MAST-CELL HISTAMINE IS ANGIOGENIC THROUGH RECEPTORS FOR HISTAMINE(1) AND HISTAMINE(2)

The activation of mast-cells in situ induces angiogenesis in normally vascularized, adult mammalian tissue. Since the secreting mast-cell ch aracteristically releases histamine, we studied the possible role of h istamine in the outcome of mast-cell mediated angiogenesis using the r at mesenteric window assay. One H-1-receptor antagonist, bromphenirami ne maleate (BPA), and one H-2-receptor antagonist, metiamide, were sep arately administered systemically (s.c.) at non-toxic doses during the period of angiogenesis induction. Angiogenesis was effected by i.p. i njections of the mast-cell secretagogue compound 48/80 for 5 consecuti ve days. The animals were killed 14 days after the start of the i.p. a nd s.c. treatment, close to the middle of the expanding angiogenic pha se of the angiogenic reaction studied. Angiogenesis was quantified in terms of (a) the number of vessel profiles per unit tissue length (No/ UL), which reflects mainly the degree of branching and/or tortuosity, (b) the relative vascularized area (VA), which is a measure of spatial extension, and (c) the vascular density (VD), a measure of vessel den sity per unit area of vascularized tissue. Whereas BPA significantly s uppressed No/UL, metiamide significantly reduced No/UL and VD in stati stical terms suggesting that endogenous mast-cell histamine is angioge nic through both H-1- and H-2-receptors. This appears to be the first paper to report that the occupancy of H-2-receptors is angiogenic.