Sodium storage in human tissues is mediated by glycosaminoglycan expression

Abstract

The current paradigm regarding sodium handling in animals and humans postulates that total body sodium is regulated predominately via regulation of extracellular volume. Active sodium storage independent of volume retention is thought to be negligible. However, studies in animals, hypertensive patients, and healthy humans suggest water-free storage of sodium in skin. We hypothesized that tissue sodium concentrations ([Na]T) found in humans vary and reflect regulation due to variable glycosaminoglycan content due to variable expression of XYLT-1. Twenty seven patients on dialysis and 21 living kidney transplant donors free of clinically detectable edema were studied. During surgery, abdominal skin, muscle, and arteries were biopsied. [Na]T was determined by inductively coupled plasma-optical emission spectrometry, semiquantitative glycosaminoglycan content with Alcian stain, and XYLT-1 expression by real-time PCR. [Na]T of arteries were ranging between 0.86 and 9.83 g/kg wet wt and were significantly higher in arteries (4.52 ± 1.82 g/kg) than in muscle (2.03 ± 1.41 g/kg; P < 0.001) or skin (3.24 ± 2.26 g/kg wet wt; P = 0.038). For individual patients [Na]T correlated for skin and arterial tissue ( r = 0.440, P = 0.012). [Na]T also correlated significantly with blinded semiquantitative analysis of glycosaminoglycans staining ( r = 0.588, P = 0.004). In arteries XYLT-1 expression was also correlated with [Na]T ( r = 0.392, P = 0.003). Our data confirm highly variable [Na]T in human skin and muscle and extend this observation to [Na]T in human arteries. These data support the hypothesis of water-independent sodium storage via regulated glycosaminoglycan synthesis in human tissues, including arteries.