Pharmacological modification of tumor blood flow: Lack of correlation between alteration of mean arterial blood pressure and changes in tumor perfusion

Abstract

The correlation between mean arterial blood pressure (MABP) and vascular perfusion in SCC-VII/St tumors in mice was compared following administration of three vasoactive drugs: flavone acetic acid (200 mg/kg), hydralazine (5 mg/kg), or nicotinamide (500, 750, and 1000 mg/kg). MABP was measured by the direct method in unanesthetized, unrestrained mice bearing a carotid catheter. Vascular perfusion of the tumor was measured using the 86RbCl extraction method. Body temperature was maintained at 36° to 37°C after drug administration when necessary. All three drugs reduced MABP from a control value of 125 ± 2 (s.e.) mm Hg in mice without tumors. Flavone acetic acid at this dose had the least effect on blood pressure, with a minimum of 86% of control values at 10 to 20 min, and a return to control values by 1 hr. However, it produced a profound reduction in tumor perfusion that lasted more than 48 hr. Hydralazine and nicotinamide reduced blood pressure to minima between 55% and 69% of control values within 30 min, followed by a gradual return toward control values by about 8 hr. The reduction in tumor perfusion by hydralazine paralleled its effect on blood pressure. However, nicotinamide produced a transitory, although not statistically significant, increase in tumor perfusion at the highest dose given. These data demonstrate that tumor blood flow modification by drugs is not necessarily the result of changes in MABP, and blood pressure changes alone do not inevitably lead to changes in tumor perfusion.