Endothelin, Ang II, vasopressin and osmolality regulate hyaluronan turnover by renomedullary interstitial cells suggesting an involvement of this matrix component in fluid handling (860.9)

Abstract

The content of the matrix component hyaluronan (HA) change in the medullary interstitium in relation to hydration status in vivo: elevated during hydration, reduced during dehydration suggesting a role in fluid handling by affecting interstitial fluid flux. We examined the effect of osmolality and fluid regulating hormones on HA‐turnover by RMIC in culture. Reducing media osmolality to simulate hydration, increased supernatant HA 4‐fold. Cell HA synthase (HAS) 2 and Hyaluronidase (Hyal) 2 mRNA expressions were unaltered while Hyal 1 mRNA was reduced by 35%. Supernatant Hyal activity was reduced by 44%. An inhibitor of Hyal activity (Asc‐P) elevated HA to similar high levels as low osmolality. AngII reduced HA by 58% and combined treatment with vasopressin reduced HA even further (69%). HAS and Hyal mRNA were stable while Hyal activity increased by 38% by AngII and 67% by the combination. Low dose endothelin (ET, 10‐10M) increased HA 3‐fold which was inhibited by ET‐B receptor blocker BQ788. On the contrary, high dose ET (10‐6M) reduced HA by 47%. The ET‐A receptor antagonist BQ123 not only reversed the reducing effect of high dose ET on HA but elevated it to the same level as low dose ET suggesting importance of ET‐B receptors. The study demonstrates a regulatory influence of osmolality and fluid regulating hormones on HA turnover, supporting the concept of an involvement of medullary interstitial HA in renal fluid handling by affecting interstitial permeability.Grant Funding Source: Supported by the Swedish Research Council‐Medicine