The effect of a
calcium antagonist and a physiologic
amine on
tumor and muscle perfusion was investigated with the aim of improving the preconditions for external
hyperthermia treatment of
cancer.
Nisoldipine (0.04-4.0 mg/kg) and 5-hydroxy
tryptamine (5-HT) (0.2-8.0 mg/kg) were administered i.p. in Sprague-Dawley rats bearing Walker 256
carcinoma,
Yoshida sarcoma, or a homologous
tumor transplant derived from a spontaneous
leiomyosarcoma of the uterus. At the maximum dosage used,
nisoldipine injection caused a decrease of the regional washout rate of
Xenon-133 of 63 +/- 8% (SEM) in the Walker
carcinoma and an increase of 80 +/- 41% in the muscle of the hind leg.
5-HT (8 mg/kg) caused a drop of 79 +/- 29% in the Walker
carcinoma and only a slight fall of the washout rate in muscle of 14 +/- 4.8%.
Tumor-to-muscle uptake ratios of 11C-butanol fell from 5.63 +/- 1.98 to 3.32 +/- 1.21, and from 5.3 +/- 0.56 to 2.98 +/- 0.30, after injection of 0.2 mg/kg
nisoldipine and 4 mg/kg
5-HT, respectively. Similar reaction patterns and percentage changes were observed in different
tumor lines at constant doses of 0.2 mg/kg
nisoldipine and 4 mg/kg
5-HT. Both drugs representing two different rationales of vasomotor action were able to reduce blood flow specifically in transplanted
tumors;
nisoldipine increased muscle blood flow and decreased arterial blood pressure, whereas
5-HT acted without substantial systemic effects.