Chronic passive cigarette smoke exposure augments bronchopulmonary C-fibre inputs to nucleus tractus solitarii neurones and reflex output in young guinea-pigs.

Environmental tobacco smoke (passive smoke), the product of the smoldering end of cigarettes mixed with exhaled mainstream smoke, harms the respiratory health of children. Children living in homes where they are exposed to passive smoke have more coughs (Dodge, 1982; Ekwo et al. 1983), wheeze (Dodge, 1982) and airway obstruction (Wang et al. 1994), increased airway reactivity (Ekwo et al. 1983; Frischer et al. 1992) and more sputum production (Dodge, 1982). In addition, these children have an increased risk of lower respiratory tract illnesses (Strachan & Cook, 1997), an increased rate and earlier onset of asthma (Weitzman et al. 1990), and an increased incidence of sudden infant death syndrome (Klonoff-Coher et al. 1996). Some of the same respiratory symptoms associated with environmental tobacco smoke exposure are also elicited by stimulation of the vagal sensory bronchopulmonary C-fibres. In this regard, studies using direct measures of bronchopulmonary C-fibre impulse activity or indirect measures such as preventing the reflex responses by blocking C-fibre conduction or measuring the local release of tachykinins, indicate that the bronchopulmonary C-fibres are stimulated by acute exposures to components of environmental tobacco smoke including nicotine receptor agonists (Saria et al. 1988), acrolein (Lee et al. 1992) and oxidants (Coleridge et al. 1993), as well as by acute exposures to mainstream tobacco smoke (Lee et al. 1989, 1990; Delay-Goyet & Lundberg, 1991; Pisarri et al. 1991). The stimulated C-fibres initiate both a central and a local reflex (Coleridge & Coleridge, 1984; Saria et al. 1988). The central reflex responses, thought to protect the lung from further injury from inhaled agents, include rapid shallow breathing, expiratory apnoea, cough, bronchoconstriction, increased mucous secretion, hypotension and bradycardia (Coleridge & Coleridge, 1984). The reflex respiratory responses of cough, bronchoconstriction and increased mucous secretion are also hallmark symptoms of chronic environmental tobacco smoke exposure (Dodge, 1982; Ekwo et al. 1983; Frischer et al. 1992; Wang et al. 1994). These observations have led to the suggestion that hyperresponsiveness of the bronchopulmonary C-fibre reflex causes some of the respiratory symptoms evoked or exacerbated by environmental tobacco smoke exposure. Recently, electrophysiological recordings of single bronchopulmonary C-fibre afferent activity in young guinea-pigs have provided more direct evidence for this proposal by showing that chronic exposure to environmental tobacco smoke sensitizes bronchopulmonary C-fibres to both chemical and mechanical stimuli (Mutoh et al. 1999). A number of other studies have also documented an increased excitability of primary lung sensory fibres or sensory fibre somata in the nodose ganglia following exposure to environmental pollutants, including allergen (Undem et al. 1993, 1999; Fischer et al. 1996), sidestream tobacco smoke (Bonham et al. 1996) and ozone (Ho & Lee, 1998; Joad et al. 1998). To our knowledge, however, there are no data on whether the sensitization of primary lung sensory afferent fibres by chronic exposure to an environmental pollutant is sustained in the central circuitry of the reflex or has any physiological consequences on the reflex control of respiratory function. The nucleus tractus solitarii (NTS) is the first site in the central circuitry where afferent signals from the primary bronchopulmonary C-fibres are transmitted and susceptible to modulation. The principal neurotransmitter and a number of neuromodulators at these synapses have been identified (Seifert & Trippenbach, 1995; Sevoz et al. 1996; Wilson et al. 1996; Wang et al. 1997). Signal conditioning at these first central synapses may be pivotal, in that the sensory information may be unfailingly transmitted or further modulated, e.g. amplified, blunted or extinguished. We hypothesized that if an increased responsiveness of the bronchopulmonary C-fibres contributes to the exaggerated respiratory symptoms associated with environmental tobacco smoke via the central reflex pathway, then the increase should be manifest at NTS neurones in the central network and ultimately lead to an increase in at least some component of the reflex output. If, on the other hand, the increased excitability of the sensory fibres is extinguished by signal modulation in the central circuitry, the reflex output may be unchanged. Thus, the purpose of this study was to examine the effects of 5 weeks of exposure to sidestream smoke (the surrogate for environmental tobacco smoke) in young guinea-pigs during the age-equivalent period to human childhood on (1) the baseline and evoked increases in impulse activity of bronchopulmonary C-fibre-activated NTS neurones and (2) the associated reflex changes in phrenic nerve discharge and tracheal pressure measured in the whole animal. As a secondary objective, we also examined the exposure effects on baseline and evoked changes in arterial blood pressure and heart rate. We used the potent C-fibre stimulant capsaicin (Coleridge & Coleridge, 1984).