EFFECT OF VASOACTIVE DRUGS ON TUMOR BLOOD-FLOW AS DETERMINED BY H-2 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

A selective reduction in tumour blood flow (TBF) could enhance the eff ects of hyperthermia treatment and of drugs toxic to hypoxic cells. Va sodilator-induced changes in TBF were monitored in transplanted rat fi brosarcomas by non-invasively measuring the uptake of D2O using H-2 nu clear magnetic resonance spectroscopy. Hydralazine (1 or 5 mg kg(-1)) caused a large (45%) reduction in mean arterial blood pressure (MABP) and a 40-60% reduction in TBF. Low-dose hydralazine (0.1 mg kg(-1)) ca used a 20% reduction in MABP but no significant change in TBF. The dos es of prazosin (1 mg kg(-1)) and calcitonin-gene related peptide (CGRP , 1 nmol kg(-1)) which caused a 20% reduction in MABP led to a 50-60% reduction in TBF. These results demonstrate the advantage of prazosin and CGRP over hydralazine for the reduction of TBF despite a small hyp otensive effect. CGRP may be the most suitable of these agents for cli nical use because of its short physiological half-life.