Endothelial reactivity to the immediate hypersensitivity reaction of guinea pig pulmonary artery.
Ovalbumin at low doses (0.1 microg/ml) caused pronounced relaxations in the precontracted pulmonary arteries of sensitized guinea pigs but, at high doses, (1-100 microg/ml) the relaxations were blunted by the contractions. The relaxations in response to ovalbumin challenge were related to histamine, which is released during the immediate hypersensitivity reaction, because they were almost blocked by mepyramine (10(-5) M) plus cimetidine (10(-4) M) pretreatment and never observed in unsensitized animal arteries. Additionally, the inhibition of relaxations by endothelium removal or N(G)-nitro-L-arginine (L-NOARG, 10(-4) M) treatment implies that the phenomenon requires endothelial nitric oxide synthesis. However, the contractions appear to depend on leukotriene production since they were markedly blocked in the presence of 2(S)-hydroxy-3(R)-[(2-carboxyethyl)thio]-3-[2-(8-phenyloctyl)pheny l]- propanoic acid (SKF 104353, 10(-5) M), a leukotriene receptor antagonist. These results indicate that ovalbumin-induced nitric oxide and histamine H(2) receptor dependent relaxations in pulmonary artery may have an important role in the recovery of the increased pulmonary vascular resistance during the hypersensitivity reaction.
Akar
F
F
Gazi University, Faculty of Pharmacy, Department of Pharmacology, Etiler, 06330, Ankara, Turkey. akarf@tr-net.net.tr
D000818:Animals; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000503:physiopathology*; D066298:In Vitro Techniques; D020024:Leukotriene Antagonists / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011738:Pyrilamine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D003998:Dicarboxylic Acids; D016232:Endothelins; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D020024:Leukotriene Antagonists; D019335:Nitroarginine; D010047:Ovalbumin; D019001:Nitric Oxide Synthase; D011738:Pyrilamine; C052393:pobilukast