INCREASED HYALURONIC-ACID IN THE INNER RENAL MEDULLA OF OBESE DOGS

Dogs placed on a high-fat diet develop obesity and hypertension associ ated with marked sodium retention that is due to increased tubular rea bsorption. Previous studies showed that renal interstitial hydrostatic pressure is elevated in obese dogs compared with lean dogs, and histo logical studies revealed increases in medullary interstitial cells and expansion of the medullary but not the cortical extracellular matrix. This matrix stained intensively with Alcian Blue at pH 2.6, colloidal iron, and periodic acid-Schiff, suggesting increased glycosaminoglyca ns. The goal of this study was to quantitate medullary glycosaminoglyc an content in obese (n=8) compared with lean (n=8) dogs. Measurement o f total glycosaminoglycan content, estimated from uronic acid content, and of hyaluronate, the most abundant glycosaminoglycan in canine ren al medulla, with an enzyme-linked immunosorbent assay indicated that t here were no significant differences in total glycosaminoglycan or hya luronate contents in the outer medulla of obese dogs compared with tho se in lean dogs. In contrast, in the inner medulla of obese dogs there was a 140% increase in hyaluronate compared with the content in lean dogs (4.3 +/- 0.5 versus 1.8 +/- 0.2 mg hyaluronate per gram wet tissu e, respectively; P<.05); however, total glycosaminoglycan content was not significantly different (6.9 +/- 0.7 versus 6.2 +/- 0.5 mg uronic acid per gram wet tissue) in obese and lean dogs. These results sugges t a change in the relative proportion of the glycosaminoglycan species in the inner medulla of obese dogs, with a selective increase in hyal uronate. These changes in extracellular matrix could contribute to the altered intrarenal physical forces, tubular compression, and increase d tubular reabsorption observed in obese dogs.