Protective effects of cariporide on endothelial dysfunction induced by homocysteine.

Abstract:

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.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Wu S,Gao X,Yang S,Liu L,Ge B,Yang Q

doi

10.1159/000356318

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

303-9

issue

5-6

eissn

0031-7012

issn

1423-0313

pii

000356318

journal_volume

92

pub_type

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