Cysteinyl
leukotrienes (CysLTs:
LTC4,
LTD4, and
LTE4) are a family of potent inflammatory mediators that appear to contribute to the pathophysiologic features of
allergic rhinitis. Because treatment with a
CysLT1 receptor antagonist and a
5-lipoxygenase inhibitor modified
allergen-induced
nasal blockage in patients with
allergic rhinitis, and CysLTs were detected in nasal cavity lavage fluid, it has been suggested that CysLTs act as significant inflammatory mediators in
allergic rhinitis. The role of CysLTs was evaluated in our experimental
allergic rhinitis model in sensitized guinea pigs which shows biphasic
nasal blockage,
sneezing and nasal hyperresponsiveness to
LTD4 induced by repetitive inhalation challenge with Japanese cedar pollen. In this model, the
CysLT1 receptor antagonist
pranlukast suppressed the late-phase
nasal blockage but not early blockage and
sneezing. Nasal hyperresponsiveness (
nasal blockage) to
LTD4 was largely blocked by
pranlukast,
naphazoline, and
N omega-nitro-L-arginine-methyl ester. The results demonstrate that
nasal blockage induced by CysLTs is mainly due to dilatation of nasal blood vessels, which can be induced by the
nitric oxide produced through
CysLT1 receptor activation. On the other hand, when pollen inhalation challenge was performed in the presence of nasal hyperresponsiveness,
antigen-induced biphasic
nasal blockage and
sneezing were considerably enhanced and CysLTs contributed to both symptoms, suggesting that nasal hyperresponsiveness induces aggravation of
antigen-induced nasal symptoms. The results presented in this study further suggest that our model is a good representative of human
allergic rhinitis and offer evidence that CysLTs are chemical mediators mainly responsible for allergic nasal symptoms.