Captopril restores endothelium-dependent relaxation induced by advanced oxidation protein products in rat aorta.

To explore whether advanced oxidation protein products (AOPP) can cause endothelial dysfunction in vitro, and whether captopril exerts beneficial effect on impaired endothelium-dependent relaxation induced by exogenous advanced oxidation protein products and to investigate the potential mechanisms. Both the Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside-induced endothelium-independent relaxation of aortic rings were measured by recording isometric tension after the rings were exposed to AOPP-BSA in the absence or presence of captopril to assess the injury effect of AOPP-BSA and the protective effect of captopril on the aortic endothelium, respectively. Co-incubation of aortic rings with AOPP-BSA (3 mmol/L) for 90 minutes resulted in a significant inhibition of EDR to ACh, but had no effects on endothelium-independent relaxation to SNP. After incubation of the rings in the co-presence of captopril (3 to 30 micromol/L) or enalaprilat (30 micromol/L) with AOPP-BSA (3 mmol/L) for 90 minutes, captopril significantly and enalaprilat only partly attenuated the inhibition of EDR induced by AOPP-BSA. This protective effect of captopril (30 micromol/L) was abolished by N-nitro-L-arginine methyl ester (10 micromol/L), an inhibitor of nitric oxide synthase. Furthermore, the superoxide anion scavenger superoxide dismutase (SOD, 200 U/mL), and the nitric oxide precursor L-arginine (3 mmol/L) also ameliorated the impaired EDR caused by AOPP-BSA. But D-arginine had no effect on the impaired EDR caused by AOPP-BSA. AOPP-BSA can trigger endothelial dysfunction and captopril can protect the endothelium against functional damage induced by AOPP-BSA in rat aorta, increase nitric oxide bioavailability. The mechanisms of endothelial dysfunction induced by AOPP-BSA may include the decrease of NO and the generation of oxygen-free radicals.