{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:03:27Z","timestamp":1790809407035,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T00:00:00Z","timestamp":1484524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL093238"],"award-info":[{"award-number":["HL093238"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F32 HL120471"],"award-info":[{"award-number":["F32 HL120471"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>In hypertensive adults (HTN), cardiovascular risk increases disproportionately during environmental cold exposure.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Despite ample evidence of dysregulated sympathetic control of the peripheral vasculature in hypertension, no studies have examined integrated neurovascular function during cold stress in HTN.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The findings of the present study show that whole\u2010body cold stress elicits greater increases in sympathetic outflow directed to the cutaneous vasculature and, correspondingly, greater reductions in skin blood flow in HTN.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>We further demonstrate an important role for non\u2010adrenergic sympathetic co\u2010transmitters in mediating the vasoconstrictor response to cold stress in hypertension.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In the context of thermoregulation and the maintenance of core temperature, sympathetically\u2010mediated control of the cutaneous vasculature is not only preserved, but also exaggerated in hypertension. Given the increasing prevalence of hypertension, clarifying the mechanistic underpinnings of hypertension\u2010induced alterations in neurovascular function during cold exposure is clinically relevant.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Despite ample evidence of dysregulated sympathetic control of the peripheral vasculature in hypertension, no studies have examined integrated neurovascular function during cold stress in hypertensive adults (HTN). We hypothesized that (i) whole\u2010body cooling would elicit greater cutaneous vasoconstriction and greater increases in skin sympathetic nervous system activity (SSNA) in HTN (<jats:italic>n<\/jats:italic>\u00a0=\u00a014; 56\u00a0\u00b1\u00a02\u00a0years) compared to age\u2010matched normotensive adults (NTN;<jats:italic>n<\/jats:italic>\u00a0=\u00a014; 55\u00a0\u00b1\u00a02\u00a0years) and (ii) augmented reflex vasoconstriction in HTN would be mediated by an increase in cutaneous vascular adrenergic sensitivity and a greater contribution of non\u2010adrenergic sympathetic co\u2010transmitters. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry; dorsum of foot) were measured during whole\u2010body cooling (water\u2010perfused suit). Sympathetic adrenergic\u2010 and non\u2010adrenergic\u2010dependent contributions to reflex cutaneous vasoconstriction and vascular adrenergic sensitivity were assessed pharmacologically using intradermal microdialysis. Cooling elicited greater increases in SSNA (NTN: +64\u00a0\u00b1\u00a013%<jats:sub>baseline<\/jats:sub>\u00a0<jats:italic>vs<\/jats:italic>. HTN: +194\u00a0\u00b1\u00a026%<jats:sub>baseline<\/jats:sub>;<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and greater reductions in skin blood flow (NTN: \u221216\u00a0\u00b1\u00a02%<jats:sub>baseline<\/jats:sub>\u00a0<jats:italic>vs<\/jats:italic>. HTN: \u221228\u00a0\u00b1\u00a03%<jats:sub>baseline<\/jats:sub>;<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) in HTN compared to NTN, reflecting an increased response range for sympathetic reflex control of cutaneous vasoconstriction in HTN. Norepinephrine dose\u2013response curves showed no HTN\u2010related difference in cutaneous adrenergic sensitivity (logEC<jats:sub>50<\/jats:sub>; NTN: \u22127.4\u00a0\u00b1\u00a00.3\u00a0log M\u00a0<jats:italic>vs<\/jats:italic>. HTN: \u22127.5\u00a0\u00b1\u00a00.3\u00a0log M;<jats:italic>P<\/jats:italic>\u00a0=\u00a00.84); however, non\u2010adrenergic sympathetic co\u2010transmitters mediated a significant portion of the vasoconstrictor response to cold stress in HTN. Collectively, these findings indicate that hypertension increases the peripheral cutaneous vasoconstrictor response to cold via greater increases in skin sympathetic outflow coupled with an increased reliance on non\u2010adrenergic neurotransmitters.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp273487","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T09:56:50Z","timestamp":1480327010000},"page":"1687-1698","source":"Crossref","is-referenced-by-count":43,"title":["Neurovascular mechanisms underlying augmented cold\u2010induced reflex cutaneous vasoconstriction in human hypertension"],"prefix":"10.1113","volume":"595","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9855-3978","authenticated-orcid":false,"given":"Jody L.","family":"Greaney","sequence":"first","affiliation":[{"name":"Department of Kinesiology, Noll Laboratory The Pennsylvania State University University Park PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Larry","family":"Kenney","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, Noll Laboratory The Pennsylvania State University University Park PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lacy M.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, Noll Laboratory The Pennsylvania State University University Park PA 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