Pharmacological characterization of polycation‐induced rat hind‐paw oedema

Abstract

IThe inflammatory response induced by poly-L-arginine in the rat hind-paw was studied both by measuring paw oedema and histologically. 2 The paw volume was measured with a hydroplethysmometer at 0.5, 1, 2, 4, 6 and 18 h after the subplantar injection of the polycation. Protein extravasation was evaluated with Evans' blue and the histology studied by light microscopy. 3 Poly-L-arginine (12, 24, 43 and 115 kD) caused dose-and molecular weight-dependent oedema which had a rapid onset and long duration. Evans' blue extravasation paralleled the oedema induced by poly-Larginine. Microscopic examination of the paws at early stages of oedema formation showed exuberant liquid exudate with no inflammatory cells. After 18 h, a cellular infiltrate was present, consisting mainly of mononuclear cells. 4 Indomethacin, dexamethasone, BW755c or the PAF-antagonist WEB 2086 caused no significant inhibition of the poly-L-arginine-induced oedema. Cyproheptadine had inhibitory effects only on the early stages of the polycation-induced oedema. Similar results were observed with rats depleted of histamine and 5-hydroxytryptamine. 5 Heparin, a polyanion, injected in the rat paw caused a marked inhibition of the polycation-induced oedema. NG-monomethyl-L-arginine (LNMMA), an inhibitor of EDRF synthesis, injected locally also produced a marked inhibition, but this inhibition was reversed by iloprost. 6 These results suggest that the oedema induced by polycations was due to their cationic charge. The inhibitory effect of LNMMA is probably due to a decrease in vascular flow rather than a decrease in vascular permeability.

Nitric Oxide Synthase Inhibitors Have Opposite Effects on Acute Inflammation Depending on Their Route of Administration

“…Given their lack of selectivity, it is conceivable that systemic administration may also inhibit ecNOS remote from the inflammatory locus, resulting in vasoconstriction, reduced blood delivery to the inflamed site, and, thus, a reduction in inflammation. Indeed, it was shown that the anti-inflammatory effects of L-arginine analogues, given systemically, could be reversed by vasodilators (8,9,24). In agreement with these studies, we also found that when NOS inhibitors were injected i.p., immediately before intrapleural injection of carrageenin, pleural exudates were significantly reduced.…”

Diazepam effects on carrageenan-induced inflammatory paw edema in rats: Role of nitric oxide

“…Acute administration of L-NAME reduced albumin extravasation and decreased local microvascular blood flow in rat (Hughes et al, 1990;Ialenti et al, 1993), guinea-pig (Teixeira et al, 1993) and rabbit (Mariani-Pedroso et al, 1995) skin, as well as edema formation in the paw (Antunes et al, 1990(Antunes et al, , 1992Ialenti et al, 1993;Giraldelo et al, 1994). Together, these findings indicate that NO is a key element for some relevant aspects of inflammation being most probably largely responsible for edema.…”

Effect of heparin and a low‐molecular weight heparinoid on PAF‐induced airway responses in neonatally immunized rabbits

“…1986). Heparin has also been shown to inhibit the increased vascular permeability induced by a variety of inflammatory mediators including histamine, bradykinin, prostaglandin El (Carr, 1979) and cationic proteins (Needham et al, 1988;Antunes et al, 1990;Sasaki et al, 1991). Evidence suggests that heparin can inhibit T-lymphocyte activation (Frieri & Metcalfe, 1983), trafficking (Sy et al, 1983;Willenborg & Parish, 1988;Lider et al, 1990) and delayed hypersensitivity responses (Frieri & Metcalfe, 1983;Sy et al, 1983;Lider et al, 1990) via a mechanism unrelated to its anti-coagulant properties.…”