The antineoplastic agent paclitaxel (Taxol (R)) increases contractile activity in human saphenous veins and human mammary arteries

Effects of the antineoplastic agent paclitaxel (Taxol(R)) were studied on c ontractions of isolated human saphenous vein (HSV) and mammary artery (HMA) . Peak force developed by vascular segments with cumulative concentrations of physiologic agonists was enhanced by paclitaxel, producing a shift to th e left of dose-response curves. Paclitaxel 1 mu M decreased ED50 (in mu M) for norepinephrine from 1.01 +/- 0.24 to 0.20 +/- 0.06 (n = 16, p < 0.05) i n HSV and from 1.30 +/- 0.30 to 0.51 +/- 0.21 (n = 15, p < 0.05) in HMA and for 5-hydroxytriptamine from 0.64 +/- 0.19 to 0.21 +/- 0.07 (n = 20, p < 0 .05) in HSV. Paclitaxel 1 mu M also significantly increased the peak force of contractions elicited by endothelin-1 0.01 mu M in HSV. In contrast, it did not affect contractions evoked by KCl 80 mM. These results show that pa clitaxel produces a hyperreactivity in human vessels challenged by physiolo gic agonists, which suggests that administration of paclitaxel to patients could augment peripheral resistance and increase blood pressure.