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Bed nucleus of the stria terminalis modulates baroreflex cardiac activity: an interaction between alpha-1 receptors and NMDA/nitric oxide pathway

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Abstract

The bed nucleus of the stria terminalis (BNST) is a forebrain structure, involved in the modulation of neuroendocrine, cardiovascular and autonomic responses. One of the responses is baroreflex activity, which consists in a neural mechanism responsible for keeping the blood pressure within a narrow range of variation. It has been reported that blockade of BNST α1-adrenoceptors increased the bradycardic component of baroreflex. In addition, such receptors are able to modulate glutamate release in this structure. Interestingly, BNST NMDA receptor antagonism and neuronal nitric oxide synthase (nNOS) inhibition led to the same effect of the α1-adrenoceptors blockade on baroreflex bradycardic response. Therefore, the hypothesis of the present study is that BNST noradrenergic transmission interacts with NMDA/NO pathway through α1 adrenoceptors to modulate the baroreflex activity. Male Wistar rats had stainless steel guide cannulas bilaterally implanted in the BNST. Subsequently, a catheter was inserted into the femoral artery for cardiovascular recordings, and into the femoral vein for assessing baroreflex activation. Injection of the noradrenaline reuptake inhibitor reboxetine in the BNST did not modify the tachycardic, but significantly decreased the bradycardic component of baroreflex. Administration of an α1, but not an α2 antagonist into the BNST prior to reboxetine prevented this effect. Likewise, previous injection of NMDA/NO pathway blockers inhibited the effect of reboxetine on bradycardic response. In conclusion, it was demonstrated for the first time the existence of an interaction between BNST noradrenergic, glutamatergic and nitrergic neurotransmissions in the modulation of bradycardic baroreflex response.

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Acknowledgements

The authors wish to thank Camargo, L.H.A. and Mesquita O. for technical support.

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Funding

This study was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (Protocol number 461/2009); the Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq) (Protocol number 156718/2012-0); the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) fellowship and the Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da FMRP-USP (FAEPA).

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Davi C. Lagatta. and Leonardo Resstel conceived and designed this research; experiments were performed by Davi, Campos Lagatta., Luciana Bärg Kuntze, Daniela.Lescano Uliana and Anna Bárbara Borges Asis. Data were analysed by Davi Campos Lagatta., Luciana Bärg Kuntze and Leonardo Resstel. Results of experiments were interpreted by Davi Campos Lagatta., Luciana Bärg Kuntze and Leonardo Rresstel. Figures were prepared and manuscript was firstly drafted by Davi Campos Lagatta. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Leonardo B. M. Resstel.

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Experimental procedures were carried out following protocols approved by the Ethical Review Committee of the School of Medicine of Ribeirão Preto (Protocol number 019/2015), which complies with the Guiding Principles for Research Involving Animals and Human Beings of the American Physiological Society.

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Lagatta, D.C., Kuntze, L.B., Uliana, D.L. et al. Bed nucleus of the stria terminalis modulates baroreflex cardiac activity: an interaction between alpha-1 receptors and NMDA/nitric oxide pathway. Pflugers Arch - Eur J Physiol 473, 253–271 (2021). https://doi.org/10.1007/s00424-020-02475-1

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