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EUROPEAN JOURNAL OF PHARMACOLOGY, vol.395, no.3, pp.225-228, 2000 (SCI-Expanded)
Ovalbumin at low doses (0.1 mu g/ml) caused pronounced relaxations in the precontracted pulmonary arteries of sensitized guinea pigs but, at high doses, (1-100 mu g/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)phenyl]-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. (C) 2000 Elsevier Science B.V. All rights reserved.