Endogenous nitric oxide modifies antigen-induced microvascular leakage in sensitized guinea pig airways

Motohiko Miura, Masakazu Ichinose, Natsuko Kageyama, Masafumi Tomaki, Tsuneyuki Takahashi, Jun Ishikawa, Yuzuru Ohuchi, Tatsuya Oyake, Naomi Endoh, Kunio Shirato

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

To examine the role of endogenous nitric oxide in allergic airway inflammation, we investigated the effect of a nitric oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), on antigen-induced airway microvascular leakage in actively sensitized guinea pigs by using Evans blue dye. Three weeks after sensitization with ovalbumin (10 μg), the tracheas were cannulated, and lungs were artificially ventilated. Animals were pretreated with atropine and propranolol (both 1 mg/kg, intravenously) to avoid neural modification. Ovalbumin inhalation (3 mg/ml, 1 minute) challenge caused significant microvascular leakage in all airway portions, which was significantly suppressed in a dose-dependent manner by pretreatment with intravenous injection of L-NAME (1 and 10 mg/kg) but not with the inactive enantiomer D-NAME (10 mg/kg). This inhibition by L-NAME was significantly reversed by co-administration of L-arginine (100 mg/kg, intravenously). Pretreatment with a vasoconstrictor, phenylephrine (20 μg/kg, intravenously), had no inhibitory effects on antigen-induced airway microvascular leakage despite increasing systemic blood pressure. Inhalation of representative mast cell-derived mediators, histamine (2 mg/ml, 1 minute) or leukotriene D4 (5 μg/ml, 1 minute), produced significant microvascular leakage in all airways. L-NAME (10 mg/kg, intravenously) partially but significantly inhibited leukotriene D4-induced leakage, whereas histamine-induced leakage was not affected. These results suggest that endogenous nitric oxide acts to increase airway microvascular leakage after airway allergic reaction.

Original languageEnglish
Pages (from-to)144-151
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume98
Issue number1
DOIs
Publication statusPublished - 1996

Keywords

  • L-NAME
  • L-arginine
  • histamine
  • leukotriene D
  • mast cell degranulation
  • ovalbumin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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