Increased Hyaluronic Acid in the Inner Renal Medulla of Obese Dogs

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Abstract
Abstract Dogs placed on a high-fat diet develop obesity and hypertension associated with marked sodium retention that is due to increased tubular reabsorption. Previous studies showed that renal interstitial hydrostatic pressure is elevated in obese dogs compared with lean dogs, and histological 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 glycosaminoglycans. The goal of this study was to quantitate medullary glycosaminoglycan content in obese (n=8) compared with lean (n=8) dogs. Measurement of total glycosaminoglycan content, estimated from uronic acid content, and of hyaluronate, the most abundant glycosaminoglycan in canine renal medulla, with an enzyme-linked immunosorbent assay indicated that there were no significant differences in total glycosaminoglycan or hyaluronate contents in the outer medulla of obese dogs compared with those 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 tissue, 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 suggest a change in the relative proportion of the glycosaminoglycan species in the inner medulla of obese dogs, with a selective increase in hyaluronate. These changes in extracellular matrix could contribute to the altered intrarenal physical forces, tubular compression, and increased tubular reabsorption observed in obese dogs.