Abstract
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.