Nicotine increases initial blood flow responses to local heating of human non‐glabrous skin

Abstract

Nicotine affects the regulation of skin blood flow (SkBF), but the mechanisms involved are not well understood. We tested the hypothesis that acute exposure to nicotine inhibits both the initial neurally mediated component and the later sustained component of SkBF responses to local heating of non-glabrous skin in humans. SkBF (measured by laser-Doppler) responses to local heating of forearm skin from 32 to 42• C were measured in 11 chronic smokers. Heating occurred at one site over 15 min (RAMP) and over 90 s (STEP) at another site, and was maintained for an additional 30 min. STEP heating was also applied to a site pretreated with bretylium via iontophoresis to inhibit noradrenergic neurotransmission. Responses were measured before and after acute administration of nicotine via cigarettes or nasal spray in two experimental sessions. Nicotine decreased resting skin blood flow (P < 0.05); this response was inhibited by bretylium. During RAMP, nicotine increased the initial SkBF at 42• C (by ∼12%, P < 0.05). For STEP, nicotine increased the initial peak response (by ∼25%, P < 0.05), and decreased the sustained plateau value (by ∼10%, P < 0.05). In skin pretreated with bretylium, the increase caused by nicotine in the initial peak value persisted, but the plateau value was not different from pre-nicotine. These data suggest that in abstinent cigarette smokers, nicotine augments initial responses to both gradual and rapid non-painful heating of non-glabrous skin by sensitizing the sensory nerves that mediate the axon reflex associated with rapid vasodilatation. In contrast, nicotine decreases SkBF responses to prolonged heating by activating noradrenergic nerves.

Forearm cutaneous vascular and sudomotor responses to whole body passive heat stress in young smokers

“…This was contrary to our hypothesis that smokers would have attenuated CVC responses during whole body heat stress because of the reported endothelial damage and decreased endothelial nitric oxide synthase production (24,34). The similar CVC sensitivity between groups is likely a result of using whole body heat stress to elicit increases in reflex vasodilation (CVC), compared with previous literature that used local stimuli [e.g., iontophoresis (10,14,19), microdialysis (15), and local heating (43)] to invoke postsynaptic increases in CVC. Prior research (10,14,15,19,43) showing that smokers have impaired maximal skin blood flow isolated postsynaptic activity, which is typically indicative of eNOS-dependent vasodilation (21).…”

“…The similar CVC sensitivity between groups is likely a result of using whole body heat stress to elicit increases in reflex vasodilation (CVC), compared with previous literature that used local stimuli [e.g., iontophoresis (10,14,19), microdialysis (15), and local heating (43)] to invoke postsynaptic increases in CVC. Prior research (10,14,15,19,43) showing that smokers have impaired maximal skin blood flow isolated postsynaptic activity, which is typically indicative of eNOS-dependent vasodilation (21). However, cutaneous vasodilation that occurs during whole body heat stress is an integration of presynaptic and postsynaptic activity, and is largely reliant on eNOS-independent pathways (21,22).…”

“…1). It is unknown what mechanism(s) caused the earlier onset for cutaneous vasodilation in SMK; however, it could be that similar to sweating, vasodilation was initiated by the combination of whole body heat stress and nicotine (43). More mechanistic studies are required to determine the exact pathways mediating these responses.…”

“…Although we are unaware of any studies examining vasodilation during whole body heating in smokers, several studies show smokers have impairments to local stimuli [e.g., iontophoresis (10,14,19), microdialysis (15), and local heating (43)]. Smokers have impaired postsynaptic endothelial nitric oxide synthase (eNOS)-dependent and eNOS-independent maximal vasodilation (1,10,14,15,19,28,43).…”

Using multifractal detrended fluctuation analysis to assess sacral skin blood flow oscillations in people with spinal cord injury

“…Warner et al showed that nicotine caused a decrease in resting and maximal skin blood flow responses to prolonged heating [44]. Argacha et al demonstrated that passive smoking was associated with a prolonged rise of skin blood flow in response to local heating [45].…”