Am. J. Respir. Crit. Care Med., Volume 160, Number 2, August 1999, 655-662

Hypertonic Saline Nasal Provocation Stimulates Nociceptive Nerves, Substance P Release, and Glandular Mucous Exocytosis in Normal Humans

JAMES N. BARANIUK, MUSHTAQ ALI, ATSUSHI YUTA, SHEEN-YIE FANG, and KRISTINA NARANCH

Division of Rheumatology, Immunology and Allergy, Georgetown University, Washington, DC; Department of Otorhinolaryngology, Mie University, Mie, Japan; and Department of Otolaryngology, National Cheng Kung University, Tainan, Taiwan, R.O.C.

Hypertonic saline (HTS) induces bronchoconstriction. Potential mechanisms were evaluated in a human nasal provocation model. Aliquots of normal saline (1 × NS, 100 µl) and higher concentrations (3 × NS, 6 × NS, 12 × NS, 24 × NS) were sprayed into one nostril at 5-min intervals. Lavage fluids were collected from the ipsilateral and contralateral sides to determine the concentrations of specific mucus constituents. Nasal cavity air-space volume was assessed by acoustic rhinometry (AcRh). The distribution of substance-P-preferring neurokinin-1 (NK-1) receptor mRNA was assessed by in situ reverse transcriptase-polymerase chain reaction. Unilateral HTS induced unilateral dose-dependent increases in sensations of pain, blockage, and rhinorrhea, the weights of recovered lavage fluids, and concentrations of total protein, lactoferrin, mucoglycoprotein markers, and substance P. Contralateral, reflex-mediated effects were minor. There were no changes in IgG or AcRh measurements. NK-1 receptor mRNA was localized to submucosal glands. HTS caused pain with unilateral substance P release. The presumed nociceptive nerve efferent axon response led to glandular exocytosis, presumably through actions on submucosal gland NK-1 receptors. Vascular processes, including plasma exudation, filling of venous sinusoids, and mucosal edema were not induced in these normal subjects.

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