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This Article Full Text Full Text (PDF) All Versions of this Article: 581/3/1129    most recent jphysiol.2007.129031v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Braga, V. A. Articles by Machado, B. H. Search for Related Content PubMed PubMed Citation Articles by Braga, V. A. Articles by Machado, B. H. Related Collections Cardiovascular

¹ Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo-USP, 14049-900, Ribeirão Preto, SP, Brazil
² Department of Physiology and Pathology, School of Dentistry, São Paulo State University-UNESP, 14801-903, Araraquara, SP, Brazil
³ Department of Physiology, Bristol Heart Institute, School of Medical Sciences, University of Bristol, Bristol BS8 2TD, UK

Peripheral chemoreflex activation with potassium cyanide (KCN) in awake rats or in the working heart–brainstem preparation (WHBP) produces: (a) a sympathoexcitatory/pressor response; (b) bradycardia; and (c) an increase in the frequency of breathing. Our main aim was to evaluate neurotransmitters involved in mediating the sympathoexcitatory component of the chemoreflex within the nucleus tractus solitarii (NTS). In previous studies in conscious rats, the reflex bradycardia, but not the pressor response, was reduced by antagonism of either ionotropic glutamate or purinergic P2 receptors within the NTS. In the present study we evaluated a possible dual role of both P2 and NMDA receptors in the NTS for processing the sympathoexcitatory component (pressor response) of the chemoreflex in awake rats as well as in the WHBP. Simultaneous blockade of ionotropic glutamate receptors and P2 receptors by sequential microinjections of kynurenic acid (KYN, 2 nmol (50 nl)^–1) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonate (PPADS, 0.25 nmol (50 nl)^–1) into the commissural NTS in awake rats produced a significant reduction in both the pressor (+38 ± 3 versus +8 ± 3 mmHg) and bradycardic responses (–172 ± 18 versus –16 ± 13 beats min^–1; n = 13), but no significant changes in the tachypnoea measured using plethysmography (270 ± 30 versus 240 ± 21 cycles min^–1, n = 7) following chemoreflex activation in awake rats. Control microinjections of saline produced no significant changes in these reflex responses. In WHBP, microinjection of KYN (2 nmol (20 nl)^–1) and PPADS (1.6 nmol (20 nl)^–1) into the commissural NTS attenuated significantly both the increase in thoracic sympathetic activity (+52 ± 2% versus +17 ± 1%) and the bradycardic response (–151 ± 17 versus –21 ± 3 beats min^–1) but produced no significant changes in the increase of the frequency of phrenic nerve discharge (+0.24 ± 0.02 versus +0.20 ± 0.02 Hz). The data indicate that combined microinjections of PPADS and KYN into the commissural NTS in both awake rats and the WHBP are required to produce a significant reduction in the sympathoexcitatory response (pressor response) to peripheral chemoreflex activation. We conclude that glutamatergic and purinergic mechanisms are part of the complex neurotransmission system of the sympathoexcitatory component of the chemoreflex at the level of the commissural NTS.

(Received 24 January 2007; accepted after revision 22 March 2007; first published online 29 March 2007)
Corresponding author B. H. Machado: Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil. Email: bhmachad{at}fmrp.usp.br