Effects of Magnesium Dobesilate on Nitric Oxide Synthase Activity in Endothelial Cells

This study was done to determine the effects of the angioprotective agent dobesilate on expression and activity on the constitutive nitric oxide synthase (ecNOS) in resident endothelial cells, as well as of the inducible nitric oxide synthase (iNOS) in cytokine-activated endothelial cells, by recording, in culture supernatants, the concentrations of citrulline as a reaction product of both enzymes. In capillary, microvascular, and macrovascular endothelial cells, Mg dobesilate incubation (0.25-1 mM) for 24 hours led to a highly significant concentration-correlating increase in ecNOS activities. These increases were not due to iNOS expression, and with cytokine-activated endothelial cell cultures that do express iNOS only moderate effects with little or no concentration dependency were seen. Addition of the NOS inhibitor NG-monomethyl-L-arginine (NMA) significantly suppresses citrulline formation in all cultures as evidence for the enzyme specificity.