Vagal Deflation and Inflation Reflexes Mediated by Lung Irritant Receptors

Abstract

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

Histamine-induced end-tidal inspiratory activity and lung receptors in cats

“…RAR activity increases and SAR activity decreases when Ptr is lowered [19][20][21]. Thus, CNAP-induced ETIA ( fig.…”

“…It is known from the literature [15,[19][20][21] that the activities of SARs and/or RARs are affected when changing the experimental conditions from control to CNAP or CPAP and after administration of histamine. In turn, the activities of these receptors affect the behaviour of the inspiratory off-switch and on-switch mechanisms, and, therefore, also tE, EMGPK and t. This was also reflected by the changes in tE and t that were observed in individual cats when changing from one experimental condition to another (tables 1 and 2).…”

“…It has been shown, in animals, that the activity of RARs increases with decreasing Ptr [11,21], by hyperinflation [11], and by administration (intravascular or inhalation) of histamine [11,12,14,25,26]. Histamine is believed to stimulate RARs both indirectly by a mechanical effect and by a direct chemical effect [12,27].…”

The Control of Breathing in Clinical Practice

“…20 However, animal studies show that they are stimulated by conditions that increase airflow resistance and decrease lung compliance. 21 Thus, their most important function may be to detect pathophysiologic changes in the airways. RARs also seem to be responsible for the augmented breathing and sighs that occur sporadically during normal breathing that helps to prevent atelectases.…”

Demonstrations

“…However, the precise action of the lung irritant receptors on breathing is controversial. Different methods of stimulating irritant receptors have produced widely differing changes in the pattern of breathing (Sellick & Widdicombe, 1970;Widdicombe & Winning, 1976;Dain, Boushey & Gold, 1975) and until now it has been difficult to assign a consistent role to these receptors.…”