Abstract
Histamine induces a variety of responses including contraction of airway smooth muscle, vasodilation, plasma exudation and mucus production in acute allergic reactions and is an important proinflammatory mediator in bronchial asthma. It also reduces tracheal tone centrally, through the sympathetic pathway. This study examined whether central histamine can attenuate airway responsiveness to methacholine (MCh) in asthma. C57BL/ 6 male mice were sensitized and challenged with ovalbumin (OVA) or saline. The enhanced pause (Penh) was determined as an index of airway obstruction 24 h after the last challenge using a barometric whole body plethysmograph. MCh inhalation increased Penh in a dose-dependent manner and was higher in OVA-sensitized and challenged mice (OVA mice) than in control mice. This suggests that OVA mice have airway hyperresponsiveness (AHR) . Eosinophils accumulated around bronchioles and serum total IgE was increased in OVA mice. Therefore, our system can be regarded as a model of asthma in mice. Histamine administered into the lateral ventricle (i.c.v.) of asthmatic mice lowered AHR when compared to control animals given artificial cerebrospinal fluid i.c.v. Down-regulation of AHR in response to histamine i.c.v. was not seen in asthmatic mice after injection of the β 2-adrenoceptor antagonist butoxamine. These results suggest that central histamine attenuates AHR in asthmatic model (AM) mice via β2-adrenaline receptors, and possibly via the sympathetic nervous system.
