Tokuda K
Hokkaido Igaku Zasshi. 1986 Jul;61(4):612-20.
Blood flow of transplanted intracerebral rat gliomas was measured before and after a constant I.V. infusion of angiotensin II-induced arterial hypertension using hydrogen clearance method. The brain tumor model was produced in syngeneic Wistar-King-Aptekman male rats by stereotaxic inoculation of ethylnitrosourea-induced glioma cells (KEG-1). Induced hypertension by angiotensin II infusion resulted in a significant increase in tumor blood flow compared with control levels (P less than 0.001). In addition, the therapeutic effect of administration of 3-[(4-amino-2-methyl-5-pyrimidinyl) ethyl] -1-(2-chloroethyl)-1-nitrosourea (ACNU) during angiotensin II-induced hypertension was evaluated. At 12 days after implantation, tumor-bearing rats were administrated angiotensin II as the mean blood pressure reached 150 mmHg, followed by ACNU injection, maintained the same blood pressure for 20 minutes. ACNU with induced hypertension group showed a median survival time of 27.0 days, which was significantly (P less than 0.02) longer than that of ACNU alone (22.0 days). It is therefore suggested that chemotherapy with angiotensin II-induced hypertension has a enhancing effect on chemotherapy for improving the drug delivery to tumor tissue by a increased tumor blood flow.
采用氢清除法，在静脉持续输注血管紧张素II诱导动脉高血压前后，测量移植到大鼠脑内的胶质瘤的血流情况。通过立体定位接种乙基亚硝基脲诱导的胶质瘤细胞（KEG-1），在同基因的Wistar-King-Aptekman雄性大鼠中建立脑肿瘤模型。与对照水平相比，输注血管紧张素II诱导的高血压导致肿瘤血流显著增加（P<0.001）。此外，还评估了在血管紧张素II诱导的高血压期间给予3-[(4-氨基-2-甲基-5-嘧啶基)乙基]-1-(2-氯乙基)-1-亚硝基脲（ACNU）的治疗效果。植入后12天，当荷瘤大鼠平均血压达到150 mmHg时给予血管紧张素II，随后注射ACNU，并维持相同血压20分钟。ACNU联合诱导高血压组的中位生存时间为27.0天，显著长于单独使用ACNU组（22.0天）（P<0.02）。因此，提示血管紧张素II诱导高血压化疗通过增加肿瘤血流，对改善肿瘤组织药物递送的化疗具有增强作用。
