Involvement of L-glutamate and ATP in the neurotransmission of the sympathoexcitatory component of the chemoreflex in the commissural nucleus tractus solitarii of awake rats and in the working heart-brainstem preparation.
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.
Braga
Valdir A
VA
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
Soriano
Renato N
RN
Braccialli
Alex L
AL
de Paula
Patrícia M
PM
Bonagamba
Leni G H
LG
Paton
Julian F R
JF
Machado
Benedito H
BH
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006339:Heart Rate; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D011190:Potassium Cyanide / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D015656:Respiratory Mechanics; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014851:Wakefulness
D000959:Antihypertensive Agents; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D009599:Nitroprusside; D018698:Glutamic Acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D007736:Kynurenic Acid; D011190:Potassium Cyanide; C002630:alpha,beta-methyleneadenosine 5'-triphosphate