Nitro-L-arginine methyl ester (0.15 μmol/paw) significantly reduced both bradykinin- and 5-hydroxytryptamine-induced rat paw oedema. At this dose, L-arginine (L-Arg), D-Arg and nitro-D-arginine methyl ester had no effect on the oedematogenic responses induced by these agents. Nitro-L-arginine methyl ester, nitro-D-arginine methyl ester, L-Arg, D-Arg L-arginine methyl ester and L-arginine ethyl ester, at the dose of 15 μmol/paw, significantly potentiated both bradykinin- and 5-hydroxytryptamine-induced oedema. This potentiation was not observed in animals treated with both mepyramine and methysergide or in animals chronically treated with compound 48/80. Nitro-L-arginine methyl ester (0.3-3 mM) and L-Arg (0.3-3 mM) released small amounts (<10%) of histamine from rat peritoneal mast cells when compared to compound 48/80-induced degranulation (>40%). Histamine release was quantified by radioimmunoassay since nitro-L-arginine methyl ester and L-Arg interfere with the fluorometric assay. The potentiation of paw oedema observed with higher doses of all arginine analogues is caused by in vivo mast cell degranulation and is probably due to the cationic charge of these substances. © 1994.2571-28793Antunes, Mariano, Cirino, Levi, De Nucci, Pharmacological characterization of polycation-induced rat hindpaw oedema (1990) Br. J. Pharmacol., 101, p. 986Antunes, Giraldelo, Cirino, De Nucci, Effects of NG-monomethyl-L-marginine and its D-enantiomer on rat hind-paw oedema (1992) Biology of Nitric Oxide — Physiological and Clinical Aspects, p. 264. , S. Moncada, M.A. Marletta, J.B. Hibbs, E.A. Higgs, Portland Press, LondonBult, Boeckxstaens, Pelckmans, Jordaens, Van Maercke, Herman, Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter (1990) Nature, 345, p. 346Burnett, Lowenstein, Bredt, Chang, Snyder, Nitric oxide: a physiologic mediator of penile erection (1992) Science, 257, p. 401Chiu, Burrall, Effects of interleukin 3 on the differentiation and histamine content of cultured bone marrow mast cells (1990) Agents Actions, 31, p. 197Desai, Sessa, Vane, Involvement of nitric oxide in the reflex relaxation of the stomach to accommodate food or fluid (1991) Nature, 351, p. 477Devillier, Drapeau, Renoux, Regoli, Role of the N-terminal arginine in the histamine-releasing activity of substance P, bradykinin and related peptides (1989) Eur. J. Pharmacol., 168, p. 53Di Rosa, Giroud, Willoughby, Studies of the mediators of the acute inflammatory response induced in rats in different sites by carrageenin and turpentine (1971) J. Pathol., 104, p. 15Enerback, Svensson, Isolation of rat peritoneal mast cells by centrifugation on density gradients of Percoll (1980) J. Immunol. Methods, 39, p. 135Ennis, Pearce, Weston, Some studies on the release of histamine from mast cells stimulated with polylysine (1980) Br. J. Pharmacol., 70, p. 329Furchgott, Zawadzki, The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine (1980) Nature, 288, p. 373Garthwaite, Charles, Chess-Williams, Endothelium-derived relaxing factor release on activation of NMDA receptors suggests a role as intercellular messenger in brain (1988) Nature, 336, p. 385Hibbs, Jr., Taintor, Vavrin, Rachlin, Nitric oxide: a cytotoxic activated macrophage effector molecule (1988) Biochem. Biophys. Res. Commun., 157, p. 87Hughes, Williams, Brain, Evidence that endogenous nitric oxide modulates oedema formation induced sustance P (1990) Eur. J. Pharmacol., 191, p. 481Ialenti, Ianaro, Moncada, Di Rosa, Modulation of acute inflammation by endogenous nitric oxide (1992) Eur. J. Pharmacol., 211, p. 177Ignarro, Buga, Wood, Byrns, Chaudhuri, Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide (1987) Proc. Natl. Acad. Sci. USA, 84, p. 9265Ishii, Chang, Kerwin, Huang, Murad, NG-NitroL-arginine: a potent inhibitor of EDRF formation (1990) Eur. J. Pharmacol., 176, p. 219Knowles, Palacios, Palmer, Moncada, Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase (1989) Proc. Natl. Acad. Sci. USA, 86, p. 5159Li, Rand, Evidence for a role of nitric oxide in the neurotransmitter system mediating relaxation of the rat anococcygeus muscle (1989) Clin. Exp. Pharmacol. Physiol., 16, p. 933Li, Rand, Nitric oxide and vasoactive intestinal polypeptide mediate non-adrenergic, non-cholinergic inhibitory transmission to smooth muscle of the rat gastric fundus (1990) Eur. J. Pharmacol., 191, p. 303Lykke, Cummings, Inflammation in healing. I. Time course and mediation of exudation in wound healing in the rat (1969) Br. J. Exp. Pathol., 50, p. 309Masini, Mannaioni, Pistelli, Salvemini, Vane, Impairment of the L-arginine-nitric oxide pathway in mast cells from spontaneously hypertensive rats (1991) Biochemical and Biophysical Research Communications, 177, p. 1178Mayhan, Role of nitric oxide in modulating permeability of hamster cheek pouch in response to adenosine, 5′-diphosphate and bradykinin (1992) Inflammation, 16, p. 295Moncada, The L-arginine: nitric oxide pathway (1992) Acta Physiol. Scand., 145, p. 201Moore, Al-Swayeh, Chong, Evans, Gibson, L-NG-Nitro arginine (L-NOARG), a novel L-arginine-reversible inhibitor of endothelium-dependent vasodilation in vitro (1989) Br. J. Pharmacol., 99, p. 408Mulsch, Busse, NG-Nitro-L-arginine (N5-[imino (nitroamino) methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitrix oxide synthesis from L-arginine (1990) Naunyn-Schmied. Arch. Pharmacol., 340, p. 767Myers, Minos, Jr., Guerra, Jr., Bates, Harrison, Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide (1990) Nature, 345, p. 161Palmer, Ferrige, Moncada, Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor (1987) Nature, 327, p. 524Palmer, Rees, Ashton, Moncada, L-Arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation (1988) Biochem. Byophys. Res. Commun., 153, p. 1251Palmer, Ashton, Moncada, Vascular endothelial cells synthesize nitric oxide from L-arginine (1988) Nature, 333, p. 664Paton, Compound 48/80: a potent histamine liberator (1951) Br. J. Pharmacol., 6, p. 499Ranadive, Ruben, Mechanism of histamine release from rat mast cells by compound 48/80. Comparison with the release induced by cationic protein (1973) Int. Arch. Allergy Appl. Immunol., 44, p. 745Salvemini, Masini, Pistelli, Mannaioni, Vane, Nitric oxide: a regulatory mediator of mast cell reactivity (1991) J. Cardiovasc. Pharmacol., 17, p. S258Shen, Grundemar, Zukowska-Grojec, Hakanson, Wahlestedt, C-terminal neuropeptide Y fragments are mast cell-dependent vasodepressor agents (1991) Eur. J. Pharmacol., 204, p. 249Shore, Burkhalter, Cohen, Jr., A method for the fluorometric assay of histamine in tissues (1959) J. Pharmacol. Exp. Ther., 127, p. 182Spector, Willoughby, The demonstration of the role of mediators in turpentine pleurisy in rats by experimental suppression of the inflammatory changes (1959) The Journal of Pathology and Bacteriology, 77, p. 1Tottrup, Svane, Forman, Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter (1991) Am. J. Physiol., 260, p. G385