Oral administration of a nitric oxide synthase inhibitor enhances de novo mammalian angiogenesis mediated by TNF-alpha, saline and mast-cell secretion.
In healthy adult rats, the test tissue that is used in the mesenteric-window angiogenesis assay is natively vascularized, lacks physiological angiogenesis, and is unperturbed by surgical intervention. Using the rat MWAA oral treatment with the nitric oxide (NO) synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) enhanced the angiogenic response (compared with controls receiving the inactive enantiomer D-NAME) following i.p. injections of (i) TNF-alpha at an approximate physiological dose, (ii) Compound 48/80, which is a highly selective secretagogue causing mast-cell secretion in situ and a very strong angiogenic response, and (iii) saline of a grade not made for infusion, causing a weak angiogenic response. Angiogenesis was assessed quantitatively using microscopic morphometry and image analysis in terms of objective variables recording the microvascular spatial extension, microvascular density, number and length of microvessel segments (extending between two successive branching points) and the degree of microvessel tortuosity. The data strongly suggest that endogenous NO inhibits all three mammalian angiogenesis reactions, although to a markedly different extent. Notably, the present data are virtually the opposite of those that have been reported from other mammalian angiogenesis models, the test tissues of which display deranged homeostasis, such as surgical intervention and/or ischemia.
Norrby
K
K
Department of Pathology, Institute of Laboratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. klas.norrby@path.gu.se
D000284:Administration, Oral; D000818:Animals; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008322:Mammals; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009389:Neovascularization, Pathologic; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D015430:Weight Gain; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D003189:p-Methoxy-N-methylphenethylamine; D012965:Sodium Chloride; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester