药理学系知识库

This study was designed to determine whether the relaxant effect of apigenin was endothelium dependent and to examine the possible antiproliferative effect of apigenin. Apigenin relaxed the phenylephrine-precontracted endothelium-intact aortic rings with IC50 value of 3.7+/-0.5 muM and removal of a functional endothelium significantly attenuated this relaxation (IC50 = 8.2+/-0.9 muM). However, apigenin did not affect the 0.1 muM phorbol 12,13-dibutyrate-induced contraction (IC50 = 34.6 +/- 1.2 muM) within the concentration range that relaxed the phenylephrine-contracted arteries, suggesting that apigenin did not influence protein kinase C-mediated contractile mechanisms in rat aorta. Pretreatment of apigenin significantly potentiated the relaxant effect of acetylcholine on phenylephrine-induced contraction. Pretreatment with N-G-nitro-L-arginine methyl ester (L-NAME) or methylene blue reduced the relaxant effect of apigenin. Apigenin (10 muM) increased the guanosine 3′,5′-cyclic monophosphate (cGMP) content of endothelium-intact tissues. Pretreatment with L-NAME (100 muM) or removal of endothelium significantly suppressed the effect of apigenin on cGMP production. In addition, apigenin significantly inhibited [H-3]thymidine incorporation into DNA of primary cultured rat aortic smooth muscle cell in a dose-dependent manner. These findings suggest that besides influx and release of Ca2+, nitric oxide (NO) and cGMP may account for the apigenin-induced endothelium-dependent relaxation and hypotensive activity. Both vasorelaxant and antiproliferative activities may contribute to a benefit of apigenin in the vascular system. (C) 2002 Elsevier Science Inc. All rights reserved.