Histological evidence for nonperfused vasculature in a murine tumor following hydralazine administration.
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.
Trotter
M J
MJ
Medical Biophysics Unit, B.C. Cancer Research Centre, Vancouver, Canada.
Acker
B D
BD
Chaplin
D J
DJ
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply*; D004909:Erythrocyte Indices; D005260:Female; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D009374:Neoplasms, Experimental / Q000098:blood supply*
D006830:Hydralazine