Effect of UUO on D1aR expression reveals a link among dopamine, transforming growth factor-beta, and nitric oxide.

Abstract

Interactions between transforming growth factor-beta (TGF-beta) and nitric oxide (NO) are important in the pathophysiology of unilateral ureteral obstruction (UUO). Dopamine (DA) is a vasoactive renal mediator active at the D(1A) receptor (D(1A)R), which has not been studied in UUO; therefore, we examined the interactions among DA, TGF-beta, and NO in UUO. In vivo, UUO was carried out in rats with or without concurrent treatment with 1D11, a monoclonal antibody to TGF-beta, for 14 days. In vitro, NRK-52E cells (normal rat kidney tubules) were treated with DA, and NO and TGF-beta release were examined. UUO resulted in a 70% decrease in the expression of renal D(1A)R, confirmed by both Western blot analysis and immunohistochemistry. 1D11 treatment restored expression to 60% of control values. DA treatment decreased NRK-52E release of TGF-beta by 80%; conversely, DA significantly increased NO release from NRK-52E cells. These results suggest that DA modulates the release of cytokines, which are involved in the fibrotic and apoptotic sequelae of UUO, and that these effects are independent of DA's known vasoactive properties.