Effects of Hydralazine-Induced Vasodilation on the Energy Metabolism of Murine Tumors Studied by In Vivo31P-Nuclear Magnetic Resonance Spectroscopy1

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Abstract
The effects of hydralazine on tumor energy metabolism and on some cardiovascular parameters were measured. Tumor energy metabolism was studied in C3HF/Sed mice with iso-transplants of a spontaneous murine fibrosarcoma (FSaII, α100 mm3 in volume) and31P-NMR. Cardiovascular Parameters were measured in anesthetized C3Hf/Sed mice via intracarotid catheter. Hydralazine doses of 0.25 mg/kg given ip caused an increase of the phosphocreatine to in-organic phosphate ratio (PCr: P1) in 5 of 6 animals. These doses had minimal effects on mean arterial blood pressure, though there may have been an increased cardiac output due to a decreased afterload. Hydralazine doses≧2.0 mg/kg given ip were associated with a decrease in PCr, nucleotide triphosphate, and pH, and an increase in P1 (P<.01 for control vs. 10mg hydradazine/kg). This substantial decrease in high-energy phosphates was associated with a pronounced decrement in mean arterial blood pressure. These findings provide a rational basis for the study in experimental systems of hydralazine-induced enhancement of cell killing by hyperthermia and by agents toxic to hypoxic cells. Further, these results can be taken as a sign that hydralazine should be used with care in patients under going radiation treatment. [J Natl Cancer Inst 1988;80:745–750]