α1- and α2-adrenergic receptors in the retrotrapezoid nucleus differentially regulate breathing in anesthetized adult rats.
Norepinephrine (NE) is a potent modulator of breathing that can increase/decrease respiratory activity by α1-/α2-adrenergic receptor (AR) activation, respectively. The retrotrapezoid nucleus (RTN) is known to contribute to central chemoreception, inspiration, and active expiration. Here we investigate the sources of catecholaminergic inputs to the RTN and identify respiratory effects produced by activation of ARs in this region. By injecting the retrograde tracer Fluoro-Gold into the RTN, we identified back-labeled catecholaminergic neurons in the A7 region. In urethane-anesthetized, vagotomized, and artificially ventilated male Wistar rats unilateral injection of NE or moxonidine (α2-AR agonist) blunted diaphragm muscle activity (DiaEMG) frequency and amplitude, without changing abdominal muscle activity. Those inhibitory effects were reduced by preapplication of yohimbine (α2-AR antagonist) into the RTN. Conversely, unilateral RTN injection of phenylephrine (α1-AR agonist) increased DiaEMG amplitude and frequency and facilitated active expiration. This response was blocked by prior RTN injection of prazosin (α1-AR antagonist). Interestingly, RTN injection of propranolol (β-AR antagonist) had no effect on respiratory inhibition elicited by applications of NE into the RTN; however, the combined blockade of α2- and β-ARs (coapplication of propranolol and yohimbine) revealed an α1-AR-dependent excitatory response to NE that resulted in increase in DiaEMG frequency and facilitation of active expiration. However, blockade of α1-, α2-, or β-ARs in the RTN had minimal effect on baseline respiratory activity, on central or peripheral chemoreflexes. These results suggest that NE signaling can modulate RTN chemoreceptor function; however, endogenous NE signaling does not contribute to baseline breathing or the ventilatory response to central or peripheral chemoreceptor activity in urethane-anesthetized rats.
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil;
Luiz M
LM
Oliveira
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil; and.
Thiago S
TS
Moreira
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut.
Fu-Shan
FS
Kuo
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut.
Daniel K
DK
Mulkey
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil; takakura@icb.usp.br.
Ana C
AC
Takakura
D000200:Action Potentials / Q000187:drug effects; D018663:Adrenergic Agents / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D003964:Diaphragm / Q000502:physiology; D004791:Enzyme Inhibitors; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects; D012125:Respiratory Center / Q000166:cytology* / Q000000981:diagnostic imaging; D013266:Stilbamidines / Q000378:metabolism; D014628:Vagotomy
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D018663:Adrenergic Agents; D004791:Enzyme Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D013266:Stilbamidines; D011190:Potassium Cyanide; D009638:Norepinephrine
adrenergic receptors; inspiration; medulla oblongata; norepinephrine; retrotrapezoid nucleus