title: Neurovascular mechanisms underlying augmented cold-induced reflex cutaneous vasoconstriction in human hypertension.
abstract: In hypertensive adults (HTN), cardiovascular risk increases disproportionately during environmental cold exposure. 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. The findings of the present study show that whole-body cold stress elicits greater increases in sympathetic outflow directed to the cutaneous vasculature and, correspondingly, greater reductions in skin blood flow in HTN. We further demonstrate an important role for non-adrenergic sympathetic co-transmitters in mediating the vasoconstrictor response to cold stress in hypertension. In the context of thermoregulation and the maintenance of core temperature, sympathetically-mediated 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-induced alterations in neurovascular function during cold exposure is clinically relevant.
  
  
  
  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-body cooling would elicit greater cutaneous vasoconstriction and greater increases in skin sympathetic nervous system activity (SSNA) in HTN (n = 14; 56 ± 2 years) compared to age-matched normotensive adults (NTN; n = 14; 55 ± 2 years) and (ii) augmented reflex vasoconstriction in HTN would be mediated by an increase in cutaneous vascular adrenergic sensitivity and a greater contribution of non-adrenergic sympathetic co-transmitters. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry; dorsum of foot) were measured during whole-body cooling (water-perfused suit). Sympathetic adrenergic- and non-adrenergic-dependent contributions to reflex cutaneous vasoconstriction and vascular adrenergic sensitivity were assessed pharmacologically using intradermal microdialysis. Cooling elicited greater increases in SSNA (NTN: +64 ± 13%baselinevs. HTN: +194 ± 26%baseline; P < 0.01) and greater reductions in skin blood flow (NTN: -16 ± 2%baselinevs. HTN: -28 ± 3%baseline; P < 0.01) in HTN compared to NTN, reflecting an increased response range for sympathetic reflex control of cutaneous vasoconstriction in HTN. Norepinephrine dose-response curves showed no HTN-related difference in cutaneous adrenergic sensitivity (logEC50; NTN: -7.4 ± 0.3 log M vs. HTN: -7.5 ± 0.3 log M; P = 0.84); however, non-adrenergic sympathetic co-transmitters 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-adrenergic neurotransmitters.
authors.affiliation: Department of Kinesiology, Noll Laboratory, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Jody L
authors.identifier: 0000-0002-9855-3978
authors.initials: JL
authors.lastname: Greaney
authors.affiliation: Department of Kinesiology, Noll Laboratory, The Pennsylvania State University, University Park, PA, USA.
authors.forename: W Larry
authors.initials: WL
authors.lastname: Kenney
authors.affiliation: Department of Kinesiology, Noll Laboratory, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Lacy M
authors.initials: LM
authors.lastname: Alexander
mesh_terms: D003080:Cold Temperature; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010543:Peroneal Nerve / Q000502:physiology; D012018:Reflex / Q000502:physiology; D012867:Skin / Q000098:blood supply / Q000294:innervation; D012879:Skin Physiological Phenomena; D013564:Sympathetic Nervous System / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
keywords: cold stress; skin blood flow; sympathetic nerve activity; vascular sensitivity