Effect of leukotriene D₄ on nasal mucosal blood flow, nasal airway resistance and nasal secretion in humans

Abstract

Summary The possible role of leukotriene D4(LTD4)in nasal allergy was investigated in healthy volunteers. Nasal blood flow, nasal airway resistance, nasal discharge and nasal itching and sneezing were examined. LTD4 was found to induce a dose‐response related increase in nasal mucosal blood flow as measured by laser‐Doppler flowmetry. Histamine exhibited similar effects on blood flow in the same concentration range. Nasal airway resistance as recorded by rhinomanometry, increased in a dose‐related manner after topical LTD4. Nasal secretion was obtained by nasal lavage and estimated from a dilution principle. Topical LTD4 did not increase the amount of nasal secretion, whereas a dose‐related increase was found after topical histamine. LTD4 did not cause itching, sneezing or other irritative symptoms. In conclusion, LTD4 may play a role in nasal allergy by increasing blood flow and nasal airway resistance. Itching, sneezing and discharge, however, are apparently not caused by LTD4 but can be accounted for by the release of histamine or other mediators.

Oxymetazoline Inhibits Proinflammatory Reactions: Effect on Arachidonic Acid-Derived Metabolites

“…Particularly leukotrienes such as LTB 4 and leukotriene C 4 , which rise in the nasal fluid of rhinitis patients, are generated and released by virus-infected cells of the respiratory tract (Ananaba and Anderson, 1991;van Schaik et al, 1999;Gentile and Skoner, 2001;Gentile et al, 2003). Leukotrienes such as LTD 4 applied directly to the nasal mucosa of noninfected individuals reproduced symptoms of nasal congestion and rhinorrhea (Bisgaard et al, 1986). Treatments with 5-LO enzyme inhibitors or cysteinyl leukotriene receptor antagonists have been shown to induce a significant clinical benefit because these compounds reduces nasal congestion in allergic rhinitis (Naclerio et al, 1991;Liu et al, 1998;Meltzer et al, 2000).…”

Quality of life in patients with persistent allergic rhinitis treated with desloratadine monotherapy or desloratadine plus montelucast combination

“…Nasal insufflation studies show that both leukotriene C4 (LTC4) and leukotriene D4 (LTD4) induce an increase in nasal mucosal blood flow and nasal airway resistance. [19][20][21] Montelukast is an orally active, highly selective cysteinyl leukotriene type-1 receptor antagonist of leukotreine D4, with affinities approximately two-fold greater than the natural ligand. It is rapidly absorbed, achieving peak plasma concentration (Cmax) in three to four hours and with a mean bioavailability of 64% following a 10 mg oral administration.…”

Vernal keratoconjunctivitis

“…16 Their activities include smooth-muscle contraction, small vessel dilatation, increase in blood vessel permeability, promotion of glycoprotein secretion from epithelial glands, and increase of nasal blood flow and airway resistance. [32][33][34][35][36] It has been demonstrated that leukotrienes are also produced in the conjunctiva 37 and are detectable in tear fluids of patients affected by allergic conjunctivitis including VKC. [38][39][40] Indeed LT concentration in tears increases in allergic subjects following allergen challenge.…”