P89 Inhibition of endogenous hydrogen sulfide production decreases hypoxia induced erythropoietin release

Anemia of end stage renal disease (ESRD) affects 90% of hemodialysis patients and is a tremendous concern both for patients and health care providers. ESRD creates a state of renal hypoxia which may contribute to the lack of erythropoietin (EPO) production from the kidney when low O 2 levels are sensed, thus necessitating the use of exogenous EPO preparations. Recent discoveries indicate that endogenously derived hydrogen sulfide (H 2 S) may mediate oxygen sensing. Given the known involvement of other small molecules such as nitric oxide (NO) in EPO production and the observation of diminished urinary H 2 S levels in ESRD patients, we postulated that H 2 S may be the primary mediator of EPO production during hypoxia. Hep3B cells were incubated under hypoxic conditions (1% O 2 ) for 24 h at 37 °C. Hypoxic cells were treated with varying concentrations of H 2 S donor, GYY 4137, and inhibitors of H 2 S production, DL-propargylglycine (PAG) and hydroxylamine (HA). Following hypoxia EPO expression was measured by RT-PCR. In comparison to normoxia, hypoxic cells showed increased EPO expression. Administration of H 2 S production inhibitors HA and PAG led to significant decreases in EPO expression in hypoxic cells ( p p 2 S during hypoxia and subsequent EPO production. The use of novel oral H 2 S donors could represent a more efficacious and cost-effective alternative to standard therapies in treatment of anemia of ESRD.