Tanda S, Hori K, Saito S, Zhang Q H, Li H C, Suzuki M
Department of Tumor Microcirculation, Tohoku University, Sendai.
Jpn J Cancer Res. 1994 May;85(5):556-62. doi: 10.1111/j.1349-7006.1994.tb02395.x.
To determine the effects of intravenous administration of dopamine hydrochloride (DA) on tumor blood flow (TBF), we measured the blood flow of normal subcutaneous tissue and subcutaneous tumor (LY-80, a variant of Yoshida sarcoma) in enflurane-anesthetized male Donryu rats using a hydrogen clearance method. Measurements were made before and during intravenous infusion of DA at a rate of 5 micrograms/kg/min, while recording the mean arterial blood pressure of the rats. Under mild hypertension induced by DA, the blood flow of normal subcutis decreased and TBF increased significantly. SCH-23390, an antagonist of the DA1 receptor, inhibited the enhancement of TBF by DA; while domperidone, an antagonist of the DA2 receptor, did not modify the effects of DA. In experimental chemotherapy against the tumor using adriamycin (ADM) 5 mg/kg i.v., only the combination of DA and ADM significantly inhibited the tumor growth. Moreover, DA reduced the weight loss caused by ADM. These results indicate that DA could have a role in increasing TBF and possibly enhance drug delivery to tumors. Moreover, it appears that the DA1 receptor contributes, at least in part, to the enhanced blood flow in rat subcutaneous tumor following DA administration.
为了确定静脉注射盐酸多巴胺（DA）对肿瘤血流（TBF）的影响，我们使用氢清除法，在恩氟烷麻醉的雄性唐利大鼠中测量了正常皮下组织和皮下肿瘤（LY-80，吉田肉瘤变种）的血流。在以5微克/千克/分钟的速率静脉输注DA之前和期间进行测量，同时记录大鼠的平均动脉血压。在DA诱导的轻度高血压下，正常皮下组织的血流减少，而TBF显著增加。DA1受体拮抗剂SCH-23390抑制了DA对TBF的增强作用；而DA2受体拮抗剂多潘立酮则未改变DA的作用。在使用阿霉素（ADM）5毫克/千克静脉注射进行肿瘤实验化疗时，只有DA与ADM联合使用能显著抑制肿瘤生长。此外，DA减轻了ADM引起的体重减轻。这些结果表明，DA可能在增加TBF以及可能增强药物向肿瘤的递送方面发挥作用。此外，似乎DA1受体至少部分地促成了DA给药后大鼠皮下肿瘤血流的增加。
