The proline analog L-azetidine-2-carboxylic acid modifies the neovascularization pattern by inhibiting branching or tortuosity and stimulating spatial expansion in the rat mesentery.

The L-proline analog L-azetidine-2-carboxylic acid, LACA, systemically inhibited autogenous mast-cell-mediated angiogenesis in normal rats. LACA was injected s.c. at a dose of 100 mg/kg/day and the angiogenic response was assessed in the mesenteric windows. Angiogenesis was induced by the i.p. injection of a highly-selective activator of the mast cells in situ. At these concentrations, LACA appeared to be non-toxic since it affected neither the physiologic body-weight gain nor the mast-cell secretory capacity in the test tissue. The LACA-treatment markedly reduced (p < or = 0.01) microvascular formation in terms of the number of vessels per unit length of tissue (No/mm) but, at the same time, tended to stimulate the spatial expansion of the newly-formed vasculature in terms of the vascularized area (VA). Since No/mm is a measure that reflects the degree of branching, the degree of tortuosity and VA, the findings suggest that LACA inhibited branching/tortuosity and simultaneously stimulated the spatial expansion of the new microvasculature. The difference in response to LACA in terms of No/mm and VA was highly statistically-significant (p < or = 0.0001). The fact that an agent may affect neovascular branching/tortuosity and spatial extension in a distinctly contradictory fashion has not been reported previously.