Heightened respiratory‐parasympathetic coupling to airways in the spontaneously hypertensive rat

Abstract

Key points Carotid body (CB) chemoreceptors are hyperactive in hypertension, and their acute activation produces bronchoconstriction. We show that the respiratory‐modulated bronchiolar tone, pulmonary parasympathetic efferent activity, and the firing frequency and synaptic excitation of bronchoconstrictor motoneurones in the nucleus ambiguus were all enhanced in spontaneous hypertensive (SH) rats. In SH rats, CB denervation reduced the respiratory‐related parasympathetic‐mediated bronchoconstrictor tone to levels seen in normotensive rats. Chemoreflex evoked bronchoconstrictor tone was heightened in SH versus normotensive rats. The intrinsic electrophysiological properties and morphology of bronchoconstrictor motoneurones were similar across rat strains. The heightened respiratory modulation of parasympathetic‐mediated bronchoconstrictor tone to the airways in SH rats is caused by afferent drive from the CBs. Abstract Much research has described heightened sympathetic activity in hypertension and diminished parasympathetic tone, especially to the heart. The carotid body (CB) chemoreceptors exhibit hyperreflexia and are hyperactive, providing excitatory drive to sympathetic networks in hypertension. Given that acute CB activation produces reflex evoked bronchoconstriction via activation of parasympathetic vagal efferents, we hypothesised that the parasympathetic bronchoconstrictor activity is enhanced in spontaneously hypertensive (SH) rats and that this is dependent on CB inputs. In situ preparations of Wistar and SH rats were used in which bronchiolar tone, the pulmonary branch of the vagus (pVN) and phrenic nerves were recorded simultaneously; whole cell patch clamp recordings of bronchoconstrictor vagal motoneurones were also made from the nucleus ambiguus. Bronchiolar tone, pVN and bronchoconstrictor motoneurones were respiratory modulated and this modulation was enhanced in SH rats. These differences were all eliminated after CB denervation. Stimulation of the CBs increased the phrenic frequency that caused a summation of the respiratory‐related increases in pVN, resulting in the development of bronchoconstrictor tone. This tone was exaggerated in SH rats. The enhanced respiratory‐parasympathetic coupling to airways in SH rats was not due to differences in the intrinsic electrophysiological properties of bronchoconstrictor motoneurones but reflected heightened pre‐inspiratory‐ and inspiratory‐related synaptic drive. In summary, in SH rats the phasic respiratory modulation of parasympathetic tone to the airways is elevated and the greater development of this bronchoconstrictor tone is caused by the heightened afferent drive originating from the CBs. Thus, targeting the CBs may prove effective for increasing lower airway patency.

Icariin protects myocardial cells in spontaneously hypertensive rats by inhibiting mitochondrial and endopla smic reticulum stress related pathways

“…The degree of hypertension increases with maturity of the rats, and it reaches peak blood pressure at about 24 weeks. Thus, SHR is an ideal animal model for carrying out research on hypertension-induced heart disease [13,14].…”

Cellular basis of learning and memory in the carotid body

“…Through a number of putative mechanisms this results in modulation of potassium channels in glomus cells causing their depolarisation and release of transmitters that depolarises the terminals of petrosal neurones that send projections into the brainstem. This results in activation of the chemoreflex arc which acts on the ventral respiratory column in the medulla oblongata causing an increase in ventilation ( Koshiya et al, 1993 ); several respiratory neuron types project to the RVLM ( Koshiya and Guyenet, 1994 ) to cause enhanced respiratory modulation of vasomotor sympathetic activity causing blood pressure to rise ( Moraes et al, 2011 ), and to the cardiac and laryngeal projecting parasympathetic pre-ganglionic neurons in the nucleus ambiguus causing bradycardia and bronchoconstriction respectively ( Simms et al, 2007 ; Moraes et al, 2021 ).…”