Evidence of specificity in the action of angiogenesis antagonists.
It is not known whether each type of angiogenesis reaction has a specific antiangiogenic mechanism and to what extent angiostatic agents can exert additional or synergistic effects. The objective of this study was to elucidate the way in which systemic angiostatic drug treatment by either one drug at a time or two in combination affects distinct angiogenesis reactions in one and the same vascular bed. The chemically unrelated drugs which were used were dexamethasone (DE) and ciclosporin A (CS) at nontoxic doses in the range used clinically. These drugs are known to act angiostatically in the rat. The rat mesenteric window angiogenesis assay was used to assess the systemic effect of DE, CS and DE plus CS in saline-mediated angiogenesis (SMA) and mast-cell-mediated angiogenesis (MCMA). Angiogenesis was quantified by microscopic and morphometric means, one variable being the number of vessel profiles per unit tissue length (No/UL), a measure related to the degree of microvascular branching and tortuosity. Whereas CS significantly suppressed No/UL in SMA without substantially affecting MCMA, DE plus CS significantly suppressed No/UL in MCMA, but, unexpectedly, somewhat increased No/UL in SMA. As compared with either drug given alone, the coadministration of the drugs clearly did not enhance the antiangiogenic effect in SMA. The drugs, whether alone or in combination specifically and selectively suppressed the angiogenesis reactions which were examined, thereby suggesting distinct antiangiogenic mechanisms in SMA and MCMA.
Norrby
K
K
Department of Pathology, University of Göteborg, Sahlgrenska University Hospital, Sweden.
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D008407:Mast Cells / Q000502:physiology; D008643:Mesentery / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D003189:p-Methoxy-N-methylphenethylamine; D012965:Sodium Chloride; D003907:Dexamethasone; D016572:Cyclosporine