The antineoplastic agent paclitaxel (Taxol) increases contractile activity in human saphenous veins and human mammary arteries.
Effects of the antineoplastic agent paclitaxel (Taxol) were studied on contractions 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 the left of dose-response curves. Paclitaxel 1 microM decreased ED50 (in microM) 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 microM also significantly increased the peak force of contractions elicited by endothelin-1 0.01 microM 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.
Gómez-Alvis
A
A
Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Argentina.
Rinaldi
G
G
Rebolledo
A
A
Milesi
V
V
Sanz
N
N
Tommasi
J
J
Grassi de Gende
A
A
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D006801:Humans; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology*; D012501:Saphenous Vein / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology
D000972:Antineoplastic Agents, Phytogenic; D019332:Endothelin-1; D012701:Serotonin; D017239:Paclitaxel; D009638:Norepinephrine