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Protamine and mast-cell-mediated angiogenesis in the rat.

Different doses of protamine sulphate (PS) given s.c. (at 12-h intervals) were tested for signs of non-specific toxicity measured as effect on body weight and small-gut proliferation as well as on mast-cell secretion and mast-cell-mediated mitogenesis in the mesenteric windows following i.p. injection of Compound 48/80, a potent mast cell secretagogue, in normal rats. In a non-toxic dose range, the effect of PS on mast-cell-mediated angiogenesis, effected by 48/80, was quantified as the number of vessels per mm of mesenteric window in histological sections at x 400. No intelligible dose-effect relationship was discernible between the dose of PS given and the effect on angiogenesis. Only in a tight interval, at 40 mg PS/kg but not at 20 or 60 mg PS/kg, was the angiogenesis statistically significantly suppressed. Hence, it was concluded that PS can be angiostatic but does not exert a more general angiostatic effect in the autogenous systems used.