Lin J C, Song C W
University of Minnesota Medical School, Department of Therapeutic Radiology-Radiation Oncology, Minneapolis 55455.
Radiat Res. 1990 Nov;124(2):171-7.
Hydralazine is a peripheral vasodilator used as an antihypertensive agent. Hydralazine has been reported to potentiate tumor damage by hyperthermia as well as by hypoxic-cell-specific drugs through the reduction of tumor blood flow and pO2. In the present study, we investigated the changes in blood perfusion caused by hydralazine in S.C. RIF-1 tumors and normal tissues in C3H mice using the 86Rb uptake technique and laser Doppler flowmetry. The tumor blood flow was decreased significantly by an intravenous administration of 0.5-10.0 mg/kg hydralazine, as determined by both uptake of 86Rb and laser Doppler flowmetry. The tumor pO2 was also decreased significantly by the injection of hydralazine. On the other hand, the uptake of 86Rb was increased significantly in the skin and muscle by hydralazine. The changes seen in the skin and muscle after injection of hydralazine as assessed by laser Doppler flowmetry were similar to those assessed by uptake of 86Rb, indicating a significant increase in blood circulation in these tissues. Uptake of 86Rb remained unchanged in the kidney and decreased in the liver and spleen in the presence of hydralazine in a dose-dependent manner at 0.5-10.0 mg/kg. The decline in uptake of 86Rb in normal tissues strongly suggests that hydralazine decreases the blood flow in these normal tissues. Thus the recent proposal to use hydralazine to increase the antitumor activity of heat or certain drugs needs to be reexamined.
肼屈嗪是一种用作抗高血压药物的外周血管扩张剂。据报道，肼屈嗪可通过减少肿瘤血流和氧分压，增强热疗以及缺氧细胞特异性药物对肿瘤的损伤作用。在本研究中，我们使用⁸⁶Rb摄取技术和激光多普勒血流仪，研究了肼屈嗪对C3H小鼠皮下RIF-1肿瘤和正常组织血流灌注的影响。静脉注射0.5 - 10.0mg/kg肼屈嗪后，通过⁸⁶Rb摄取和激光多普勒血流仪测定，肿瘤血流显著减少。注射肼屈嗪后，肿瘤的氧分压也显著降低。另一方面，肼屈嗪使皮肤和肌肉中的⁸⁶Rb摄取显著增加。激光多普勒血流仪评估的注射肼屈嗪后皮肤和肌肉的变化与⁸⁶Rb摄取评估的结果相似，表明这些组织中的血液循环显著增加。在0.5 - 10.0mg/kg剂量的肼屈嗪作用下，肾脏中的⁸⁶Rb摄取保持不变，肝脏和脾脏中的⁸⁶Rb摄取则呈剂量依赖性下降。正常组织中⁸⁶Rb摄取的下降强烈表明肼屈嗪减少了这些正常组织的血流。因此，最近关于使用肼屈嗪来增强热疗或某些药物抗肿瘤活性的提议需要重新审视。
