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Noradrenergic signaling in the retrotrapezoid nucleus differentially modulates breathing in anesthetized rats by alpha‐1 and alpha‐2 receptor dependent mechanisms
Author(s) -
Oliveira Luiz M,
Mulkey Daniel K,
Moreira Thiago,
Takakura Ana C
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.988.4
Subject(s) - yohimbine , alpha (finance) , endocrinology , agonist , medicine , chemistry , phenylephrine , imidazoline receptor , receptor , alpha 2 adrenergic receptor , moxonidine , antagonist , blood pressure , construct validity , nursing , patient satisfaction
Noradrenaline is a potent modulator of breathing that can increase or decrease respiratory activity by alpha‐1 or alpha‐2 receptors activation, respectively. The retrotrapezoid nucleus (RTN) is a region located in the rostral aspect of ventrolateral medulla and is known to contribute to central chemoreception, inspiration and active expiration. The aims of this study are to further investigate sources of catecholaminergic inputs to the RTN, as well as identify cardiorespiratory effects produced by activation of adrenergic receptors in this region. We identified a considerable number of the retrograde tracer FluorGold labeled cells (41 ± 8%) in the A7 region, suggesting the A7 is a major source of noradrenergic drive to the RTN. In urethane‐anesthetized, vagotomized and artificial ventilated male Wistar rats (260–290 g, n= 8–10/group), mean arterial pressure (MAP), diaphragm (Dia EMG ) and abdominal (Abd EMG ) muscle activities were recorded. Unilateral injection of noradrenaline produced a transient dose‐dependent (from 0.25 – 1 mM) inhibition of Dia EMG frequency (Δ = −10 ± 4; −14 ± 7 and −27 ± 11% of control) and amplitude (Δ = −41 ± 4.1; −48 ± 3% and −65 ± 2% of control), without changing MAP and Abd EMG . Unilateral injection of the alpha‐2 adrenergic and imidazoline receptors agonist moxonidine (20 μM) also produced a reduction in Dia EMG amplitude and frequency. The inhibition in the inspiratory activity produced by noradrenaline or moxonidine was completely blocked by the pretreatment with yohimbine (alpha‐2 receptors antagonist, 100 μM) in the RTN. We also found that unilateral RTN injection of phenylephrine (Phe, alpha‐1 adrenergic receptor agonist, 10 μM) increased Dia EMG amplitude by 62 ± 8% and frequency by 75 ± 18% and was able to elicit active expiration. The stimulatory effect on breathing produced by Phe was completely blocked by prior injection of prazosin (alpha‐1 receptor antagonist, 200 μM) into the RTN. We conclude that i) the pontine A7 region is a major source of cathecolamines to the RTN; ii) activation of alpha‐2 adrenergic receptors in the RTN inhibits respiratory activity; and iii) activation of alpha‐1 adrenergic receptors in the RTN increases inspiratory and expiratory activity. In related work, we have characterized the cellular and molecular mechanisms underlying noradrenaline modulation of RTN chemoreceptors (see abstract by Kuo et al.). Support or Funding Information FAPESP, CNPq, CAPES/PROEX