Blood pressure changes alter tracheobronchial cough: computational model of the respiratory-cough network and in vivo experiments in anesthetized cats

Abstract

We tested the hypothesis, motivated in part by a coordinated computational cough network model, that alterations of mean systemic arterial blood pressure (BP) influence the excitability and motor pattern of cough. Model simulations predicted suppression of coughing by stimulation of arterial baroreceptors. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms (EMG) of inspiratory parasternal, expiratory abdominal, laryngeal posterior cricoarytenoid (PCA), and thyroarytenoid muscles along with esophageal pressure (EP) and BP were recorded. Transiently elevated BP significantly reduced cough number, cough-related inspiratory, and expiratory amplitudes of EP, peak parasternal and abdominal EMG, and maximum of PCA EMG during the expulsive phase of cough, and prolonged the cough inspiratory and expiratory phases as well as cough cycle duration compared with control coughs. Latencies from the beginning of stimulation to the onset of cough-related diaphragm and abdominal activities were increased. Increases in BP also elicited bradycardia and isocapnic bradypnea. Reductions in BP increased cough number; elevated inspiratory EP amplitude and parasternal, abdominal, and inspiratory PCA EMG amplitudes; decreased total cough cycle duration; shortened the durations of the cough expiratory phase and cough-related abdominal discharge; and shortened cough latency compared with control coughs. Reduced BP also produced tachycardia, tachypnea, and hypocapnic hyperventilation. These effects of BP on coughing likely originate from interactions between barosensitive and respiratory brainstem neuronal networks, particularly by modulation of respiratory neurons within multiple respiration/cough-related brainstem areas by baroreceptor input.

Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network

“…More generally, decreased activity of t-E neurons during inspiration may operate to counterbalance the suppressive influence of increased arterial blood pressure on inspiratory drive due to excitation and disinhibition of t-E activity (Fig. 8B, 5) via raphé circuits during chemoreceptorand cough-evoked increases in blood pressure (Lindsey et al 1998;Poliaček et al 2011).…”

The cough reflex is upregulated by lisinopril microinjected into the caudal nucleus tractus solitarii of the rabbit

“…For a more exhaustive appraisal and discussion on the spread of injected drugs see also Lipski et al, 1988;Nicholson, 1985;Sykova and Nicholson, 2008. Interestingly, changes in mean arterial blood pressure that may affect the cough reflex (Poliacek et al, 2011) were not observed. The absence of consistent changes in mean arterial blood pressure following microinjections of losartan and lisinopril is in agreement with previous studies on the effects of different types of ACE inhibitors or sartans microinjected into the NTS of normotensive control animals (Arnold et al, 2010;Chitravanshi and Sapru, 2011;Katsunuma et al, 2003;Wang et al, 2007).…”

“…The inspiratory (T I ) and expiratory (T E ) times, as well as the total duration of the respiratory cycle (T T ) were measured on recordings of raw phrenic nerve activity (Mutolo et al, 2014;Poliacek et al, 2011). The respiratory frequency was subsequently calculated (breaths/min).…”

Downregulation of the cough reflex by aclidinium and tiotropium in awake and anesthetized rabbits

“…It was scheduled to ensure the complete development of bronchodilator effects (see Methods). It is noteworthy that changes in the ongoing respiratory activity or in arterial blood pressure, that have been proved to affect the timing and intensity of cough responses [8,24,37], were not induced by the two employed LAMAs.…”

“…The inspiratory (T I ) and expiratory (T E ) times, as well as the total duration of the respiratory cycle (T T ) were measured on recordings of raw phrenic nerve activity [28,37]. The respiratory frequency was subsequently calculated (breaths/min).…”