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In the present study, we aimed to determine whether GABA<jats:sub>A<\/jats:sub> receptors modulate the neurocardiovascular responses to activation of metabolically sensitive (predominantly mediated by group IV fibres) skeletal muscle afferents in humans. In a randomized, double\u2010blinded, placebo\u2010controlled and cross\u2010over design, 17 healthy subjects (eight women) performed 2\u00a0min of ischaemic isometric handgrip exercise at 30% of the maximal voluntary contraction followed by 2\u00a0min of postexercise ischaemia (PEI). Muscle sympathetic nerve activity (MSNA), blood pressure (BP) and heart rate (HR) were continuously measured and trials were conducted before and 60\u00a0min after the oral administration of either placebo or diazepam (10\u00a0mg), a benzodiazepine that enhances GABA<jats:sub>A<\/jats:sub> activity. At rest, MSNA was reduced, whereas HR and BP did not change after diazepam administration. During ischaemic isometric handgrip, greater MSNA (pre: \u220613\u00a0\u00b1\u00a09\u00a0bursts\u00a0min<jats:sup>\u22121<\/jats:sup> <jats:italic>vs<\/jats:italic>. post: \u220629\u00a0\u00b1\u00a015\u00a0bursts\u00a0min<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), HR (pre: \u220623\u00a0\u00b1\u00a011\u00a0beats\u00a0min<jats:sup>\u22121<\/jats:sup> <jats:italic>vs<\/jats:italic>. post: \u220631\u00a0\u00b1\u00a017\u00a0beats\u00a0min<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and mean BP (pre: \u220633\u00a0\u00b1\u00a012\u00a0mmHg <jats:italic>vs<\/jats:italic>. post: \u220637\u00a0\u00b1\u00a012\u00a0mmHg, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) responses were observed after diazepam. During PEI, MSNA and mean BP remained elevated from baseline before diazepam (\u220610\u00a0\u00b1\u00a08\u00a0bursts\u00a0min<jats:sup>\u22121<\/jats:sup> and \u220625\u00a0\u00b1\u00a014\u00a0mmHg, respectively) and these elevations were increased after diazepam (\u220617\u00a0\u00b1\u00a012\u00a0bursts\u00a0min<jats:sup>\u22121<\/jats:sup> and \u220628\u00a0\u00b1\u00a013\u00a0mmHg, respectively) (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.05). Importantly, placebo pill had no effect on neural, cardiac and pressor responses. These findings demonstrate for the first time that GABA<jats:sub>A<\/jats:sub> receptors modulate MSNA and the pressor responses to skeletal muscle metaboreflex activation in humans.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp277929","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T21:24:31Z","timestamp":1561670671000},"page":"4139-4150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["GABA<sub>A<\/sub> receptors modulate sympathetic vasomotor outflow and the pressor response to skeletal muscle metaboreflex activation in humans"],"prefix":"10.1113","volume":"597","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4268-7560","authenticated-orcid":false,"given":"Andr\u00e9 L.","family":"Teixeira","sequence":"first","affiliation":[{"name":"NeuroV\u0307ASQ\u0307\u00a0\u2013\u00a0Integrative Physiology Laboratory Faculty of Physical Education University of Bras\u00edlia  Bras\u00edlia 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