Aims: 

Hyaluronan (HA) is the dominant glycosaminoglycan in the renal medullary interstitium while the content in the cortex is very low. HA has been implicated in tubular fluid handling due to its water attracting properties and the dynamic regulation of the renomedullary interstitial HA levels which occur in parallel to acute variations in body hydration status. To directly test the importance of renal HA in fluid regulation the following study was performed.

Methods: 

HA production was inhibited by 4-methylumbelliferone (4-MU in drinking water for five days, 1.47 g/day/kg body weight) in rats prior to hypotonic hydration.

Results: 

Following hydration for 135 min in control animals, diuresis and osmotic excretion increased while sodium excretion and GFR remained unchanged. The renomedullary HA content was 7.85±1.29 ng/mg protein while that in the cortex was 0.08±0.01 ng/mg protein. In animals treated with 4-MU the renomedullary HA content was 38% of that in control animals (2.98±0.95 ng/g protein, p< 0.05) while the low levels in the cortex were not different from control rats (0.09±0.01 ng/mg protein). Baseline urine flow prior to hydration was not different from control animals. The diuretic response to hydration was, however, only 51% of that in the control animals and the osmolar excretion was only 47% of that in control animals. Sodium excretion and GFR were similar to control rats and remained unaltered during hydration.

Conclusion: 

Reduction of renomedullary interstitial HA using 4-MU reduces the ability of the kidney to respond with an appropriate excretory response upon acute hydration. The results strengthen the concept of renomedullary HA as a determinant of tubular fluid handling by changing the physicochemical properties of the interstitial space.