{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:58:54Z","timestamp":1760576334068,"version":"build-2065373602"},"reference-count":57,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Myocardial ischemia causes the release of bradykinin, which activates afferent nerve endings in the ventricular epicardium. This elicits a sympathetically mediated increase in arterial pressure and heart rate, referred to as the cardiogenic sympathetic afferent reflex. The rostroventrolateral medulla (RVLM) is a key sympathetic brain stem site for regulating cardiovascular activity. This study aimed to determine the importance of non\u2010barosensitive nociception sympathetic activity and the role of glutamate receptor activation of RVLM neurons in the cardiogenic sympathetic afferent reflex. We tested the hypothesis that inhibition of barosensitive sympathetic activity attenuates but does not abolish the reflex response to cardiac visceral afferents. Renal sympathetic nerve activity (RSNA), arterial pressure, and heart rate responses to epicardial bradykinin application were recorded in anesthetized rats before and after bilateral RVLM microinjection of either GABA<jats:sub>A<\/jats:sub> agonist muscimol, ionotropic glutamate receptor antagonist kynurenic acid, N\u2010methyl\u2010d\u2010aspartate (NMDA) receptor antagonist 2\u2010amino\u20105\u2010 phosphonopentanoic acid (AP5), or non\u2010NMDA antagonist 6\u2010cyano\u20107\u2010nitroquinoxaline\u20102,3\u2010dione (CNQX). Baroreceptor loading\u2010induced inhibition of barosensitive activity attenuated the bradykinin\u2010induced RSNA response (93\u2009\u00b1\u200914% increase) and tachycardia (18\u2009\u00b1\u20093\u2009bpm). While RVLM muscimol microinjection abolished the RSNA response (1.6\u2009\u00b1\u20094.2% from baseline, 0.49\u2009\u00b1\u20090.38\u2009\u03bcV*s), surprisingly, it did not abolish the tachycardia (27\u2009\u00b1\u20094\u2009bpm). Kynurenic acid microinjection blocked the arterial pressure and RSNA responses, while AP5 or CNQX only attenuated the responses. These data suggest that nociception\u2010sensitive sympathetic activity that does not appear to be barosensitive is also involved in the cardiogenic sympathetic afferent reflex. Importantly, while muscimol and kynurenic acid abolished the arterial pressure and RSNA response, neither affected the tachycardia, suggesting an alternate cardiac pathway independent of RVLM.<\/jats:p>","DOI":"10.1096\/fba.2024-00040","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T05:18:57Z","timestamp":1724044737000},"page":"377-389","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activation of nociception\u2010sensitive ionotropic glutamate receptor\u2010expressing rostroventrolateral medulla neurons by stimulation of cardiac afferents in rats"],"prefix":"10.1096","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0947-2103","authenticated-orcid":false,"given":"Matthew R.","family":"Zahner","sequence":"first","affiliation":[{"name":"Department of Health Sciences, College of Public Health East Tennessee State University  Johnson City Tennessee 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