--- _id: '747' abstract: - lang: eng text: Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation. BK produced a dose-dependent increase in cytosolic Ca2+ concentration. Pretreatment with HOE140, a B2 receptor antagonist, but not with R715, a B1 receptor antagonist, abolished the response to BK. A selective B2 receptor agonist, but not a B1 receptor agonist, elicited an increase in cytosolic Ca2+ similarly to BK. Inhibition of N-type voltage-gated Ca2+ channels with ω-conotoxin GVIA had no effect on the Ca2+ signal produced by BK, while pretreatment with ω-conotoxin MVIIC, a blocker of P/Q-type of Ca2+ channels, significantly diminished the effect of BK. Pretreatment with xestospongin C and 2-aminoethoxydiphenyl borate, antagonists of inositol 1,4,5-trisphosphate receptors, abolished the response to BK. Inhibition of ryanodine receptors reduced the BK-induced Ca2+ increase, while disruption of lysosomal Ca2+ stores with bafilomycin A1 did not affect the response. BK produced a dose-dependent depolarization of nucleus ambiguus neurons, which was prevented by the B2 receptor antagonist. In vivo studies indicate that microinjection of BK into nucleus ambiguus elicited bradycardia in conscious rats via B2 receptors. In summary, in cardiac vagal neurons of nucleus ambiguus, BK activates B2 receptors promoting Ca2+ influx and Ca2+ release from endoplasmic reticulum, and membrane depolarization; these effects are translated in vivo by bradycardia. article_processing_charge: No article_type: original author: - first_name: Eugen full_name: Brǎiloiu, Eugen last_name: Brǎiloiu - first_name: Matthew full_name: Mcguire, Matthew last_name: Mcguire - first_name: Shadaria full_name: Shuler, Shadaria last_name: Shuler - first_name: Elena full_name: Deliu, Elena id: 37A40D7E-F248-11E8-B48F-1D18A9856A87 last_name: Deliu orcid: 0000-0002-7370-5293 - first_name: Jeffrey full_name: Barr, Jeffrey last_name: Barr - first_name: Mary full_name: Abood, Mary last_name: Abood - first_name: Gabriela full_name: Brailoiu, Gabriela last_name: Brailoiu citation: ama: Brǎiloiu E, Mcguire M, Shuler S, et al. Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. 2017;365:23-32. doi:10.1016/j.neuroscience.2017.09.034 apa: Brǎiloiu, E., Mcguire, M., Shuler, S., Deliu, E., Barr, J., Abood, M., & Brailoiu, G. (2017). Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. Elsevier. https://doi.org/10.1016/j.neuroscience.2017.09.034 chicago: Brǎiloiu, Eugen, Matthew Mcguire, Shadaria Shuler, Elena Deliu, Jeffrey Barr, Mary Abood, and Gabriela Brailoiu. “Modulation of Cardiac Vagal Tone by Bradykinin Acting on Nucleus Ambiguus.” Neuroscience. Elsevier, 2017. https://doi.org/10.1016/j.neuroscience.2017.09.034. ieee: E. Brǎiloiu et al., “Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus,” Neuroscience, vol. 365. Elsevier, pp. 23–32, 2017. ista: Brǎiloiu E, Mcguire M, Shuler S, Deliu E, Barr J, Abood M, Brailoiu G. 2017. Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. 365, 23–32. mla: Brǎiloiu, Eugen, et al. “Modulation of Cardiac Vagal Tone by Bradykinin Acting on Nucleus Ambiguus.” Neuroscience, vol. 365, Elsevier, 2017, pp. 23–32, doi:10.1016/j.neuroscience.2017.09.034. short: E. Brǎiloiu, M. Mcguire, S. Shuler, E. Deliu, J. Barr, M. Abood, G. Brailoiu, Neuroscience 365 (2017) 23–32. date_created: 2018-12-11T11:48:17Z date_published: 2017-12-04T00:00:00Z date_updated: 2023-09-27T12:26:59Z day: '04' department: - _id: GaNo doi: 10.1016/j.neuroscience.2017.09.034 external_id: isi: - '000415966200003' pmid: - '28951324' intvolume: ' 365' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798458 month: '12' oa: 1 oa_version: Submitted Version page: 23 - 32 pmid: 1 publication: Neuroscience publication_identifier: issn: - '03064522' publication_status: published publisher: Elsevier publist_id: '6911' quality_controlled: '1' scopus_import: '1' status: public title: Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 365 year: '2017' ...