Histological evidence for nonperfused vasculature in a murine tumor following hydralazine administration

Abstract

The effect of the vasodilator hydralazine on tumor vascular function has been evaluated in C3H/He mice bearing subcutaneously implanted SCCVII squamous cell carcinoma. Changes in microregional perfusion following hydralazine administration were observed using a double fluorescent staining technique. Hydralazine-induced alterations in tumor blood flow were measured using laser Doppler flowmetry. The results obtained indicate that hydralazine causes a dose-dependent reduction in functional tumor vasculature implying complete flow stasis and/or vascular collapse in some vessels. Fifteen minutes after a dose of 10 mg/kg intravenously, perfusion in 36 +/- 5% (SEM) of tumor vessels was completely abolished. In addition to cessation of perfusion in individual vessels, hydralazine eliminated flow in large patches of vasculature distributed non-uniformly throughout the tumor. Hydralazine (10 mg/kg i.v.) resulted in a 67 +/- 5% (SEM) reduction in tumor red blood cell (RBC) flow as measured by laser Doppler techniques. The mean number of moving red blood cells declined by 35 +/- 8%, suggesting a reduction in microvascular volume. These results support the hypothesis that following hydralazine administration, perfusion stops completely in some blood vessels probably as a result of vascular collapse or flow stasis.