Effect of vasoactive drugs on tumour blood flow as determined by 2H nuclear magnetic resonance spectroscopy

Acta Oncol. 1995;34(3):367-71. doi: 10.3109/02841869509093991.

Abstract

A selective reduction in tumour blood flow (TBF) could enhance the effects of hyperthermia treatment and of drugs toxic to hypoxic cells. Vasodilator-induced changes in TBF were monitored in transplanted rat fibrosarcomas by non-invasively measuring the uptake of D2O using 2H nuclear magnetic resonance spectroscopy. Hydralazine (1 or 5 mg kg-1) caused a large (45%) reduction in mean arterial blood pressure (MABP) and a 40-60% reduction in TBF. Low-dose hydralazine (0.1 mg kg-1) caused a 20% reduction in MABP but no significant change in TBF. The doses of prazosin (1 mg kg-1) and calcitonin-gene related peptide (CGRP, 1 nmol kg-1) which caused a 20% reduction in MABP led to a 50-60% reduction in TBF. These results demonstrate the advantage of prazosin and CGRP over hydralazine for the reduction of TBF despite a small hypotensive effect. CGRP may be the most suitable of these agents for clinical use because of its short physiological half-life.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects*
  • Body Water / metabolism
  • Calcitonin Gene-Related Peptide / pharmacology*
  • Cell Hypoxia
  • Deuterium
  • Deuterium Oxide
  • Dose-Response Relationship, Drug
  • Fibrosarcoma / blood supply*
  • Hydralazine / pharmacology*
  • Hyperthermia, Induced
  • Magnetic Resonance Spectroscopy / methods
  • Prazosin / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Regional Blood Flow / drug effects*
  • Time Factors

Substances

  • Hydralazine
  • Deuterium
  • Deuterium Oxide
  • Calcitonin Gene-Related Peptide
  • Prazosin