EFFECT OF HYDRALAZINE ON THE BLOOD-FLOW IN TUMORS AND NORMAL-TISSUES IN RATS

The effects of hydralazine on the blood flow in various normal tissues and R3230 Ac adenocarcinomas grown in different sites in rats were studied. Tumors were induced in the kidney, liver, and flank (s.c.) by injection of small pieces of tumors. Tumors were also induced in small intestine, cecum, and mesentery by intraperitoneal injection of finely minced tumor tissue. The blood flow and cardiac output were measured by radioactive microsphere method. An intra-arterial injection of hydralazine at 2.5-10.0 mg/kg significantly reduced the blood flow in most normal tissues, whereas it markedly increased the blood flow in muscle. The blood flow in the brain and testes remained unchanged. The blood flow in the tumors varied depending on the tumor site and was markedly smaller than the blood flow in the host normal tissues in which the tumors grew. The blood flow in tumors decreased significantly upon injection of hydralazine except in the tumors grown in the liver, where the blood flow remained unchanged. The hydralazine injection slightly increased cardiac output and markedly decreased blood pressure. It appeared that the decreases in blood flow by hydralazine in the tumors and most normal tissues were caused mainly by diversion of blood to muscle, resulting in a marked increase in the muscle blood flow without a similar concomitant increase in cardiac output. The results obtained in the present study indicate that hydralazine may be useful for improving the efficacy of hyperthermia or for enhancing the toxicity of hypoxic cell specific bioreductive drugs in treating the tumors grown in skeletal muscle. However, the significant decline in blood flow in most normal tissues may pose potential problems in the use of hydralazine to enhance the effect of hyperthermia or bioreductive drugs on tumors grown in normal tissues other than muscle.