Antioxidant Effect of Captopril and Enalapril on Reactive Oxygen Species-Induced Endothelial Dysfunction in the Rabbit Abdominal Aorta

Abstract

Background: Reactive oxygen species (ROS) are known to be related to cardiovascular diseases. Many studies have demonstrated that angiotensin-converting enzyme inhibitors have beneficial effects against ROS. We investigated the antioxidant effect of captopril and enalapril in nitric oxide mediated vascular endothelium-dependent relaxations. Materials and Methods: Isolated rabbit abdominal aorta ring segments were exposed to ROS by electrolysis of the organ bath medium (Krebs-Henseleit solution) after pretreatment with various concentrations (range, 10<SUP>-5</SUP> to 3×10<SUP>-4</SUP> M) of captopril and enalapril. Before and after electrolysis, the endothelial function was measured by preconstricting the vessels with norepinephrine (10<SUP>-6</SUP> M) followed by the cumulative addition of acetylcholine (range, 3×10<SUP>-8</SUP> to 10<SUP>-6</SUP> M). The relevance of the superoxide anion and hydrogen peroxide scavenging effect of captopril and enalapril was investigated using additional pretreatments of diethyldithiocarbamate (DETCA, 0.5 mM), an inhibitor of Cu/Zn superoxide dismutase, and 3-amino-1,2,4-triazole (3AT, 50 mM), an inhibitor of catalase. Results: Both captopril and enalapril preserved vascular endothelium-dependent relaxation after exposure to ROS in a dose-dependent manner (p＜0.0001). Pretreatment with DETCA attenuated the antioxidant effect of captopril and enalapril (p＜ 0.0001), but pretreatment with 3AT did not have an effect. Conclusion: Both captopril and enalapril protect endothelium against ROS in a dose-dependent fashion in isolated rabbit abdominal aortas. This protective effect is related to superoxide anion scavenging.