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We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a \u03b1<jats:sub>2<\/jats:sub>\u2010adrenergic receptor agonist, dexmedetomidine (10\u00a0min loading infusion of 0.225\u00a0\u00b5g\u00a0kg<jats:sup>\u22121<\/jats:sup>; maintenance infusion of 0.1\u20130.5\u00a0\u00b5g\u00a0kg\u00a0h<jats:sup>\u22121<\/jats:sup>) in eight healthy individuals (28\u00a0\u00b1\u00a07\u00a0years, five females). Dexmedetomidine reduced mean pressure (92\u00a0\u00b1\u00a07 to 80\u00a0\u00b1\u00a08\u00a0mmHg, <jats:italic>P<\/jats:italic> &lt; 0.001) but did not alter heart rate (61\u00a0\u00b1\u00a013 to 60\u00a0\u00b1\u00a014\u00a0bpm; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.748). Dexmedetomidine reduced sympathetic AP discharge (126\u00a0\u00b1\u00a073 to 27\u00a0\u00b1\u00a024 AP\u00a0100 beats<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003) most strongly for medium\u2010sized APs (normalized cluster 2: 21\u00a0\u00b1\u00a010 to 5\u00a0\u00b1\u00a05 AP\u00a0100 beats<jats:sup>\u22121<\/jats:sup>; <jats:italic>P<\/jats:italic> &lt; 0.001). Dexmedetomidine progressively de\u2010recruited sympathetic APs beginning with the largest AP clusters (12\u00a0\u00b1\u00a03 to 7\u00a0\u00b1\u00a02 clusters, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002). Despite de\u2010recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18\u00a0\u00b1\u00a00.12 to 1.13\u00a0\u00b1\u00a00.13\u00a0s, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002). A subset of six participants performed a Valsalva manoeuvre (20\u00a0s, 40\u00a0mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (\u0394\u00a0361\u00a0\u00b1\u00a0292 to \u0394\u00a0113\u00a0\u00b1\u00a0155 AP\u00a0100 beats<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (\u0394\u00a02\u00a0\u00b1\u00a01 to \u0394\u00a00\u00a0\u00b1\u00a02 AP clusters, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (\u0394\u00a0\u20130.09\u00a0\u00b1\u00a00.07 to \u0394\u00a0\u20130.07\u00a0\u00b1\u00a00.14\u00a0s, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium\u2010sized APs (normalized cluster 2: \u20136.0\u00a0\u00b1\u00a05 to \u20131.6\u00a0\u00b1\u00a02 %\u00a0mmHg<jats:sup>\u22121<\/jats:sup>; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.008). These data suggest that \u03b1<jats:sub>2<\/jats:sub>\u2010adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16224-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This microneurographic study investigated the impact of a dexmedetomidine infusion (\u03b1<jats:sub>2<\/jats:sub>\u2010adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data suggest that \u03b1<jats:sub>2<\/jats:sub>\u2010adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp286450","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T17:33:12Z","timestamp":1722015192000},"page":"4053-4071","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Central \u03b1<sub>2<\/sub>\u2010adrenergic mechanisms regulate human sympathetic neuronal discharge strategies"],"prefix":"10.1113","volume":"602","author":[{"given":"Stephen A.","family":"Klassen","sequence":"first","affiliation":[{"name":"Sympathetic Neurocirculatory Regulation Laboratory Department of Kinesiology Brock University  St Catharines ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline K.","family":"Limberg","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Exercise Physiology University of Missouri  Columbia MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron\u00e9e E.","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad C.","family":"Wiggins","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Michigan State University  East Lansing MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel J.","family":"Iannarelli","sequence":"additional","affiliation":[{"name":"Sympathetic Neurocirculatory Regulation Laboratory Department of Kinesiology Brock University  St Catharines ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathon W.","family":"Senefeld","sequence":"additional","affiliation":[{"name":"Department of Health and Kinesiology, Beckman Institute for Advanced Science and Technology, University of Illinois Urbana\u2010Champaign University of Illinois at Urbana\u2010Champaign  Champaign IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne T.","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B.","family":"Curry","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Joyner","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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