Inhibition Of Superoxide Anion-mediated Impairment Of Endothelium By Treatment With Luteolin And Apigenin In Rat Mesenteric Artery

Background and purpose: Endothelial production of reactive oxygen species, especially superoxide anion is an important mechanism of vascular dysfunction in cardiovascular diseases. This study was designed (i) to test the hypothesis that the endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide (NO) components of acetylcholine (Ach)-induced vasorelaxation and hyperpolarization of smooth muscle cell (SMC) are impaired following exposure to superoxide anion, and (ii) to further investigate the vasoprotection of total flavonoids of Flos Chrysanthemi (TFFC), and its main bioactive components, luteolin and apigenin at the vasoactive concentration, on impaired endothelial function.Experimental approaches: Rat mesenteric arterial rings were isolated for isometric force recording and electrophysiological studies. Perfusion pressure of mesenteric arterial bed was measured and visualization of superoxide production was detected with fluorescent dye dihydroethidium. Key results: 300 μM pyrogallol significantly decreased the relaxation andhyperpolarization to ACh. Oral administration with TFFC significantly improved the decrease in perfusion pressure in the mesenteric arterial bed. Luteolin and apigenin both induced vasoprotection against loss of the EDHF and NO components of ACh-induced relaxation and attenuated the impairment of hyperpolarization to ACh. Oxidative fluorescent microtopography showed that either luteolin or apigenin significantly reduced the superoxide levels.Conclusions and implications: The results suggest that exposure to superoxide anion impairs ACh-induced relaxation and hyperpolarization of SMC in resistance arteries through the impairment of both EDHF- and NO-mediated relaxation. Luteolin and apigenin protect resistance arteries from injury by superoxide anion, implying that they may be effective in the therapy of vascular diseases associated with oxidative stress.