Respiratory Network Enhances the Sympathoinhibitory Component of Baroreflex of Rats Submitted to Chronic Intermittent Hypoxia

Abstract

C hronic intermittent hypoxia (CIH) is characterized by frequent activation of the peripheral chemoreceptors, which over time produces several cardiovascular dysfunctions, including mild hypertension. [1][2][3][4] The CIH-induced hypertension in rats can be prevented by sympathetic nerve chemical denervation, renal sympathectomy, and adrenal medullectomy. 1,5,6 Rats submitted to CIH also presented a larger fall in arterial pressure in response to ganglionic blockade and augmented power of oscillatory components at low and high frequencies in systolic arterial pressure.7 All these evidences indicate that hypertension in CIH rats is mediated through sympathetic overactivity. However, the mechanisms by which CIH produces sympathetic overactivity and hypertension are not yet characterized.The central generator of respiration in the brain stem modulates the activity of presympathetic neurons in the rostral ventrolateral medulla (RVLM), [8][9][10] GABAergic RVLM-projecting neurons in the caudal ventrolateral medulla (CVLM), 11 and the sympathetic nerves, 3,12-14 affecting cardiovascular function. Therefore, changes in the respiratory-related sympathetic activity after CIH may contribute to mechanisms underlying the sympathetic overactivity and hypertension in rats. In this regard, we previously demonstrated that hypertensive CIH rats exhibited increased expiratory-related firing frequency of barosensitive RVLM presympathetic neurons 9 and sympathetic activity, 3,4 which were generated by enhanced synaptic inputs from expiratory neurons. 9 These data suggest that sympathetic overactivity after CIH is because of changes in the pattern of respiratory rhythm generator and its central modulation of sympathetic outflow.Previous studies [15][16][17][18] proposed that reduction in baroreflex gain also plays an important role in the development of sympathetic overactivity and hypertension after several days of CIH. However, studies by Lai et al 16 demonstratedAbstract-Chronic intermittent hypoxia (CIH) produces respiratory-related sympathetic overactivity and hypertension in rats.In this study, we tested the hypothesis that the enhanced central respiratory modulation of sympathetic activity after CIH also decreases the sympathoinhibitory component of baroreflex of rats, which may contribute to the development of hypertension. Wistar rats were exposed to CIH or normoxia (control group) for 10 days. Phrenic nerve, thoracic sympathetic nerve, and neurons in the rostral ventrolateral medulla and caudal ventrolateral medulla were recorded in in situ preparations of rats. Baroreflex regulation of thoracic sympathetic nerve, rostral ventrolateral medulla, and caudal ventrolateral medulla neurons activities were evaluated in different phases of respiration in response to either aortic depressor nerve stimulation or pressure stimuli. CIH rats presented higher respiratory-related thoracic sympathetic nerve and rostral ventrolateral medulla presympathetic neurons activities at the end of expiration in relation to control rats, which are ...

Role of ventral medullary catecholaminergic neurons for respiratory modulation of sympathetic outflow in rats

“…RVLM neurons exhibit different patterns of activity entrained by the respiratory pattern generator, with peaks of activity modulated by either I or PI 19 , 22 , 36 – 38 . We showed that Alst inhibited TH-positive inspiratory-modulated, but not TH-negative post-inspiratory-modulated RVLM bulbo-spinal barosensitive pre-sympathetic neurons.…”

“…RVLM C1 and non-C1 neurons are both modulated by respiration 19 and both show increased respiratory-related activity during hypoxia or hypercapnia 20 , 21 . In this regard, our previous studies have demonstrated that rats submitted to chronic intermittent hypoxia (CIH) exhibit active expiration 10 and an increase in the firing frequency of expiratory-modulated pre-sympathetic RVLM C1 neurons 19 , 22 , which was also reflected in sympathetic post-ganglionic activity 10 . Indeed, we proposed that this expiratory-related sympathetic activity may contribute to the sustained hypertension induced by CIH in rats 23 .…”

Locus Coeruleus as a vigilance centre for active inspiration and expiration in rats

“…The correct placement of the guide cannula was confirmed at the end of the experiment by injection of Evans Blue (2% in 10 μl; Sigma-Aldrich, St. Louis, USA) and its visible presence in the intracerebroventricular system. After electrophysiological experiments, LC neurons were filled with biocytin using the previously described juxtacellular labelling method (200 ms pulses of 1.0–4.0 nA at 2.5 Hz for 1–3 min) 70 . All signals were acquired by a data acquisition system (5 KHz; CED 1401; Cambridge Electronic Design, UK) controlled by a computer running Spike 2 software (Cambridge Electronic Design).…”

Cardiovascular and respiratory profiles during the sleep–wake cycle of rats previously submitted to chronic intermittent hypoxia

“…Chronic intermittent hypoxia (CIH) is an experimental model of repetitive peripheral chemoreceptor activation (Braga, Soriano, & Machado, ; Fletcher, ; Fletcher et al., ; Moraes et al., ; Prabhakar, Peng, Jacono, Kumar, & Dick, ; Zoccal, Bonagamba, Oliveira, Antunes‐Rodrigues, & Machado, , Zoccal, Bonagamba, Paton, & Machado, ). Long‐term exposure to intermittent hypoxia has been shown to lead to sustained hypertension in male and female rats (Fletcher et al., ; Moraes et al., ; Perim, Bonagamba, & Machado, ; Souza, Bonagamba, Amorim, Moraes, & Machado, , ; Souza, Amorim, Moraes, & Machado, ; Zoccal, Bonagamba, Antunes‐Rodrigues, & Machado, , Zoccal et al., 2007b, , ).…”