Effect of respiratory tract viral infection on murine airway β‐adrenoceptor function, distribution and density

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Abstract
1 The effects of a respiratory tract viral infection on β-adrenoceptor density, distribution and function were investigated in murine airways. 2 Following intranasal inoculation of CBA/CaH mice with influenza A/PR-8/34 virus, the virus proliferated rapidly in trachea (peak titres 2 days post-inoculation) and lung (peak titres 4–6 days post-inoculation). Respiratory tract viral infection was associated with a significant increase in lung weight (88% higher than control mice at day 6 post-inoculation) that was related temporally to the development of peripheral lung inflammation and consolidation. 3 Analysis of specific binding of [125I]-cyanopindolol to β-adrenoceptors revealed that on days 2, 4 and 8 post-inoculation with virus, mouse isolated tracheal sections contained, on average, 40% more β-adrenoceptors than tracheal sections from time matched control mice. Subsequent quantitative autoradiographic studies demonstrated that this increase in total tracheal β-adrenoceptors was due primarily to a 90% increase in the density of β-adrenoceptors in the tracheal epithelium in virus-infected mice. 4 In contrast, virus-infection had no significant effect on the density of β-adrenoceptors in tracheal airway smooth muscle, although within 2 days of inoculation with virus, mouse tracheal smooth muscle segments were approximately 2 fold less sensitive to the β-adrenoceptor agonist, noradrenaline (mean pD2 = 6.57 ± 0.04, n = 24) and to the adenylyl cyclase-activator forskolin (mean pD2 = 6.78 ± 0.04, n = 12) compared to segments from control mice (mean pD2 = 6.84 ± 0.06 for noradrenaline; mean pD2 = 7.03 ± 0.07 for forskolin). Similar values were obtained 8 days post-inoculation. At day 2, but not day 8 post-inoculation with virus, relaxation responses to theophylline were also marginally attenuated compared with controls. 5 Mouse isolated tracheal segments obtained 2 days after virus inoculation and segments from time-matched control mice were equisensitive to the spasmogenic actions of the muscarinic cholinoceptor agonist, carbachol. However, tracheal segments from mice inoculated with virus were less responsive to carbachol on day 4 (mean pD2 = 6.45 ± 0.04, n = 8) and day 8 (mean pD2 = 6.45 ± 0.02, n = 12) compared to control preparations (day 4, mean pD2 = 6.73 ± 0.06, n = 8; day 8, mean pD2 = 6.65 ± 0.04, n = 12, P < 0.05). In contrast, endothelin-1-induced contractions of tracheal smooth muscle were not affected by virus-infection. 6 These data demonstrate that respiratory tract viral infection can produce significant tissue-selective changes in airway β-adrenoceptor density as well as small reductions in airway smooth muscle muscarinic cholinoceptor and β-adrenoceptor function.