Abnormal response of tumor vasculature to vasoactive drugs

The effects of the vasoconstrictor phenylephrine and the vasodilator hydralazine on blood flow to tumor were studied and compared to those on blood flow to normal tissues in vivo. Regional blood flow and cardiac output were measured with the use of radioactive microspheres in 150- to 250-g inbred Harlan F344 rats bearing subcutaneous nodules of two types of transplantable carcinoma ("hard" and "soft") with microscopically different vascular patterns. Three groups of rats were treated with hydralazine, saline, or phenylephrine, and regional blood flow was determined at the time of maximum blood pressure response. Results were correlated with quantitative morphometric analysis of arteriolar and capillary wall thickness in tumor and normal tissue. Phenylephrine decreased and hydralazine increased normal tissue perfusion as indicated by cardiac output. Tumor blood flow remained low and was not significantly influenced by drug treatment, except for the phenylephrine effect on hard tumors. Histologic study of tumor vessel walls revealed an absence of smooth muscle capable of responding to the vasoactive drugs by constriction or dilation. Evidently, by their selective action on normal vessels, vasoactive drugs can change the ratio of tumor:normal tissue perfusion. In particular, the increase of normal tissue: tumor blood flow by vasodilator drugs may enhance the selectivity of local heat therapy.