EFFECTS OF INTRANASAL ADMINISTRATION OF ENDOTHELIN-1 TO ALLERGIC AND NONALLERGIC INDIVIDUALS

Endothelin-1 (ET-1), a 21 amino acid peptide, and its receptors are di stributed in the mammalian respiratory tract. To examine the responses of human upper airways to ET-1, we investigated the effects of intran asal administration of ET-1 to nine symptomatic allergic and nine nona llergic volunteers. Paper discs were used to administer ET-1 or diluen t to one side of the nasal mucosa, and to collect secretions from the ipsilateral (challenged) and contralateral (opposite) nostrils. ET-1 ( 0.3-10 mu g), but not diluent, induced dose-dependent bilateral increa ses in secretion weights, lysozyme secretion, symptoms of rhinorrhea a nd itch, and sneezing in both populations. ET-1 did not induce albumin secretion, histamine release, or symptoms of nasal congestion. Compar ed with the nonallergic subjects, allergic individuals sneezed more an d had significantly higher bilateral secretion weights, contralateral lysozyme secretion, and symptoms of rhinorrhea following ET-1 provocat ion. In summary, ET-1 induced symptoms relevant to inflammatory upper airway diseases in allergic and nonallergic subjects. However, respons es of allergic subjects were more pronounced, particularly with respec t to symptoms associated with neural reflex responses, such as sneezin g and contralateral secretion. Therefore, allergic inflammation enhanc es responsiveness of the nasal mucosa to ET-1.