Effects of hydralazine-induced vasodilation on the energy metabolism of murine tumors studied by in vivo 31P-nuclear magnetic resonance spectroscopy.
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 isotransplants of a spontaneous murine fibrosarcoma (FSaII, congruent to 100 mm3 in volume) and 31P-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 inorganic phosphate ratio (PCr: Pi) 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 greater than or equal to 2.0 mg/kg given ip were associated with a decrease in PCr, nucleotide triphosphate, and pH, and an increase in Pi (P less than .01 for control vs. 10 mg hydralazine/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 undergoing radiation treatment.
Okunieff
P
P
Department of Radiation Medicine, Massachusetts General Hospital, Boston 02114.
Kallinowski
F
F
Vaupel
P
P
Neuringer
L J
LJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism; D005260:Female; D006830:Hydralazine / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism; D010710:Phosphates / Q000097:blood; D010725:Phosphocreatine / Q000097:blood; D014664:Vasodilation
D010710:Phosphates; D010725:Phosphocreatine; D006830:Hydralazine