Premium
Dissociation between the effects of zymosan on the systemic and pulmonary vessels of the rat
Author(s) -
Damas Jacques,
Lagneaux Denise
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12468.x
Subject(s) - zymosan , methysergide , prostacyclin , pharmacology , endocrinology , medicine , albumin , lung , blood pressure , chemistry , properdin , respiratory system , vascular permeability , immunology , complement system , antagonist , biochemistry , receptor , antibody , in vitro
1 Zymosan, an activator of the alternative complement pathway, (2 to 16 mg kg −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 125 I‐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 (40 mg kg −1 ) abolished the vascular permeability changes induced by zymosan (16 mg kg −1 ). Neither, the PAF antagonist, WEB 2086 (10 mg kg −1 ) nor the antagonists of mast cell amines, mepyramine and methysergide (3 mg kg −1 ) 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 (16 mg kg −1 ) increased the haematocrit. This increase was not modified by indomethacin but reduced by WEB 2086. 3 Intravenous injection of zymosan (3 and 8 mg kg −1 ) 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 (16 mg kg −1 ) 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.