The Antineoplastic Agent Paclitaxel (Taxol®) Increases Contractile Activity in Human Saphenous Veins and Human Mammary Arteries

Abstract

Effects of the antineoplastic agent paclitaxel (Taxol®) were studied on contractions of isolated human saphenom 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 the left of dose-response curves. Paclitaxel 1 μM decreased ED₅₀ (in μM) for norepinephrine from 1.01 ± 0.24 to 0.20 ± 0.06 (n = 16, p < 0.05) in 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 μM also significantly increased the peak force of contractions elicited by endothelin-1 0.01 μM in HSV. In contrast, it did not affect contractions evoked by KCl 80 mM. These results show that paclitaxel produces a hyperreactivity in human vessels challenged by physiologic agonists, which suggests that administration of paclitaxel to patients could augment peripheral resistance and increase blood pressure.