Menadione-induced vascular endothelial dysfunction and its possible significance

Although several studies have shown that treatment with menadione leads to endothelial cell cytotoxicity, investigations of menadione's effects on blood vessels are limited. Our previous studies have shown that menadione can indirectly induce alterations in vasomotor tone through platelet cytotoxicity. To determine if menadione affects vascular function, we investigated the effect of menadione on blood vessels using the isolated rat aortic rings in vitro organ bath system. Treatment with menadione directly resulted in contraction of aortic rings with endothelium but did not cause any effect on aortic rings without endothelium. Menadione irreversibly inhibited the acetylcholine- and histamine-induced relaxation of aortic rings with endothelium in a time- and concentration-dependent manner. Menadione treatment potentiated phenylephrine- and serotonin-induced vasoconstriction in aortic rings with endothelium. These in vitro results were observed at concentrations of menadione that are highly relevant to human therapeutics with menadione. When menadione was administrated intravenously to rats, blood pressure increased significantly in a concentration-dependent manner. Furthermore, menadione infusion suppressed the blood pressure reduction induced by acetylcholine. By demonstrating that menadione caused in vitro endothelial dysfunction (i.e., decreased relaxation and increased vasoconstriction in the organ bath experiments) and confirming that these results were consistent with in vivo observations, we have provided evidence suggesting that a quinone such as menadione can alter vasomotor tone through endothelial dysfunction. Such dysfunction could possibly contribute to vascular diseases.