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Cholinergic nerve contribution to cutaneous active vasodilation in response to exercise heat‐loading is similar to passive whole‐body heat‐loading

Twenty‐five years ago, Dean Kellogg and colleagues established the sympathetic cholinergic nerve co‐transmitter theory for cutaneous active vasodilation (CAVD) during passive heating in humans. In this seminal study, pretreatment of the skin with botulinum toxin type‐A (BOTOX), a presynaptic cholinergic nerve blocker, abolished CAVD during passive whole‐body heat stress in six subjects. To date, these findings have not been confirmed. More recently, a clear role for NO in CAVD has been established, where NO accounts for up to 50% of CAVD. The specific isoform of NO‐synthase has been reported to differ between CAVD in response to different thermal loading modalities (passive heating vs. exercise). These findings suggest that there may be mechanistic differences in the skin blood flow responses (SkBF) to hyperthermic challenge that are dependent on how thermal loading is accomplished. With this in mind, it is unknown if the cholinergic co‐transmitter theory of CAVD applies to other thermal loading modalities such as exercise heat‐loading. Therefore, this study sought to confirm the role of cholinergic nerve activation in CAVD during passive whole‐body heat‐loading and expand these findings to exercise heat‐loading using a cross‐over study design. It was hypothesized that CAVD during exercise and passive whole‐body heating would both be abolished by BOTOX administration.