Effects of Substance P and Methacholine on Mucosal Blood Flow in the Upper Airways

Abstract

The aims of the present investigation were to examine the in vivo effects of substance P (SP) and methacholine on blood flow measured by laser Doppler technique in the maxillary sinus of the rabbit and in the human nasal mucosa. In the rabbit, the test substances were administered by intra-arterial catheter, and the laser Doppler probe was inserted into the maxillary sinus through a trepanation in the anterior wall. In the human nose, the laser Doppler probe was directed toward the nasal septum at the level of the anterior margin of the middle turbinate, and the test substances were administered as aerosols into the ipsilateral nostril. In the rabbit maxillary sinus, both SP and methacholine increased the blood flow, the maximum increases obtained being 13.5 ± 3.1% and 39.0 ± 5.6% after challenges with SP at 0.1 μg/kg and methacholine at 0.5 μg/kg, respectively. The rabbits displayed a decrease in blood flow after challenges at higher dosages of both SP and methacholine, accompanied by a simultaneous fall in systemic blood pressure. Atropine given IV five minutes before methacholine abolished the effects of this compound in the rabbit. The blood flow in the human nose was unaffected by saline controls, whereas it was increased both by SP and by methacholine, the increases being 34.9 ± 6.0% after challenges with SP 1.0 nmol and 119.2 ± 15.1% after challenges with methacholine 5.0 μmol. According to acoustic rhinometry, neither SP nor methacholine had, at the doses used, any effect on human nasal patency. Pretreatment with lidocaine hydrochloride spray into the human nose did not affect the increase in nasal blood flow induced by SP, but abolished the methacholine-evoked blood flow increase. Pretreatment with ipratropium bromide spray into the human nose abolished the increase in blood flow induced by methacholine. The results of the present study indicate that blood flow in the upper airways of humans and rabbits may increase due to release of SP or acetylcholine in vivo, an event that occurs after exposure to airway irritants. The vasodilation in the human nose produced by acetylcholine may be due to a neurogenic reflex, in contrast to the effect of SP.