Determinants of relative amounts of medullary organic osmolytes: effects of NaCl and urea differ

Sorbitol, inositol, betaine, taurine, and glycerophosphorylcholine (GPC) are organic osmolytes that accumulate in the renal inner medulla during antidiuresis. In the cultured cell model, high medium sodium increases all the cell osmolytes and high medium urea increases cell GPC and inositol. It has been difficult, however, to discriminate between the effects of sodium and urea on organic osmolytes in water-deprived animals. To determine the nature of the in vivo responses of osmolyte accumulation induced by extracellular sodium or urea, we measured the medullary organic osmolytes and tested the degree of their linear correlation with urine and tissue parameters in control, dehydrated, salt-loaded, and urea-loaded rats. All of the osmolytes except myo-inositol increased in salt-loaded rats. Betaine and sorbitol contents in dehydrated rats were less than in salt-loaded rats, but other osmolytes increased significantly. Conversely, in urea-loaded rats, only GPC increased significantly, whereas either no change occurred for other osmolytes or sometimes betaine and sorbitol levels decreased. These data suggest that high sodium increases all of the osmolytes except myoinositol, whereas high urea increases only GPC and may decrease the renal medullary contents of betaine and sorbitol. We also demonstrated, using linear regression analysis, that urea and electrolyte in urine as well as tissue correlate well with each osmolyte measured.