Functional interaction between nucleus tractus solitarius NK1 and 5-HT3 receptors in the inhibition of baroreflex in rats

Objective: Previous data showed that in the nucleus tractus solitatius (NITS), 5-HT3 receptors are critically involved in the inhibition of cardiac baroreceptor reflex response occurring during the defense reaction. Since stimulation of NTS NK1 receptors has been found to inhibit the baroreflex bradycardia, we examined in this study whether this reflex response is inhibited during the defense reaction via an interaction between NK1 and 5-HT3 receptors. Methods: For this purpose, we analyzed in urethane-anaesthetized rats the effects of intra-NTS GR205171, a selective NK1 receptor antagonist, on the baroreflex bradycardia inhibition observed either during the defense reaction triggered by electrical stimulation of the dorsal periaqueductal grey matter (dPAG) or after NTS 5-HT3 receptor activation. Results: Intra-NTS GR205171, reversed, in dose-dependent manner, the inhibitory effect of dPAG stimulation on baroreflex bradycardia. This reversion was of 49% when both sinus carotid and aortic baroreceptors were stimulated by phenylephrine, and of 84% when aortic depressor nerve was stimulated. Similarly, intra-NTS GR205171 reversed partially or almost totally the inhibitory effect of local microinjections of phenylbiguanide, a 5-HT3 receptor agonist, on baroreflex bradycardia induced either by phenylephrine administration or aortic nerve stimulation, respectively. Conclusion: These results strongly suggest that NK1 receptors contribute downstream to the 5-HT3 receptor-mediated inhibition of the aortic but not carotid cardiac baroreflex response occurring during the defense reaction, therefore implying that baroreceptor afferent inputs may be differentially modulated depending on their origin. This differentiation may be useful for a better understanding of baroreflex dysfunction in disease-induced conditions. (C) 2004 European Society of Cardiology. Published by Elsevier B.V All rights reserved.