Two potentially angiostatic factors, a steroid and L-azetidine-2-carboxylic acid, antagonize one another.
The proline analogue L-azetidine-2-carboxylic acid (LACA) systemically suppressed mast-cell-mediated angiogenesis, as measured by the rat mesenteric-window method. Dexamethasone and methylprednisolone at very low and non-toxic s.c. doses also somewhat inhibited the angiogenesis. Most interestingly, the co-administration of either of these steroids with LACA paradoxically stimulated angiogenesis. These findings suggest that in the future search for candidates for clinically-useful systemic angiostatic remedies, one may have to focus not only on the effect of individual drugs or agents, but also on the effect of such putative anti-angiogenic agents when co-administered. The fact that two potentially angiostatic agents can antagonize one another has not previously been reported.
Norrby
K
K
Department of Pathology, Sahlgren Hospital, Göteborg, Sweden.
Jakobsson
A
A
Nilsson
C L
CL
D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D003907:Dexamethasone / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D004359:Drug Therapy, Combination; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D008775:Methylprednisolone / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D001383:Azetidinecarboxylic Acid; D003907:Dexamethasone; D008775:Methylprednisolone