Dissociation between the effects of zymosan on the systemic and pulmonary vessels of the rat

Abstract

1 Zymosan, an activator of the alternative complement pathway, (2 to 16mgkg-1) injected intravenously via the tail vein of anaesthetized rats, dose-dependently increased the vascular permeability of lung parenchyma, as measured by the accumulation of 1251-labelled albumin in lungs. 2 Pretreatment of the animals with cyclo-oxygenase inhibitors, indomethacin or ketoprofen (3 mg kg 1) or with the lipoxygenase and cyclo-oxygenase inhibitor, BW755C (40mgkg-') abolished the vascular permeability changes induced by zymosan (16mg kg-1). Neither, the PAF antagonist, WEB 2086 (10mg kg-1) nor the antagonists of mast cell amines, mepyramine and methysergide (3mg kg-) affected the plasma exudation in lungs. Zymosan did not induce any accumulation of labelled albumin in lungs of rats made leucopenic by rabbit anti-neutrophil serum. 3 Zymosan (16mgkg-1) increased the haematocrit. This increase was not modified by indomethacin but reduced by WEB 2086. 3 Intravenous injection of zymosan (3 and 8 mgkg ')in anaesthetized rats transiently increased right ventricular blood pressure and pulmonary arterial pressure, accelerated respiratory rate and decreased systemic blood pressure. 5 WEB 2086 largely reduced the systemic hypotension but did not affect the increase of pulmonary vascular resistance. Indomethacin inhibited the increase of blood pressure in the right ventricle and the modification of the respiratory rate. This drug did not inhibit but increased the systemic hypotension induced by zymosan. 6 Zymosan (16mg kg-) reduced serum complement haemolytic activity by 46%. 7 These data suggest that the pulmonary vascular changes induced by intravascular complement activation with zymosan in rats are mediated by neutrophils and prostanoids while the systemic vascular effects depend mainly on PAF.

Kupffer cell activation in normal and fibrotic livers increases portal pressure via thromboxane A2

“…Firstly, we could demonstrate that intra-portal infusion of b-glucan-rich cell wall particles from S. cerevisiae (zymosan) increases portal pressure in vivo. This portal and therefore also systemic zymosan infusion resulted in a significant decrease of mean arterial pressure as observed earlier [21]. This could be explained by a massive activation of all macrophages and granulocytes in the body comparable to a septic shock.…”

Rodent models of complement activation-related pseudoallergy: Inducers, symptoms, inhibitors and reaction mechanisms

“…It is a glucan with repeating glucose units connected by β-1,3-glycosidic linkages, which activates nuclear factor-κB (NF-κB) signaling in resident macrophages via Toll-like receptors (15). Damas et al performed a series of studies to explore the hemodynamic, pulmonary and hematologic effects of zymosan in rats, and reported the following changes (16)(17)(18)(19)(20)(21). Intravenous treatment with zymosan reduced serum C hemolytic activity and caused leukopenia, thrombocytopenia, as well as decreased blood pressure and increased hematocrit as a result of extravasation of extracellular fluid in various vascular beds (16)(17)(18)(19)(20)(21).…”

“…Damas et al performed a series of studies to explore the hemodynamic, pulmonary and hematologic effects of zymosan in rats, and reported the following changes (16)(17)(18)(19)(20)(21). Intravenous treatment with zymosan reduced serum C hemolytic activity and caused leukopenia, thrombocytopenia, as well as decreased blood pressure and increased hematocrit as a result of extravasation of extracellular fluid in various vascular beds (16)(17)(18)(19)(20)(21). Most importantly, zymosan increased right ventricular systolic pressure and respiratory rate (18), which is also a key finding in pigs after liposome administration (22).…”

“…Intravenous treatment with zymosan reduced serum C hemolytic activity and caused leukopenia, thrombocytopenia, as well as decreased blood pressure and increased hematocrit as a result of extravasation of extracellular fluid in various vascular beds (16)(17)(18)(19)(20)(21). Most importantly, zymosan increased right ventricular systolic pressure and respiratory rate (18), which is also a key finding in pigs after liposome administration (22). WEB 2086, a PAF antagonist, prevented the decreases in blood pressure and right ventricular systolic pressure, while indomethacin decreased the tachypnea and pulmonary hypertension but enhanced the drop in blood pressure and right ventricular systolic pressure.…”

The Hypertensive Effect of Amphotericin B-Containing Liposomes (Abelcet) in Mice: Dissecting the Roles of C3a and C5a Anaphylatoxins, Macrophages and Thromboxane

“…TXB2 is a stable metabolite of TXA2, a strong vasoconstrictor [ 10 ]. Indomethacin, a COX-1 inhibitor abolished the hypertensive effect of recombinant human C3a in anesthetized rats [ 6 ], and attenuated the zymosan-induced increase in right ventricular systolic pressure and exaggerated hypotension, which are characteristic symptoms of CARPA in rats [ 11 ].…”