a 0.3% NaCl (low salt) diet (1). Subsequent experiments focused on production of TGF-β1. Steady state mRNA levels and production of total and active TGF-β1 were increased in glomerular preparations (1) and aortic rings (2) from rats on the high-salt diet, compared to preparations from rats on the low-salt diet. Increased TGF-β1 levels were no longer detected when aortic ring preparations were denuded of their endothelium, demonstrating that the endothelium was the source of the TGF-β1. Immunohistochemical analyses of aorta from rats on the high-salt, but not low-salt, diet revealed increased nuclear accumulation of phosphorylated Smad2/3 in the EC lining (Figure 140.1A), suggesting that TGF-β1 is signaling in ECs.