Vasorelaxant effect of euxanthone in the rat thoracic aorta

This study was undertaken to investigate the effect of euxanthone on isolated rat thoracic aorta. Euxamhone concentration-dependently relaxed high K+-induced sustained contractions with IC50 values of 32.28 +/- 1.73 mu M and this inhibition was antagonized by increasing the Ca2+ concentration in the medium. These results indicated that euxanthone may have calcium antagonistic property. Euxanthone also relaxed norepinephrine (NE)induced sustained contractions with IC50 values of 32.50 +/- 2.15 mu M and this relaxant effect was unaffected by the removal of endothelium or by the presence of propranolol, indomethacin, glibenclamide or N-omega-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 Ca2+ in the solution with IC50 values of 20.15 +/- 1.56 and 18.30 +/- 1.62 mu M, 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. (c) 2006 Elsevier Inc. All rights reserved.