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 distributed in the mammalian respiratory tract. To examine the responses of human upper airways to ET-1, we investigated the effects of intranasal administration of ET-1 to nine symptomatic allergic and nine nonallergic volunteers. Paper discs were used to administer ET-1 or diluent to one side of the nasal mucosa, and to collect secretions from the ipsilateral (challenged) and contralateral (opposite) nostrils. ET-1 (0.3-10 μg), but not diluent, induced dose-dependent bilateral increases in secretion weights, lysozyme secretion, symptoms of rhinorrhea and itch, and sneezing in both populations. ET-1 did not induce albumin secretion, histamine release, or symptoms of nasal congestion. Compared with the nonallergic subjects, allergic individuals sneezed more and had significantly higher bilateral secretion weights, contralateral lysozyme secretion, and symptoms of rhinorrhea following ET-1 provocation. In summary, ET-1 induced symptoms relevant to inflammatory upper airway diseases in allergic and nonallergic subjects. However, responses of allergic subjects were more pronounced, particularly with respect to symptoms associated with neural reflex responses, such as sneezing and contralateral secretion. Therefore, allergic inflammation enhances responsiveness of the nasal mucosa to ET-1.