SUMMARY1. Lung irritant receptors have been studied in rabbits by recording action potentials from single vagal nerve fibres. Some of the rabbits were bilaterally vagotomized, and some paralysed and artificially ventilated.2. The receptors gave rapidly adapting irregular discharges on inflation and deflation of the lungs. Many were stimulated by insufflation of ammonia vapour into the lungs, and some by passage of a fine catheter into the right bronchial tree. The fibres had conduction velocities in the range 3*6-25-8 m/sec.3. The receptors were strongly stimulated by intravenous injections of histamine acid phosphate, 25-100 ,ug/kg. The response was considerably reduced by previous injection of isoprenaline which also reduced the bronchoconstriction due to histamine.4. The receptors were stimulated by intravenous injections of isoprenaline, phenyl diguanide and micro-emboli, and by anaphylaxis induced in rabbits previously sensitized to egg albumin.5. The receptor responses could not be closely correlated in size with simultaneous changes in total lung resistance, lung compliance, tidal volume or breathing frequency.6. It is concluded that, in rabbits with intact vagus nerves, lung irritant receptors contribute to the reflex hyperpnoea and bronchoconstriction of the conditions studied.

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SUMMARY1. The activity of lung irritant receptors during pneumothorax, hyperpnoea and pulmonary congestion has been studied by recording from single vagal nerve fibres from the receptors in rabbits.2. The receptors were stimulated during induction and during removal of pneumothorax.3. Pneumothorax caused a greater depression of minute volume in bilaterally vagotomized rabbits, compared with those with intact vagus nerves.4. Hyperpnoea due to breathing through an added dead space increased the discharge of the receptors. Experiments on paralysed and artificially ventilated rabbits showed that this was not a direct action of the asphyxial changes in blood gas tensions.5. Pulmonary congestion, induced by inflating a balloon in the left atrium, stimulated the receptors in paralysed artificially ventilated rabbits.6. The evidence that the receptors cause vagal reflex hyperpnoea and bronchoconstriction is discussed, together with their role in the reflex ventilatory and bronchomotor changes in the conditions studied.

Lung irritant receptors in anaesthetized rabbits are stimulated by deflations and large inflations of the lungs, with irregular and rather rapidly adapting discharges. After deflation the spontaneous discharge of the receptors is increased, and dynamic compliance is decreased. After inflation the spontaneous discharge is decreased, and compliance is increased. The responses of the receptors to inflation and deflation and the relationship with compliance suggest that they are part of the vagal reflex mechanism stimulating breathing or inspiratory activity in these conditions. Deflation of the lungs, whether by negative pressure applied to the trachea, by compression of the chest or by pneumothorax, stimulates breathing primarily by a vagal reflex often with hyperventilation (a fall in systemic arterial pCO2) (see Discussion for references). This vagal reflex hyperpnoea could be due to a decrease in tonic activity in pulmonary stretch (inflation) receptors, since these receptors inhibit breathing [e.g. Adrian, 1933;Paintal, 1963;Widdicombe, 1964] and a decrease in inhibition would cause respiratory stimulation. However, several studies have indicated that deflation stimulates breathing by a vagal pathway other than that from pulmonary stretch receptors (see Discussion).Recent studies of activity in afferent fibres from 'lung irritant receptors' in rabbits show that they are stimulated by deflation of the lungs produced either by negative pressure applied to the tracheal cannula or by pneumothorax [Homberger, 1968;Mills, Sellick and Widdicombe, 1969a;Sellick and Widdicombe, 1969]. The receptors probably lie between the epithelial cells of the bronchi and bronchioles. Since these receptors are thought to stimulate breathing they could contribute to the Hering-Breuer deflation reflex.The lung irritant receptors also respond to large inflations of the lungs, which can elicit a vagally-mediated 'gasp' or inspiratory-augmenting reflex [Knowlton and Larrabee, 1964; Cross, 1961;Godfrey, 1968;Widdicombe, 1967]. This reflex is enhanced by collapse of the lungs (decreased compliance) [Reynolds, 1962;Reynolds and Hilgeson, 1965].The present paper describes experiments designed to see whether the properties of lung irritant receptors are consistent with their playing a role in the inspiratory-augmenting vagal reflex responses to lung deflations and inflations. Some of the results have been published in abstract [Mills et al., 1969b]. METHODSRabbits were anaesthetized with sodium pentobarbitone (Nembutal, Abbott), approximately 50 mg/kg, intravenously. The animals were supine. A tracheal cannula 153

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