Hyaluronan (HA) displays unique water-binding capacity and is involved in renomedullary water handling. To elucidate mechanisms in the regulation of baseline levels of interstitial renomedullary HA in vivo and the elevation occurring in HA-levels during acute water loading, the involvement of hormones regulating fluid-electrolyte balance were investigated in anaesthetized rats.

The normal heterogenous intrarenal content of HA (high medullary and low cortical content) was confirmed and unaffected by 2h treatment with L-NAME (NOS-inhibitor) or indomethacin (COX-inhibitor) while vasopressin (AVP) tended to reduce medullary HA. During 2h acute water loading, the diuresis was accompanied by an elevation in renomedullary HA (+45%) while cortical HA was unaffected. In both the L-NAME and indomethacin-treated animals, the water loading-induced elevation in renomedullary HA was absent indicating a crucial involvement of NO and prostaglandins. After seven days of methylprednisolone treatment medullary HA was reduced by 40% but the water loading-induced elevation in HA remained intact.

In conclusion, the present study demonstrates important regulatory influence of hormones involved in fluid balance on renomedullary HA handling. The basal level of renomedullary interstitial HA does not, on a short term basis, rely on NO or prostaglandins. However, the elevation of renomedullary HA that follows acute water loading requires NO and prostaglandin tonus. Glucocorticoids reduce baseline levels of HA but do not interfere with water-induced elevation in HA suggesting different mechanistic pathways over HA synthases and hyaluronidases.