scholarly journals Generation of active expiration by serotoninergic mechanisms of the ventral medulla of rats

2016 ◽  
Vol 121 (5) ◽  
pp. 1135-1144 ◽  
Author(s):  
Eduardo V. Lemes ◽  
Eduardo Colombari ◽  
Daniel B. Zoccal
Keyword(s):  
Adult Male ◽  
Intermittent Hypoxia ◽  
Abdominal Muscle ◽  
Receptor Antagonism ◽  
Retrotrapezoid Nucleus ◽  
Agonist And Antagonist ◽  
Parafacial Respiratory Group ◽  
Spontaneously Breathing ◽  
Long Term Facilitation

Abdominal expiratory activity is absent at rest and is evoked during metabolic challenges, such as hypercapnia and hypoxia, or after the exposure to intermittent hypoxia (IH). The mechanisms engaged during this process are not completely understood. In this study, we hypothesized that serotonin (5-HT), acting in the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG), is able to generate active expiration. In anesthetized (urethane, ip), tracheostomized, spontaneously-breathing adult male Holtzman rats we microinjected a serotoninergic agonist and antagonist bilaterally in the RTN/pFRG and recorded diaphragm and abdominal muscle activities. We found that episodic (3 times, 5 min apart), but not single microinjections of 5-HT (1 mM) in the RTN/pFRG elicited an enduring (>30 min) increase in abdominal activity. This response was amplified in vagotomized rats and blocked by previous 5-HT receptor antagonism with ketanserin (10 µM). Episodic 5-HT microinjections in the RTN/pFRG also potentiated the inspiratory and expiratory reflex responses to hypercapnia. The antagonism of 5-HT receptors in the RTN/pFRG also prevented the long-term facilitation (>30 min) of abdominal activity in response to acute IH exposure (10 × 6–7% O for 45 s every 5 min). Our findings indicate the activation of serotoninergic mechanisms in the RTN/pFRG is sufficient to increase abdominal expiratory activity at resting conditions and required for the emergence of active expiration after IH in anesthetized animals.

scholarly journals Ventilatory long-term facilitation is evident after initial and repeated exposure to intermittent hypoxia in mice genetically depleted of brain serotonin

2014 ◽  
Vol 116 (3) ◽  
pp. 240-250 ◽  
Author(s):  
Stephen Hickner ◽  
Najaah Hussain ◽  
Mariana Angoa-Perez ◽  
Dina M. Francescutti ◽  
Donald M. Kuhn ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Intermittent Hypoxia ◽  
Tryptophan Hydroxylase ◽  
Breathing Frequency ◽  
Wild Type ◽  
Tryptophan Hydroxylase 2 ◽  
Daily Exposure ◽  
Spontaneously Breathing ◽  
Long Term Facilitation

Our study was designed to determine if central nervous system (CNS) serotonin is required for the induction of ventilatory long-term facilitation (LTF) in intact, spontaneously breathing mice. Nineteen tryptophan hydroxylase 2-deficient (Tph2−/−) mice, devoid of serotonin in the CNS, and their wild-type counterparts (Tph2+/+) were exposed to intermittent hypoxia each day for 10 consecutive days. The ventilatory response to intermittent hypoxia was greater in the Tph2+/+ compared with the Tph2−/− mice (1.10 ± 0.10 vs. 0.77 ± 0.01 ml min−1·percent−1 oxygen; P ≤ 0.04). Ventilatory LTF, caused by increases in breathing frequency, was evident in Tph2+/+ and Tph2−/− mice following exposure to intermittent hypoxia each day; however, the magnitude of the response was greater in the Tph2+/+ compared with the Tph2−/− mice (1.11 ± 0.02 vs. 1.05 ± 0.01 normalized to baseline on each day; P ≤ 0.01). The magnitude of ventilatory LTF increased significantly from the initial to the finals days of the protocol in the Tph2−/− (1.06 ± 0.02 vs. 1.11 ± 0.03 normalized to baseline on the initial days; P ≤ 0.004) but not in the Tph2+/+ mice. This enhanced response was mediated by increases in tidal volume. Body temperature and metabolic rate did not account for differences in the magnitude of ventilatory LTF observed between groups after acute and repeated daily exposure to intermittent hypoxia. We conclude that ventilatory LTF, after acute exposure to intermittent hypoxia, is mediated by increases in breathing frequency and occurs in the absence of serotonin, although the magnitude of the response is diminished. This weakened response is enhanced following repeated daily exposure to intermittent hypoxia, via increases in tidal volume, to a similar magnitude evident in Tph2+/+ mice. Thus the magnitude of ventilatory LTF following repeated daily exposure to intermittent hypoxia is not dependent on the presence of CNS serotonin.

