ANTIOXIDANT PYRROLIDINE DITHIOCARBAMATE PREVENTS DEFECTIVE BRADYKININ-STIMULATED CALCIUM ACCUMULATION AND NITRIC-OXIDE ACTIVITY FOLLOWING EXPOSURE OF ENDOTHELIAL-CELLS TO ELEVATED GLUCOSE-CONCENTRATION

Previous studies from our laboratory suggest that reactive oxygen cont ributes to diminished bradykinin-stimulated calcium accumulation in en dothelial cells exposed to elevated glucose concentrations. In this st udy, we evaluated the efficacy of the antioxidant pyrrolidine dithioca rbamate (PDTC), in preventing defects in intracellular calcium signall ing and nitric oxide (NO) activity in endothelial cells exposed to ele vated glucose concentration. We show that PDTC prevented the elevated glucose-induced impairment in bradykinin-stimulated calcium accumulati on without changing the normal calcium accumulation in response to ion omycin. Furthermore, the impaired cyclic GMP in RFL-6 detector cells ( an index of NO activity) generated by bradykinin-stimulation of high g lucose-exposed endothelial cells was restored to normal by pretreatmen t with PDTC. These studies support a role of reactive oxygen in elevat ed glucose-induced defects in calcium signalling and NO activity by en dothelial cells and that antioxidants may be useful in preventing this defect.