The cGMP Modulator, LY83583 Alters Oxygen Metabolites Differently in Cultured Endothelial Cells and Isolated Neutrophilic Granulocytes (original) (raw)

The present study was designed to assess the effect of LY83583 on H,OZ/O,-production from endothelial cells and neturophils, as determined by chemiluminiscence generation in vitro. We found that LY83583 increased H,02/0,production from endothelial cells, but inhibited the H20,/0,-production from phorbol myristate acetate-stimulated neutrophils. Furthermore, LY83583 consumed NADPH under certain conditions. Since neutrophils generate superoxide anion radicals via an NADPH-oxidase, we suggest that the reduction of chemiluminiscence, seen after addition of LY83583 to phorbol myristate acetate-stimulated neutrophils, is due to increased consumption of NADPH. In endothelial cells, NADPH is required as a co-factor in the generation of nitric oxide, which may interact with superoxide anion. A consumption in NAPDH would therefore be expected to decrease the production of nitric oxide and increase H,O,/ 0,-generation. The consumption of NADPH in endothelial cells could also cause reduced scavenger functions of the glutathion system, resulting in a further increase in H,02 release.