Effect of Exogenous and Endogenous Nitric Oxide on Endothelial Permeability Induced by Oxidants In Vitro

Abstract

Nitric oxide (NO) can be divided into two types: exogenous and endogenous. In this study we examined the effects of exogenous and endogenous NO on endothelial permeability induced by oxidants, such as hydrogen peroxide and super-oxide, using bovine pulmonary artery endothelial cells and a Chromatographic cell column technique. An NO donor, supermine-NONOate (SNO), at a concentration of 1 mM significantly exacerbated endothelial permeability induced by 0.1 mM peroxide by activating the Fenton reaction and reducing the intracellular glutathione level. Conversely, an NO synthase (NOS) inhibitor, L-N ⁵-(1-iminoethyl)-ornithine (L-NIO, 10 μM) completely inhibited peroxide-mediated permeability, suggesting that both exogenous and endogenous NO have aggressive effects on this event. On the other hand, SNO completely inhibited superoxide-mediated endothelial permeability by consuming the oxidant when flux of NO from an NO donor was similar to that of Superoxide from its generating system (xanthine plus xanthine oxidase). An NOS inhibitor, L-NIO (10 μM), did not affect this system. These results suggest that NO is a controversial chemical agent because it depends on the type of oxidant as to whether NO has defensive or aggressive effects on endothelial permeability induced by oxidants.