Dose-dependent effects of hydralazine on microcirculatory function and hyperthermic response of murine FSall tumors

Cancer Res. 1990 Jan 1;50(1):15-9.

Abstract

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 micrograms/g i.p. HYD, the tumor showing a transient increase in flow and the skin remaining almost stable. At 1.0 micrograms/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 micrograms/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 degrees C for 15, 30, or 60 min). Tumor growth was measured daily and compared to controls (HT without hydralazine). Hydralazine at 0.25 micrograms/g i.p. did not affect heat induced growth delay. At 1.0 micrograms/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 micrograms/g i.p. increased growth delay for all heat doses (P less than 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Female
  • Fibrosarcoma / blood supply
  • Fibrosarcoma / pathology
  • Fibrosarcoma / physiopathology*
  • Heart Rate / drug effects
  • Hydralazine / pharmacology*
  • Hyperthermia, Induced*
  • Lasers
  • Male
  • Mice
  • Mice, Inbred C3H
  • Microcirculation / drug effects
  • Microcirculation / physiopathology
  • Regional Blood Flow / drug effects
  • Sarcoma, Experimental / physiopathology*

Substances

  • Hydralazine