Apigenin protects endothelium-dependent relaxation of rat aorta against oxidative stress

Apigenin is shown to have cardiovascular effects, but the effects of apigenin on aortas injured by exogenous oxidants are unknown. The objective of this study was to investigate the effect of apigenin on endothelium-dependent vasorelaxation in isolated rat aortic rings exposed to superoxide anion produced by pyrogallol, and its mechanism. The male Sprague-Dawley rat thoracic aorta was rapidly dissected out and the effect of apigenin on tension of aortic rings pretreated with 500 mu M pyrogallol, inducing oxidative stress injury, was measured. The activity of nitric oxide synthase (NOS), the level of nitric oxide (NO) and the inhibition of superoxide anion in aortic tissues were measured. We found that pretreatment with pyrogallol concentration-dependently decreased acetylcholine-induced endothelium-dependent vasorelaxation. Apigenin (0.5-72.0 mu M) evoked a concentration-dependent relaxation in aortas (pD(2): 5.304 +/- 0.049), which was weakened by L-NAME (the maximal relaxation fell from 87.6 +/- 6.7% to 37.1 +/- 8.8%, P<0.01), but not by aminoguanidine and indomethacin. Apigenin markedly attenuated the inhibition of vasorelaxation induced by pyrogallol (the maximal relaxation elevated from 55.8% +/- 6.6% to 69.5% +/- 6.4%, and the pD(2) increased from 6.559 +/- 0.119 to 7.057 +/- 0.145, P<0.01) and increased the inhibition of superoxide anion (from 94.6% to 74.5%), the NO level (from 77.1% to 94.4%), and the constitutive NOS activity (from 35.1% to 62.5%). These results indicate that pyrogallol decreased endothelium-dependent vasorelaxation in rat aortas via oxidative stress, which was markedly attenuated by apigenin. This may be mediated by weakening the oxidative stress and the NO reduction. (C) 2009 Elsevier B.V. All rights reserved.