Pulmonary afferent fibres of small diameter stimulated by capsaicin and by hyperinflation of the lungs.

Abstract

This paper describes experiments in which impulses have been recorded from afferent vagal fibres whose endings were located in the lung. These fibres differed from the pulmonary stretch fibres described by Adrian (1933) and subsequent workers in that their spontaneous activity was sparse and irregular and showed no respiratory modulation at normal ventilation volumes. The fibres were stimulated, however, by inflating the lungs with larger volumes. The fibres appeared to be of small diameter, having a mean conduction velocity of 16 m/sec and a blocking temperature of 1-6°C.These slowly conducting fibres were identified in the following way. Capsaicin, a decylenic acid amide of vanillylamine, injected intravenously produces bradyeardia, systemic hypotension and apnoea (Toh, Lee & Kiang, 1955; Porsz6asz, Such & Porszasz-Gibiszer, 1957). Porsztasz et al. (1957) suggested that this triad of effects was evoked reflexly by stimulation of baroreceptors in the extrapulmonary parts of the pulmonary artery.Subsequently, Coleridge, Coleridge & Kidd (1964) found that although pulmonary arterial baroreceptors undoubtedly played a part in mediating the reflex effects, some other afferent endings within the vascular bed of the lung itself were probably involved. A search was therefore made for intrapulmonary receptors which were stimulated by capsaicin. The afferent fibres described in the present paper were encountered in the course of this work. They were the only pulmonary fibres consistently stimulated by capsaicin, the drug having little or no effect on the activity of pulmonary stretch fibres of the type described by Adrian (1933). METHODSTwenty-seven dogs (9-32 kg) were anaesthetized with morphine sulphate (15 mg subcutaneously) followed either by chloralose (0-08 g/kg intravenously) or by a 1:1 mixture (0-25 ml./kg intravenously) of Dial Compound (allobarbitone 100 mg/ml., urethane 400 mg/ ml., Ciba) and Nembutal (sodium pentobarbitone 60 mg/ml., Abbott Laboratories) solutions.

Identification of vagal sensory receptors in the rat lung: are there subtypes of slowly adapting receptors?

“…This appears to be the case in dogs as well (Coleridge et al 1965(Coleridge et al , 1968 Coleridge & Coleridge, 1977). C fibre endings demonstrated a dose-dependent response to capsaicin injection.…”

“…Blood pressure decreased dramatically while little or no changes were observed in nerve activity or intratracheal pressure. SENSORY RECEPTORS IN THE RAT LUNG the range reported for C fibres in the cat (Paintal, 1957(Paintal, , 1973 and dog (Coleridge, Coleridge & Luck, 1965;Coleridge & Coleridge, 1977). The base-level activity of C fibres during the ventilation approximating eupnoeic conditions was 90+84 impulses min1 and is similar to that reported for those in the dog (Kappagoda, Mah & Teo, 1987;Jonzon, Pisarri, Roberts, Coleridge & Coleridge, 1988) responded to stepwise and constant-pressure inflations of the lungs, but the response was weak even at high intratracheal pressures (3-4 x tidal volume or 30-40 cmH20).…”

“…The conduction velocity (Coleridge et al 1965;Paintal, 1973;Coleridge & Coleridge, 1977), base-level activity (Kappagoda et al 1987;Jonzon et al 1988) and mechanical sensitivity (Coleridge et al 1965;Armstrong & Luck, 1974;Kappagoda et al 1987) of C fibres of other species compare similarly with C fibre endings in the rat lung. Rat C fibre endings have a high pressure threshold and adaptation characteristics that are not considered rapidly adapting to mechanical stimuli.…”

The reflex effects of alterations in lung volume on systemic vascular resistance in the dog

“…(4) There is a close relation between the volume and pressure used to inflate the lungs and the degree of vasodilatation, suggesting that the pulmonary receptors concerned are probably of the slowly adapting type; and (5) veratridine, an alkaloid known to stimulate pulmonary stretch receptors (Meier, Bein & Helmich, 1949;Dawes, Mott & Widdicombe, 1951), caused a reflex reduction in systemic vascular resistance, a diminution in respiratory movements and slowing of the beating atria when injected into the pulmonary circulation. A second type of receptor in the lungs has recently been shown by Coleridge, Coleridge & Luck (1965) to be stimulated by veratridine. Since these receptors show no activity during eupnoeic breathing but are excited by hyperinflation of the lungs, they are unlikely to be responsible for the reflex vasomotor responses observed by us, at least those occurring with inflation volumes which result in the lungs not exceeding their normal function residual capacity.…”

Stimulation of pulmonary C fibres decreases coronary arterial resistance in dogs.

“…The receptors for this reflex are believed to be located close to the pulmonary capillaries (Hung, Hertweck, Hardy & Loosli, 1972, 1973Fox, Bull & Guz, 1980) and, because of this location, have been called 'juxta-pulmonary capillary receptors' or J receptors (Paintal, 1969). The afferent fibres innervating the J receptors travel in the vagus and are called pulmonary C fibres (Coleridge et al 1964;Coleridge, Coleridge & Luck, 1965;Coleridge & Coleridge, 1977 a, b) The J receptors are stimulated if capsaicin is injected into the pulmonary artery or right atrium, but not if capsaicin is injected into the left atrium (Coleridge, Coleridge, Roberts, Kaufman & Baker, 1982). The onset of the chemoreflex in dogs occurs within 4 s of the injection of capsaicin into the right atrium (Dawes & Comroe, 1954;Coleridge et al 1964).…”