Vasorelaxant effect of euxanthone in the rat thoracic aorta

Abstract

This study was undertaken to investigate the effect of euxanthone on isolated rat thoracic aorta. Euxanthone concentration-dependently relaxed high K +-induced sustained contractions with IC 50 values of 32.28 ± 1.73 μM and this inhibition was antagonized by increasing the Ca 2+ concentration in the medium. These results indicated that euxanthone may have calcium antagonistic property. Euxanthone also relaxed norepinephrine (NE)-induced sustained contractions with IC 50 values of 32.50 ± 2.15 μM and this relaxant effect was unaffected by the removal of endothelium or by the presence of propranolol, indomethacin, glibenclamide or N ω-nitro- l-arginine. Moreover, euxanthone inhibited both the phasic and tonic contractions induced by NE in a concentration-dependent manner and showed more potent inhibition on phasic contraction ( P < 0.01). Pre-treatment with euxanthone inhibited vascular contraction induced by phorbol 12, 13-dibutyrate (PDBu), a protein kinase C (PKC) agonist, in either the presence or absence of Ca 2+ in the solution with IC 50 values of 20.15 ± 1.56 and 18.30 ± 1.62 μM, respectively. However, when the tissues were treated with euxanthone after the PDBu-induced contraction had reached a steady state, the tension was not affected by euxanthone. This study also showed that the inhibitory effect of pre-treatment of euxanthone was more potent than the post-treatment after the tension had reached a steady state. These results suggested that the vasorelaxation of euxanthone may be through multiple pathways involved PKC-mediated signal pathway and calcium-independent pathway besides the direct inhibition of calcium influx and its vasorelaxant effect is more active on calcium-independent pathway and more sensitive to the initial stage of contraction.