Action of polygodial on agonist-induced contractions of the rat portal vein in vitro

This study investigated the vasorelaxant action of the sesquiterpene polygodial, isolated from the bark of Drymis winteri, on rat portal vein in vitro, contracted by various agonists. Polygodial (21-342 mu M) preincubated 20 min before, produced graded antagonism of the contractile responses caused by bradykinin, endothelin-1, noradrenaline, the stable analogue of thromboxane A(2) U46619, substance P, neurokinin B, and senktide (an NK3-selective agonist). Polygodial, at the same concentration, also produced graded inhibition of the contractile response induced by potassium chloride and by phorbol ester. At the median inhibitory concentration (IC50) level, polygodial was similar to 114; to 177-fold more active in inhibiting mediated contractions to senktide and phorbol ester. When assessed in the tonic contraction induced by endothelin-1 (0.5 nM) or by phorbol (3 mu M), polygodial (0.1-100 mu M) produced concentration-dependent relaxation, with maximal inhibition (E-max) of 62 +/- 2% and 100%, respectively. Finally, polygodial(0.1-100 mu M) inhibited the rhythmic spontaneous contractions of the rat portal vein (E-max of 75 +/- 2%), Taken together, these results suggest that the vasorelaxant actions caused by polygodial in rat portal vein an, at least in part, associated with inhibition of calcium influx through voltage-sensitive channels and interaction with protein kinase C-dependent mechanisms. In addition, these data confirm and extend our previous suggestion that polygodial preferentially antagonizes tachykinin-mediated contraction, especially the NK3-mediated responses.