On the Mechanisms of the Neopterin-induced Suppression of Renal Erythropoietin Production

Abstract

Earlier neopterin was demonstrated to inhibit hypoxia-induced erythropoietin synthesis in isolated perfused rat kidneys. The present experiments were performed to gain further insight into the mode of action underlying this effect. Numerous studies provided evidence of a link between neopterin and oxidative stress as well as intraccllular calcium concentrations. Thus, neopterin (200 μM) NQS added into the perfusion medium together with either the caclium Channel blocker Verapamil (5 μM) or the anti-oxidant N-acetylcysteine (200 μM). The addition of neopterin as a Single stimulus resulted in a significant decrease in the rate of hypoxia-induced eryihropoietin release accompanied by an augmented renal vascular resistance and a reduced perfusion flow rate. Although these data point towards an involvement of calcium and/or reactive oxygen species, verapamil or Nacetyleysteine were able to abrogate the suppression of erythropoietin generation which was induced by neopterin. Therefore, the mechanisms responsible for the impact of neopterin on the production of this growih lactor in the kidney remain to be elucidated.

Keywords

• neopterin
• erythropoetin
• oxidative stress
• calcium