Selected Contribution: Chronic intermittent hypoxia enhances respiratory long-term facilitation in geriatric female rats

2003 ◽  
Vol 95 (6) ◽  
pp. 2614-2623 ◽  
Author(s):  
A. G. Zabka ◽  
G. S. Mitchell ◽  
E. B. Olson ◽  
M. Behan
Keyword(s):  
Intermittent Hypoxia ◽  
Young Female ◽  
Time Dependent ◽  
Female Rats ◽  
Chronic Intermittent Hypoxia ◽  
Middle Aged ◽  
Short Term ◽  
Hypoxic Response ◽  
Long Term Facilitation

Age and the estrus cycle affect time-dependent respiratory responses to episodic hypoxia in female rats. Respiratory long-term facilitation (LTF) is enhanced in middle-aged vs. young female rats ( 72 ). We tested the hypothesis that phrenic and hypoglossal (XII) LTF are diminished in acyclic geriatric rats when fluctuating sex hormone levels no longer establish conditions that enhance LTF. Chronic intermittent hypoxia (CIH) enhances LTF ( 41 ); thus we further predicted that CIH would restore LTF in geriatric female rats. LTF was measured in young (3-4 mo) and geriatric (20-22 mo) female Sasco Sprague-Dawley rats and in a group of geriatric rats exposed to 1 wk of nocturnal CIH (11 vs. 21% O2 at 5-min intervals, 12 h/night). In anesthetized, paralyzed, vagotomized, and ventilated rats, time-dependent hypoxic phrenic and XII responses were assessed. The short-term hypoxic response was measured during the first of three 5-min episodes of isocapnic hypoxia (arterial Po2 35-45 Torr). LTF was assessed 15, 30, and 60 min postepisodic hypoxia. Phrenic and XII short-term hypoxic response was not different among groups, regardless of CIH treatment ( P > 0.05). LTF in geriatric female rats was smaller than previously reported for middle-aged rats but comparable to that in young female rats. CIH augmented phrenic and XII LTF to levels similar to those of middle-aged female rats without CIH ( P < 0.05). The magnitude of phrenic and XII LTF in all groups was inversely related to the ratio of progesterone to estradiol serum levels ( P < 0.05). Thus CIH and sex hormones influence the magnitude of LTF in geriatric female rats.

Mechanisms of severe acute intermittent hypoxia-induced phrenic long-term facilitation

2021 ◽  
Vol 125 (4) ◽  
pp. 1146-1156
Author(s):  
Nicole L. Nichols ◽  
Gordon S. Mitchell
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Intermittent Hypoxia ◽  
Nadph Oxidase Activity ◽  
Complex Interactions ◽  
Long Term Facilitation ◽  
Erk Activity

Distinct mechanisms give rise to pLTF induced by moderate and severe AIH. We demonstrate that, unlike moderate AIH, severe AIH-induced pLTF requires EPAC and PI3K/Akt and is marginally constrained by NADPH oxidase activity. Surprisingly, sAIH-induced pLTF requires MEK/ERK activity similar to moderate AIH-induced pLTF and is reduced by PKA inhibition. We suggest sAIH-induced pLTF arises from complex interactions between dominant mechanisms characteristic of moderate versus severe AIH-induced pLTF.

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