Modulation Of Central Histaminergic Neurons On Asthmatic Rats

【Objective】To explore the effect of central histaminergic neurons in the tuberomammillary nucleus(TMN) of posterior hypothalamus on asthma and its possible mechanisms.【Methods】Healthy male SD rats were used in the present experiment and divided into each group randomly. Rats were sensitized with ovalbumin(OA) solution injected intraperitoneally and challenged with OA aerosol inhalation to prepare asthma models. In asthmatic rats challenged by OA solution injected intravenously, the electrical activities of TMN in posterior hypothalamus were recorded with MD2000 biological signal collecting system and the power spectra were analysed. TMN was lesioned or stimulated electrically, or histamine H3 receptor agonist R-(α)-methylhistamine (RMHA) or antagonist thioperamide (THIO) was microinjected into TMN and the effects on pulmonary functon, including EMGdi frenquency,EMGdi integral,MVV,TE /TI,Raw and Cdyn were investigated, histamine content in rostral ventrolateral medulla (RVLM) were detected with high-performance liquid chromatography (HPLC). Histamine H1 receptor antagonist chlorpheniramine or histamine H2 receptor antagonist cimetidine was microinjected into RVLM, and the pulmonary functon was monitored.【Results】1) Compared with control group, the percentage ofα,β1,β2 wave in the electrical activities of TMN of asthmatic rats increased significantly while the percentage ofδandθwave decreased and the total power increased. 2) Compared with control group, histamine content in RVLM of the asthmatic rats increased remarkably. 3) Compared with the corresponding control group, electric lesion of TMN or histamine H3 receptor antagonist microinjected into TMN increased EMGdi frenquency,TE /TI,Raw and histamine content in RVLM of the asthmatic rats, and decreased EMGdi integral,MVV and Cdyn. 4) Compared with the corresponding control group, electric stimulation of TMN or histamine H3 receptor agonist microinjected into TMN decreased EMGdi frenquency,TE /TI,Raw and histamine content in RVLM of the asthmatic rats, and increased EMGdi integral,MVV and Cdyn. 5) Compared with the corresponding control group, histamine H1 receptor antagonist chlorpheniramine microinjected into RVLM decreased EMGdi frenquency,TE /TI,Raw and histamine content in RVLM of the asthmatic rats, and increased EMGdi integral,MVV and Cdyn, while histamine H2 receptor antagonist cimetidine microinjected into RVLM produced no significant changes in pulmonary function.【Conclusion】1) Central histaminergic neurons in Tuberomammillary nucleus of posterior hypothalamus are activated in asthmatic rats. 2) Central histamine may play an important role in asthma and probably the histamine H1 receptor in RVLM is involved.