Inhibitory modulation of chemoreflex bradycardia by stimulation of the nucleus raphe obscurus is mediated by 5-HT3 receptors in the NTS of awake rats.
Several studies demonstrated the involvement of 5-hydroxytryptamine (5-HT) and its different receptor subtypes in the modulation of neurotransmission of cardiovascular reflexes in the nucleus tractus solitarii (NTS). Moreover, anatomic evidence suggests that nucleus raphe obscurus (ROb) is a source of 5-HT-containing terminals within the NTS. In the present study we investigated the possible changes in the cardiovascular responses to peripheral chemoreceptor activation by potassium cyanide (KCN, i.v.) following ROb stimulation with L-glutamate (10 nmol/50 nL) and also whether 5-HT3 receptors in the caudal commissural NTS are involved in this neuromodulation. The results showed that stimulation of the ROb with L-glutamate in awake rats (n=15) produced a significant reduction in the bradycardic response 30 s after the microinjection (-182+/-19 vs -236+/-10 bpm; Wilcoxon test) but no changes in the pressor response to peripheral chemoreceptor activation (43+/-4 vs 51+/-3 mmHg; two-way ANOVA) in relation to the control. Microinjection of 5--HT3 receptors antagonist granisetron (500 pmol/50 nL), but not the vehicle, into the caudal commissural NTS bilaterally prevented the reduction of chemoreflex bradycardia in response to microinjection of L-glutamate into ROb. These data indicate that 5-HT-containing projections from ROb to the NTS play an inhibitory neuromodulatory role in the chemoreflex evoked bradycardia by releasing 5-HT and activating 5-HT3 receptors in the caudal NTS.
Weissheimer
Karin Viana
KV
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
Machado
Benedito H
BH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D003243:Consciousness; D018698:Glutamic Acid / Q000008:administration & dosage; D017829:Granisetron / Q000008:administration & dosage; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D009434:Neural Pathways / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000008:administration & dosage; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*
D018698:Glutamic Acid; D017829:Granisetron; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists