alpha(1)- and alpha(2)-adrenergic receptors in the retrotrapezoid nucleus differentially regulate breathing in anesthetized adult rats

Author(s)

Oliveira, Luiz M. ; Moreira, Thiago S. ; Kuo, Fu-Shan ; Mulkey, Daniel K. ; Takakura, Ana C.

• Document type: Journal article
• Source: Journal of Neurophysiology; v. 116, n. 3, p. 1036-1048, SEP 2016.
• Web of Science Citations: 10

Abstract

Norepinephrine (NE) is a potent modulator of breathing that can increase/decrease respiratory activity by alpha(1)-/alpha(2)-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 (alpha(2)-AR agonist) blunted diaphragm muscle activity (Dia EMG) frequency and amplitude, without changing abdominal muscle activity. Those inhibitory effects were reduced by preapplication of yohimbine (alpha(2)-AR antagonist) into the RTN. Conversely, unilateral RTN injection of phenylephrine (alpha(1)-AR agonist) increased Dia EMG amplitude and frequency and facilitated active expiration. This response was blocked by prior RTN injection of prazosin (alpha(1)-AR antagonist). Interestingly, RTN injection of propranolol (beta-AR antagonist) had no effect on respiratory inhibition elicited by applications of NE into the RTN; however, the combined blockade of alpha(2)- and beta-ARs (coapplication of propranolol and yohimbine) revealed an alpha(1)-AR-dependent excitatory response to NE that resulted in increase in Dia EMG frequency and facilitation of active expiration. However, blockade of alpha(1)-, alpha(2)-, or beta-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. (AU)

• FAPESP's process: 13/10573-8 - Ventral surface chemoreceptor neuronal mechanisms
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/26540-1 - Noradrenergic mechanisms in the retrotrapezoid nucleus in the control of chemoreception
• Grantee: Luiz Marcelo Oliveira Santos
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/22406-1 - Respiratory anatomofunctional changes observed in an experimental model of Parkinson Disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Regular Research Grants