Influence of hydralazine administration on oxygenation in spontaneous and transplanted tumor models

Abstract

Purpose: To examine the effects of hydralazine on vascular perfusion and hypoxia in spontaneous vs. first generation and long-term transplanted murine tumor models. Methods and Materials: Total anatomic blood vessels were quantified using image analysis of CD31 stained frozen sections, perfused vessels by i.v. injection of fluorescent DiOC 7, and tumor hypoxia was measured using the EF5 hypoxia marker. KHT sarcomas, spontaneous mammary carcinomas, and first generation transplants of the spontaneous tumors were evaluated before and after i.p. administration of 5 mg/kg hydralazine. Results: Although anatomic and perfused vessel spacings were similar among untreated tumors, response to hydralazine varied widely among the three tumor models. In KHT tumors, perfused vessel numbers decreased significantly at 30 min post-hydralazine, then recovered somewhat by 60 min. First-generation transplants showed a less substantial decrease in perfused vessels following hydralazine, which tapered off slightly by 60 min. Finally, spontaneous tumors had only a modest decrease in perfused vessel numbers, with complete recovery at 60 min. Although response of individual tumors varied widely, overall hypoxic marker uptake was significantly increased in both KHT and first generation tumors, and slightly reduced in the spontaneous tumors. Conclusion: Response to hydralazine varies substantially between transplanted and spontaneous tumor models. Results suggest that increased tumor pressure may be a critical factor in tumor response to hydralazine, possibly explaining tumor volume dependent variations.