Neurovascular mechanisms underlying augmented cold-induced reflex cutaneous vasoconstriction in human hypertension.

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%baseline  vs. HTN: +194 ± 26%baseline ; P < 0.01) and greater reductions in skin blood flow (NTN: -16 ± 2%baseline  vs. 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.