Central chemoreceptors and sympathetic vasomotor outflow

Abstract

The present study explores how elevations in brain P CO 2 increase the sympathetic nerve discharge (SND). SND, phrenic nerve discharge (PND) and putative sympathoexcitatory vasomotor neurons of the rostral ventrolateral medulla (RVLM) were recorded in anaesthetized sino-aortic denervated and vagotomized rats. Hypercapnia (end-expiratory CO 2 from 5% to 10%) increased SND (97 ± 6%) and the activity of RVLM neurons (67 ± 4%). Injection of kynurenic acid (Kyn, ionotropic glutamate receptor antagonist) into RVLM or the retrotrapezoid nucleus (RTN) eliminated or reduced PND, respectively, but did not change the effect of CO 2 on SND. Bilateral injection of Kyn or muscimol into the rostral ventral respiratory group (rVRG-pre-Bötzinger region, also called CVLM) eliminated PND while increasing the stimulatory effect of CO 2 on SND. Muscimol injection into commissural part of the solitary tract nucleus (commNTS) had no effect on PND or SND activation by CO 2 . As expected, injection of Kyn into RVLM or muscimol into commNTS virtually blocked the effect of carotid body stimulation on SND in rats with intact carotid sinus nerves. In conclusion, CO 2 increases SND by activating RVLM sympathoexcitatory neurons. The relevant central chemoreceptors are probably located within or close to RVLM and not in the NTS or in the rVRG-pre-Bötzinger/CVLM region. RVLM sympathoexcitatory neurons may be intrinsically pH-sensitive and/or receive excitatory synaptic inputs from RTN chemoreceptors. Activation of the central respiratory network reduces the overall sympathetic response to CO 2 , presumably by activating barosensitive CVLM neurons and inhibiting RTN chemoreceptors.

Mecanismos purinérgicos no bulbo ventrolateral rostral modulam respostas cardiovasculares e respiratórias promovidas pela ativação dos quimiorreceptores centrais e periféricos.

“…Similarly, MRS2179 also decreased peripheral chemoreceptor activation of PNA amplitude and frequency by 25±6% (P=0.037; Figure 2A and 2E) and 33±7% (P=0.032; Figure 2A and 2F), respectively. Consistent with previous evidence, 36 bilateral RVLM injec tions of kynurenic acid decreased baseline PNA amplitude by guest on August 12, 2014 http://hyper.ahajournals.org/ Downloaded from (59±5%) and increased PNA frequency (46±4%), but did not affect sSNA or MAP. Injections of kynurenic acid into the RVLM also blunted the peripheral chemoreceptor-mediated increase in breathing amplitude, SNA, and blood pressure (Figure 2A, 2C-2F).…”

“…Specifically, we show in anesthetized rats that bilat eral injections of kynurenic acid significantly decreased the ventilatory, sympathetic, and pressor responses to peripheral chemoreceptor activation. These results are consistent with pre vious studies that used kynurenic acid 36 or APV ([2R]amino5 phosphonovaleric acid; specific Nmethyldaspartate receptor blocker) 48 to attenuate the response of RVLM presympathetic cells to peripheral chemoreceptor drive. In addition, we found that the majority of NTS terminals in the RVLM were immuno reactive for VGLUT2 (77%).…”

“…We found that C1lesioned animals showed attenuation in the SNA and MAP, but not in PNA amplitude or frequency, responses elic ited by cyanide ( Figure 7A, 7D-7G), suggesting that C1 cells are key determinants of the sympathoexcitatory response to peripheral chemoreceptor activation. Although C1 cells also contribute to the peripheral chemoreceptor ventilatory reflex, 36 the cyanideinduced ventilatory responses were retained in C1lesioned animals suggesting compensation by other com ponents of the respiratory circuit (eg, chemosensitive RTN neurons).…”

Envolvimento do núcleo Kölliker-Fuse e do núcleo parabraquial lateral no controle cardiorrespiratório promovido pela ativação dos quimiorreceptores centrais e periféricos.

“…3) localização e exposição do nervo frênico e do nervo esplâncnico via posição dorsolateral (MOREIRA et al, 2006;MOREIRA, 2013;TAKAKURA et al, 2006;TAKAKURA et al, 2008;TAKAKURA et al, 2007) …”

Neurônios catecolaminérgicos do tronco encefálico participam dos ajustes respiratórios induzidos por hipóxia e hipercapnia.

“…Embora seja crescente o número de trabalhos postulando que núcleos de células quimiossensíveis estejam distribuídos ao longo do encéfalo (Nattie, Li, 2010), é comumente aceito que o núcleo retrotrapezóide (RTN), localizado na porção ventral ao núcleo motor do núcleo facial e próximo da superfície ventrolateral do bulbo (Connelly et al, 1989;Connelly et al, 1990;Mulkey et al, 2004;Takakura et al, 2006), concentre o principal grupamento de células quimiorreceptoras centrais. Além disso, essa região está localizada próxima do grupamento catecolaminérgico C1 (Mulkey et al, 2004;Moreira et al, 2006;Lazarenko et al, 2009). Esta organização anátomo-funcional sugere uma integração entre o quimiorreflexo periférico e central, a regulação da respiração e funções autônomas (Rosin et al, 2006;Takakura et al, 2006).…”