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Effect of hydralazine on the blood flow in tumors and normal tissues in rats
1University of Minnesota Medical School, Department of Therapeutic Radiology, Minneapolis 55455.
Abstract:
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.
Insights
Hydralazine reduces blood flow in most normal tissues and tumors, but increases it in muscle. This suggests potential use in muscle tumors but cautions against use in other normal tissues.
Area of Science:
- Pharmacology
- Oncology
- Physiology
Background:
- Hydralazine is a vasodilator.
- Tumor blood flow is heterogeneous and often lower than in normal tissues.
- Understanding drug effects on tumor and normal tissue perfusion is crucial for cancer therapy.
Purpose of the Study:
- To investigate the effects of hydralazine on blood flow in various normal tissues and R3230 Ac adenocarcinomas in rats.
- To determine if hydralazine alters tumor perfusion differently based on tumor site.
- To evaluate the potential of hydralazine in combination cancer therapies.
Main Methods:
- Rats bearing R3230 Ac adenocarcinomas in kidney, liver, flank, small intestine, cecum, and mesentery were used.
- Blood flow and cardiac output were measured using the radioactive microsphere method.
- Hydralazine was administered via intra-arterial injection at doses of 2.5-10.0 mg/kg.
Main Results:
- Hydralazine significantly reduced blood flow in most normal tissues but increased it in muscle.
- Brain and testes blood flow remained unchanged.
- Tumor blood flow varied by site, was generally lower than host tissue, and decreased with hydralazine, except in liver tumors.
Conclusions:
- Hydralazine-induced blood flow reduction in tumors and normal tissues may be due to diversion to muscle.
- Hydralazine could enhance hyperthermia or bioreductive drug efficacy in skeletal muscle tumors.
- Potential adverse effects due to reduced blood flow in other normal tissues warrant caution.