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Dose-dependent Effects of Hydralazine on Microcirculatory Function and Hyperthermic Response of Murine FSall Tumors¹

Department of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

The effects of the vasodilator hydralazine (HYD) on microcirculatory function and hyperthermic response were studied in early generation isotransplants of a spontaneous C3Hf/Sed mouse fibrosarcoma (FSall). Red blood cell flux (RBC flux) in superficial tumor regions was assessed using laser Doppler flowmetry. A differential microcirculatory response was seen between tumor and normal skin after 0.25 µg/g i.p. HYD, the tumor showing a transient increase in flow and the skin remaining almost stable. At 1.0 µg/g i.p., the differential response continued, this time with a transient fall in tumor blood flow but again no change in skin flow. High dose hydralazine (10.0 µg/g i.p.) was associated with a dramatic and prolonged decrease in tumor blood flow but a lesser and only transient decline in skin flow.

Identical doses of hydralazine were given 30 min prior to heat treatment (43.5°C for 15, 30, or 60 min). Tumor growth was measured daily and compared to controls (HT without hydralazine). Hydralazine at 0.25 µg/g i.p. did not affect heat induced growth delay. At 1.0 µg/g i.p., it significantly increased growth delay upon heat exposures of 15 min, but not after 30 or 60 min HT. Hydralazine at 10 µg/g i.p. increased growth delay for all heat doses (P < 0.05). Hydralazine alone had no influence on growth delay of sham-heated tumors. The results obtained clearly indicate that tumor and normal tissues have microcirculatory differences in the time-course, degree and/or direction of response after hydralazine, and that hydralazine has potential for increasing the response of tumor to HT.

¹ This work was supported in part by NIH Grants CA48096 and CA13311, by the ACS Career Development Award, and by the Deutsche Forschungsgemeinschaft Postdoctoral Fellowship.

² To whom requests for reprints should be addressed, at Department of Radiation Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114.

Received 1/30/89. Revised 5/18/89. Revised 9/26/89. Accepted 10/ 3/89.