NO and de novo mammalian angiogenesis: further evidence that NO inhibits bFGF-induced angiogenesis while not influencing VEGF165-induced angiogenesis.
Using the non-surgical rat mesenteric window angiogenesis assay, we studied the systemic effect of (i) the nitric oxide (NO)-releasing vasodilator isosorbide-5-mononitrate (ISMN) and (ii) the NO-synthase inhibitor L-NAME on angiogenesis induced by the intraperitoneal injection of bFGF and VEGF165. The response was assessed objectively and quantitatively by microscopic morphometry and image analysis in terms of the vascularized area (VA; a measurement of microvessel spatial extension), the microvascular length (MVL; a composite measurement of microvessel density), the total microvascular length (TMVL=VA x MVL), the number of microvessel segments per unit tissue volume (No. MS), the length of the microvessel segments (Le. MS) and the degree of microvessel tortuosity (MVT). Additional architectural features of the network were assessed in terms of variables introduced here: the number of microvessel branching points per unit tissue volume (No. BP), the index of interconnecting microvessel loop formation (In. LF), the index of microvessel intersection (In. IS), the number of microvessel sprouts per unit tissue volume (No. SP) and their length (Le. SP). In bFGF-mediated angiogenesis, L-NAME significantly, augmented angiogenesis, whereas ISMN significantly inhibited angiogenesis. By contrast, neither L-NAME nor ISMN affected the angiogenic response to VEGF165.
Näslund
I
I
Department of Pathology, Sahlgrenska University Hospital, Göteborg University, Sweden.
Norrby
K
K
D000818:Animals; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000254:growth & development; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D008222:Lymphokines; D020030:Nitric Oxide Donors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate; D019331:NG-Nitroarginine Methyl Ester