Aims: Recent studies have reported that intracellular calcium (Ca2+) mobilization is involved in homocysteine (Hcy)-induced endothelial dysfunction and the Na+/H+ exchanger (NHE) is responsible for an increase in the intracellular Ca2+ 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-a 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.

Keywords:
Homocysteine, Cariporide, Endothelial dysfunction, Oxidative stress, Nuclear factor-κB
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© 2013 S. Karger AG, Basel
2013
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