{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T21:05:17Z","timestamp":1765487117668,"version":"3.41.2"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,8,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric\u2010oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin\u2010mediated vasodilation in adult subjects with obesity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast\u2010enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21\u00b11.22 to 4.89\u00b14.21\u2009mL\/100\u2009mL\u2009per\u2009min,\n              <jats:italic>P<\/jats:italic>\n              =0.003 and from 2.42\u00b10.89 to 7.19\u00b13.35\u2009mL\/100\u2009mL\u2009per\u2009min,\n              <jats:italic>P<\/jats:italic>\n              =0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (\u2206microvascular flow velocity: 0.23\u00b10.65 versus 2.51\u00b13.01 arbitrary intensity units (AIU\/s) for saline and phentolamine respectively,\n              <jats:italic>P<\/jats:italic>\n              =0.005), microvascular blood volume (\u2206microvascular blood volume: 1.69\u00b12.45 versus 3.76\u00b12.93\u2009AIU, respectively,\n              <jats:italic>P<\/jats:italic>\n              =0.05), and microvascular blood flow (\u2206microvascular blood flow: 0.28\u00b10.653 versus 2.51\u00b13.01\u2009AIU\n              <jats:sup>2<\/jats:sup>\n              \/s, respectively,\n              <jats:italic>P<\/jats:italic>\n              =0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin\u2010induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively,\n              <jats:italic>P<\/jats:italic>\n              =0.031).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">We conclude that sympathetic activation impairs insulin\u2010mediated microvascular recruitment in adult subjects with obesity.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.030775","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T11:31:58Z","timestamp":1723203118000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Acute Sympathetic Blockade Improves Insulin\u2010Mediated Microvascular Blood Flow in the Forearm of Adult Human Subjects With Obesity"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5078-6748","authenticated-orcid":false,"given":"Emily C.","family":"Smith","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9148-2778","authenticated-orcid":false,"given":"Jay N.","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Cardiology Vanderbilt University Medical Center Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amr","family":"Wahba","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Cluckey","sequence":"additional","affiliation":[{"name":"Division of Cardiology Vanderbilt University Medical Center Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Celedonio","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5548-3378","authenticated-orcid":false,"given":"JinWoo","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1676-1096","authenticated-orcid":false,"given":"LaToya","family":"Hannah","sequence":"additional","affiliation":[{"name":"Human Metabolic Physiology Core Vanderbilt University Medical Center Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanna","family":"Lonce","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4518-6801","authenticated-orcid":false,"given":"Cyndya A.","family":"Shibao","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4597-9705","authenticated-orcid":false,"given":"Sachin Y.","family":"Paranjape","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5643-0294","authenticated-orcid":false,"given":"Andre","family":"Diedrich","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1778-3203","authenticated-orcid":false,"given":"Owen","family":"McGuinness","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7667-7083","authenticated-orcid":false,"given":"Italo","family":"Biaggioni","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN"},{"name":"Department of Pharmacology Vanderbilt University Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8676-687X","authenticated-orcid":false,"given":"Alfredo","family":"Gamboa","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville 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