VASODILATORY ACTION MECHANISMS OF APIGENIN ISOLATED FROM APIUM-GRAVEOLENS IN RAT THORACIC AORTA

The effect of apigenin, isolated from Apium graveolens, on the contraction of rat thoracic aorta was studied. Apigenin inhibited the contraction of aortic rings caused by cumulative concentrations of calcium (0.03-3 mM) in high potassium (60 mM) medium, with an IC50 of about 48-mu-M. After pretreatment it also inhibited norepinephrine (NE, 3-mu-M)-induced phasic and tonic contraction in a concentration (35-140-mu-M)-dependent manner with an IC50 of 63-mu-M. At the plateau of NE-induced tonic contraction, addition of apigenin caused relaxation. This relaxing effect of apigenin was not antagonized by indomethacin (20-mu-M) or methylene blue (50-mu-M), and still existed in endothelial denuded rat aorta or in the presence of nifedipine (2-100-mu-M). Neither cAMP nor cGMP levels were changed by apigenin. Both the formation of inositol monophosphate caused by NE and the phasic contraction induced by caffeine in the Ca2+-free solution were unaffected by apigenin. Ca-45(2+) influx caused by either NE or K+ was inhibited by apigenin concentration-dependently. It is concluded that apigenin relaxes rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels.