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, 10⁻⁵ to 3*10⁻⁴ M) of captopril and enalapril. Before and after electrolysis, the endothelial function was measured by preconstricting the vessels with norepinephrine (10⁻⁶ M) followed by the cumulative addition of acetylcholine (range, 3*10⁻⁸ to 10⁻⁶ 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.