Modification of the 31P magnetic resonance spectra of a rat tumour using vasodilators and its relationship to hypotension.
The effects of different doses of hydralazine and prostacyclin on the 31P magnetic resonance spectra of the LBDS1 fibrosarcoma were investigated and related to their effects on mean arterial blood pressure (MABP) and heart rate. The effect of reducing MABP by bleeding the animals, via the tail artery, was also investigated. Tumour spectral changes following high dose drug treatment (an increase in inorganic phosphate, a reduction in nucleotide triphosphates and a reduction in pH) were consistent with nutrient deprivation. These changes were dose dependent. Changes in MABP and heart rate were consistent with vasodilatation in normal tissues. However, for the same fall in MABP, hydralazine produced a greater rise in tumour inorganic phosphate (Pi) and a greater fall in tumour pH than did prostacyclin. Controlled bleeding was effective in reducing MABP. It also reduced tumour pH but had no significant effect on tumour Pi. The clinical application of the two drugs for reducing tumour blood flow and pH for therapy is likely to be limited by the large degree of hypotension necessary to produce an effect. The differential effect of the two drugs for the same fall in MABP may be related to different degrees of direct tumour vasodilatation or to a direct effect of hydralazine on tumour energy metabolism. The observation that controlled bleeding does not change tumour Pi is further evidence indicating that the degree of arterial hypotension is not the sole factor in determining tumour energy status.
Tozer
G M
GM
Medical Research Council Cyclotron Unit, Hammersmith Hospital, London, UK.
Maxwell
R J
RJ
Griffiths
J R
JR
Pham
P
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism*; D010710:Phosphates / Q000032:analysis; D010725:Phosphocreatine / Q000032:analysis; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology*
D010710:Phosphates; D014665:Vasodilator Agents; D010725:Phosphocreatine; D006830:Hydralazine; D011464:Epoprostenol