Studies of Mucociliary Activity and Blood Flow in the Upper Airways, with Special Reference to Endothelins and Nitric Oxide

The aim with this thesis was to investigate effects of vasoactive mediators on mucociliary activity and blood flow in rabbit and human experimental models. Mucociliary activity in vivo and ciliary beat frequency (CBF) in vitro were measured with photoelectric techniques. Blood flow was measured with laser Doppler flowmetry. Substance P (SP) and methacholine increased human nasal blood flow. Pretreatment with ipratropium bromide or lidocaine abolished the blood flow increase induced by methacholine, indicating the involvement of neurogenic mechanisms. The effect of SP was unaffected by lidocaine pretreatment. Endothelins (ET)-1, -2 and -3 were ciliostimulators in vivo and in vitro, their effect being greater in sinus than in tracheal samples. Pretreatment with diclofenac inhibited the ciliostimulation induced by the endothelins, indicating the involvement of the cyclooxygenase pathway. All endothelins decreased mucosal blood flow in the maxillary sinus of the rabbit, ET-3 having the weakest effect. ET-1 decreased blood flow in the human nose. Positive immunostaining for nitric oxide synthase (NOS) was found in the sinus mucosa and sphenopalatine ganglion of the rabbit. The NO substrate L-arginine increased CBF, an increase reversibly blocked by pretreatment with the NOS inhibitor NG-nitro-L-arginine. D-arginine was without effect. The NO donor sodium nitroprusside (SNP) increased mucociliary activity in the rabbit maxillary sinus. This increase was not reduced by pretreatment with atropine, diclofenac, or propranolol. Nebulized SNP increased the NO concentration in nasal air, nasal blood flow, and nasal mucociliary activity in humans, supporting the view that NO is a regulator of mucociliary activity.