Histamine receptors that influence blockage of the normal human nasal airway.

1. The aim of this study was to investigate the mechanisms by which histamine causes nasal blockage. Histamine, 40-800 microg, intranasally into each nostril, induced significant blockage of the nasal airway in normal human subjects, as measured by acoustic rhinometry. 2. Oral pretreatment with cetirizine, 5-30 mg, the H1 antagonist, failed to reverse completely the nasal blockage induced by histamine, 400 microg. 3. Dimaprit, 50-200 microg, the H2 agonist, intranasally, caused nasal blockage, which was reversed by oral pretreatment with ranitidine, 75 mg, the H2 antagonist. 4. A combination of cetirizine, 20 mg, and ranitidine, 75 mg, caused greater inhibition of the nasal blockage caused by histamine, 400 microg, than cetirizine alone. In the presence of both antagonists, there was residual histamine-induced nasal blockage. 5. R-alpha-methylhistamine (R-alpha-MeH), 100-600 microg, the H3 agonist, intranasally, caused nasal blockage, which was not inhibited by either cetirizine or ranitidine. 6. Thioperamide, 700 microg, the H3 antagonist, intranasally, reversed the R-alpha-MeH-induced nasal blockage. Thioperamide alone had no significant action on the nasal blockage induced by histamine, 400 and 1000 microg, but, in the presence of cetirizine, 20 mg, thioperamide further reduced the histamine-induced nasal blockage. 7. Corynanthine, 2 mg, the alpha1-adrenoceptor antagonist, administered intranasally, caused nasal blockage. 8. Corynanthine produced a greater increase in nasal blockage when in combination with bradykinin compared to its combination with R-alpha-MeH. 9. There appears to be a contribution of H1, H2 and H3 receptors to histamine-induced nasal blockage in normal human subjects. The sympathetic nervous system actively maintains nasal patency and we suggest that activation of nasal H3 receptors may downregulate sympathetic activity.