Pharmacological analysis of the vascular permeability response in the anaphylactic phase of allergic inflammation in rats.
Allergic inflammation was induced by injecting an antigen (azobenzenearsonate-conjugated acetyl bovine serum albumin) solution into a preformed air pouch in the dorsum of sensitized rats. There was a marked increase of vascular permeability during the first 30 min, i.e. the anaphylactic phase, after the antigenic challenge injection. In an attempt to define the mediators responsible for the vascular permeability increase, series of experiments were performed with the aid of various pharmacologic agents. The combined treatment with pyrilamine and methysergide almost completely suppressed the anaphylactic vascular permeability response. However, FPL 55712, a specific antagonist to leukotrienes C4 and D4, components of slow-reacting substance, exerted no effect at doses sufficient to suppress the leukotriene C4-or leukotriene D4-induced vascular permeability increase. Indomethacin treatment was also ineffective. These results suggest that the anaphylactic increase in vascular permeability was mediated primarily by histamine and serotonin, while slow-reacting substance or prostaglandins did not play any significant role. A potent anti-inflammatory steroid, dexamethasone, exerted a dose-dependent inhibitory effect on the anaphylactic increase in vascular permeability without interfering with the liberation of histamine from mast cells. The mechanism of the steroid action is discussed.
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology
D002867:Chromones; D011453:Prostaglandins; D013189:SRS-A; D012701:Serotonin; D003907:Dexamethasone; D006632:Histamine; C006312:FPL 55712; D011738:Pyrilamine; D007213:Indomethacin; D008784:Methysergide