alpha1- and alpha2-adrenergic receptors in the retrotrapezoid nucleus differentially regulate breathing in anesthetized adult rats

• Grant number: 16/16170-0
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: September 01, 2016
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Carolina Takakura Moreira
• Grantee: Ana Carolina Takakura Moreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Norepinephrine (NE) is a potent modulator of breathing that can increase/decrease respiratory activity by alpha1/alpha2-adrenergic receptor (AR) activation, respectively. The retrotrapezoid nucleus (RTN) is known to contribute to central chemoreception, inspiration, and active expiration. Here we investigate thesources of catecholaminergic inputs to the RTN and identify respiratory effects produced by activation of ARs in this region. By injectingthe retrograde tracer Fluoro-Gold into the RTN, we identified backlabeled catecholaminergic neurons in the A7 region. In urethaneanesthetized, vagotomized, and artificially ventilated male Wistar ratsunilateral injection of NE or moxonidine (2-AR agonist) blunted diaphragm muscle activity (DiaEMG) frequency and amplitude, without changing abdominal muscle activity. Those inhibitory effects were reduced by preapplication of yohimbine (alpha2-AR antagonist) into the RTN. Conversely, unilateral RTN injection of phenylephrine (alpha1-AR agonist) increased DiaEMGamplitude and frequency and facilitated active expiration. This response was blocked by prior RTN injection of prazosin (alpha1-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 alpha2- and beta-ARs (coapplication of propranolol and yohimbine) revealed an alpha1-AR-dependent excitatory response to NE that resulted in increase in DiaEMG frequency and facilitation of activeexpiration. However, blockade of alpha1-,alpha2-, or beta-ARs in the RTN hadminimal effect on baseline respiratory activity, on central or peripheral chemoreflexes. These results suggest that NE signaling can modulate RTN chemoreceptor function; however, endogenous NEsignaling does not contribute to baseline breathing or the ventilatoryresponse to central or peripheral chemoreceptor activity in urethaneanesthetized rats. (AU)