New Findings What is the topic of this review?This review presents an update and synthesis of normal mechanisms of human cutaneous vasoconstriction in response to cold stress. It then discusses conditions in which cutaneous vasoconstrictor responses are excessive or insufficient and cases in which cold‐induced vasoconstrictor responses become counter to maintaining thermal and haemodynamic homeostasis. What advances does it highlight?The review highlights our current understanding of the mechanisms that mediate alterations in cold‐induced cutaneous vasoconstriction in pathology and environmental extremes, which has important clinical implications for preventing cold‐ and cardiovascular‐related deaths. Abstract In humans, cold‐induced peripheral vasoconstriction is an essential element of body temperature regulation. Given that the thermoregulatory system responds rapidly to changes in skin temperature, sympathetically mediated cutaneous vasoconstriction represents a crucial ‘first line of defense’ against excessive reduction in body temperature. Sympathetic noradrenergic vasoconstrictor nerves cause a rapid decrease in skin blood flow, thus increasing the insulative capacity of the skin and decreasing heat loss from the body. Small changes in the activity of these nerves are also responsible for the subtle changes in skin blood flow that occur with normal daily activities or minor changes in environmental temperature. With ageing, hypertension and other conditions, the cutaneous reflex vasoconstrictor response can become excessive or insufficient. Healthy older adults have impaired reflex vasoconstriction, which may result in an impaired ability to defend body temperature in some circumstances. Hypertension is associated with augmented vasoconstriction, which could have pathological implications for left ventricular afterload in individuals already at risk for cardiovascular events. Finally, in some cases, the reflex vasoconstrictor response becomes distinctly counterproductive to its own goals of maintaining cardiovascular and thermoregulatory homeostasis. Examples include Raynaud's phenomenon, in which exaggerated vasoconstriction can produce ischaemia in the periphery, and the cutaneous vasoconstrictor response to therapeutic body cooling in severe hyperthermia, which can limit the heat exchange necessary to prevent serious heat illness.

Psoriasis is an independent risk factor for cardiovascular disease; however, the underlying mechanisms are not fully understood. Deficits in conduit arterial function are evident in patients with psoriasis, but potential impairments in microcirculatory endothelial function remain unclear. We hypothesized that cutaneous microvascular dysfunction would be detectable in otherwise healthy individuals with psoriasis. Two intradermal microdialysis fibers were placed in (nonlesional) forearm skin of nine patients (3 men and 6 women, 39 ± 5 yr) with moderate (16 ± 2% of body surface area) plaque psoriasis and nine healthy (nonpsoriatic) control subjects (3 men and 6 women, 38 ± 5 yr) for local delivery of 1) lactated Ringer solution (control) and 2) 10 mM l-ascorbate (a nonspecific antioxidant). An index of skin blood flow was measured using laser-Doppler flowmetry during local heating (42°C). Nitric oxide (NO)-dependent vasodilation was directly quantified after perfusion of the nonspecific NO synthase inhibitor N-nitro-l-arginine methyl ester (15 mM). A third fiber was perfused with increasing concentrations (10 - 10 M) of norepinephrine to elicit adrenoreceptor-mediated cutaneous vasoconstriction. NO-dependent vasodilation was attenuated in patients with psoriasis (57 ± 5% and 39 ± 7% maximum cutaneous vascular conductance in control subjects and adults with psoriasis, respectively, P < 0.01). l-Ascorbate did not improve NO-dependent vasodilation ( P > 0.05). There was no group difference in maximal vasoconstriction or microvascular sensitivity to norepinephrine ( P > 0.05). These data suggest that NO bioavailability is reduced in otherwise healthy individuals with psoriasis, which contributes to systemic microvascular dysfunction. NEW & NOTEWORTHY In adults with psoriasis, reduced nitric oxide bioavailability mediates impaired endothelium-dependent vasodilation, independent of increases in oxidative stress. Furthermore, the degree of psoriatic symptomology is directly related to greater reductions in nitric oxide-dependent vasodilation.

Habituation is an adaptation seen in many organisms, defined by a reduction in the response to repeated stimuli. Evolutionarily, habituation is thought to benefit the organism by allowing conservation of metabolic resources otherwise spent on sub-lethal provocations including repeated cold exposure. Hypermetabolic and/or insulative adaptations may occur after prolonged and severe cold exposures, resulting in enhanced cold defense mechanisms such as increased thermogenesis and peripheral vasoconstriction, respectively. Habituation occurs prior to these adaptations in response to short duration mild cold exposures, and, perhaps counterintuitively, elicits a reduction in cold defense mechanisms demonstrated through higher skin temperatures, attenuated shivering, and reduced cold sensations. These habituated responses likely serve to preserve peripheral tissue temperature and conserve energy during non-life threatening cold stress. The purpose of this review is to define habituation in general terms, present evidence for the response in non-human species, and provide an up-to-date, critical examination of past studies and the potential physiological mechanisms underlying human cold habituation. Our aim is to stimulate interest in this area of study and promote further experiments to understand this physiological adaptation.

In epidemiological studies, chronic dairy consumption is associated with improved vascular health and reduced age-related increases in blood pressure. While milk protein supplementation augments conduit artery flow-mediated dilation, whether or not acute dairy milk intake may improve microvascular function remains unclear. We hypothesized that dairy milk would increase direct measurement of endothelial nitric oxide (NO)-dependent cutaneous vasodilation in response to local skin heating. Eleven men and women (61±2 years) ingested 2 or 4 servings (473 mL and 946 mL) of 1% dairy milk or a rice beverage on each of four separate study days. In a subset of five subjects an additional protocol was completed after 473 mL of water ingestion. Once a stable blood flow occurred, 15 mM L-NAME was perfused (intradermal microdialysis) to quantify NO-dependent vasodilation. Red blood cell flux (RBF) was measured by laser-Doppler flowmetry (LDF) and cutaneous vascular conductance (CVC=RBF/MAP) was calculated and normalized to maximum (%CVCmax; 28 mM SNP). Full expression of cutaneous vasodilation was not different among dairy milk, rice beverage and water and there was no effect of serving size on the total vasodilatory response. Contrary to our hypothesis, NO-dependent vasodilation was lower for dairy milk than rice beverage (D: 49±5, R: 55±5 %CVCmax; p<0.01). Acute dairy milk ingestion does not augment NO-dependent vasodilation in the cutaneous microcirculation compared to a rice beverage control.