Protective effects of cariporide on endothelial dysfunction induced by homocysteine.

Aims: Recent studies have reported that intracellular calcium (Ca(2+)) mobilization is involved in homocysteine (Hcy)-induced endothelial dysfunction and the Na(+)/H(+) exchanger (NHE) is responsible for an increase in the intracellular Ca(2+) concentration in cardiovascular disease. We hypothesized that inhibition of the NHE had protective effects on Hcy-induced endothelial dysfunction.

Methods: Acetylcholine-induced endothelium-dependent relaxation (EDR) and biochemical parameters were measured in the rat isolated aorta. The level of reactive oxygen species (ROS) was designed by a specific fluorescent probe. The phosphorylation of the nuclear factor-κB (NF-κB) system was studied by Western blot.

Results: Cariporide significantly prevented Hcy-impaired EDR and increased nitric oxide (NO) release; endothelial NO synthase activity simultaneously decreased ROS production. We also found that cariporide blocked Hcy-induced NF-κB activation and inhibitor-κB degradation, thus inhibiting the production of tumor necrosis factor-α and intercellular adhesion molecule-1.

Conclusions: The mechanisms of protective effects of cariporide may be related to the inhibition of NHE and the decrease in oxidative stress and inflammatory injury.