Inhibition of hyaluronan synthesis in rats reduces renal ability to excrete fluid and electrolytes during acute hydration.

Background: Hyaluronan (HA) is the dominant glycosaminoglycan in the renomedullary interstitium. Renomedullary HA has been implicated in tubular fluid handling due to its water-attracting properties and the changes occurring in parallel to acute variations in the body hydration status.

Methods: HA production was inhibited by 4-methylumbelliferone (4-MU in drinking water for 5 days, 1.45 ± 0.07 g/day/kg body weight) in rats prior to hydration.

Results: Following hypotonic hydration for 135 min in control animals, diuresis and osmotic excretion increased while sodium excretion and glomerular filtration rate (GFR) remained unchanged. The medullary and cortical HA contents were 7.85 ± 1.29 ng/mg protein and 0.08 ± 0.01 ng/mg protein, respectively. Medullary HA content after 4-MU was 38% of that in controls (2.98 ± 0.95 ng/g protein, p < 0.05), while the low cortical levels were unaffected. Baseline urine flow was not different from that in controls. The diuretic response to hydration was, however, only 51% of that in controls (157 ± 36 versus 306 ± 54 µl/g kidney weight/135 min, p < 0.05) and the osmolar excretion only 47% of that in controls (174 ± 47 versus 374 ± 41 µOsm/g kidney weight/135 min, p < 0.05). Sodium excretion, GFR, and arterial blood pressure were similar to that in control rats and unaltered during hydration.

Conclusions: Reduction of renomedullary interstitial HA using 4-MU reduces the ability of the kidney to respond appropriately upon acute hydration. The results strengthen the concept of renomedullary HA as a modulator of tubular fluid handling by changing the physicochemical properties of the interstitial space.