Abstract

The neurotransmission of the chemoreflex in the nucleus tractus solitarii (NTS), particularly of the sympatho-excitatory component, is not completely understood. There is evidence that substance P may play a role in the neurotransmission of the chemoreflex in the NTS. Microinjection of substance P (50 pmol/50 nl, N = 12, and 5 nmol/50 nl, N = 8) into the commissural NTS of unanesthetized rats produced a significant increase in mean arterial pressure (101 +/- 1 vs 108 +/- 2 and 107 +/- 3 vs 115 +/- 4 mmHg, respectively) and no significant changes in heart rate (328 +/- 11 vs 347 +/- 15 and 332 +/- 7 vs 349 +/- 13 bpm, respectively) 2 min after microinjection. Previous treatment with WIN, an NK-1 receptor antagonist (2.5 nmol/50 nl), microinjected into the NTS of a specific group of rats, blocked the pressor (11 +/- 5 vs 1 +/- 2 mmHg) and tachycardic (31 +/- 6 vs 4 +/- 3 bpm) responses to substance P (50 pmol/50 nl, N = 5) observed 10 min after microinjection. Bilateral microinjection of WIN into the lateral commissural NTS (N = 8) had no significant effect on the pressor (50 +/- 4 vs 42 +/- 6 mmHg) or bradycardic (-230 +/- 16 vs -220 +/- 36 bpm) responses to chemoreflex activation with potassium cyanide (iv). These data indicate that the activation of NK-1 receptors by substance P in the NTS produces an increase in baseline mean arterial pressure and heart rate. However, the data obtained with WIN suggest that substance P and NK-1 receptors do not play a major role in the neurotransmission of the chemoreflex in the lateral commissural NTS.

Highlights

  • Studies from our laboratory have evaluated the autonomic processing of the cardiovascular reflexes in the nucleus tractus solitarii (NTS), with particular emphasis on the role of excitatory amino acid (EAA) receptors [1,2,3,4,5,6]

  • Considering that these two doses of substance P produced a similar increase in mean arterial pressure (MAP), it is possible that both are in the maximal dose range and for this reason we used the dose of 50 pmol/50 nl in the subsequent experiments

  • The NTS is the site of termination of arterial baroreceptors, carotid chemoreceptors and cardiopulmonary afferents (Bezold-Jarisch reflex) in the brainstem and different subpopulations of postsynaptic neurons in the NTS are involved in the autonomic responses to the activation of these cardiovascular reflexes

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Summary

Introduction

Studies from our laboratory have evaluated the autonomic processing of the cardiovascular reflexes in the nucleus tractus solitarii (NTS), with particular emphasis on the role of excitatory amino acid (EAA) receptors [1,2,3,4,5,6]. Considering the possible involvement of substance P in the processing of the sympatho-excitatory component of the chemoreflex in the NTS [11,12,13,14], in the present study we evaluated the role of substance P and NK-1 receptors in the processing of the chemoreflex afferents in the lateral commissural NTS of awake rats. To achieve these goals we microinjected substance P into the NTS of awake rats before and after local microinjection of WIN, an NK-1 receptor antagonist, and we activated the chemoreflex before and after bilateral microinjection of an effective dose of WIN into the lateral commissural NTS of awake rats. A preliminary report of these data has been published as an abstract [16]

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