Microvascular Responses to Common Endothelial Stimuli Are Not Related in Humans
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Background
Cutaneous microvascular responses to local heating and acetylcholine perfusion are widely used to assess nitric oxide (NO)-mediated endothelium-dependent dilation in human health and disease. Despite the increasingly common usage of these approaches, no studies have directly compared responses to these stimuli within individuals. Therefore, we assessed endothelium- and NO-dependent dilation in 80 young adults (40 males/40 females; 22±3 years) to determine the extent to which microvascular responses to these endothelium-dependent stimuli are comparable within an individual.
Methods
We examined cutaneous vascular conductance responses to (1) standardized local heating protocols to 39°C and 42°C, and (2) graded infusions of acetylcholine (10 -10 -10 -1 M) alone or with 15 mM N G -nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor). Endothelium- and NO-dependent dilation were calculated and expressed in multiple ways based on commonly published analyses to allow for a thorough comparison within and between each stimulus.
Results
Local heating-induced endothelium- and NO-dependent dilation were lower at 39°C compared with 42°C (P<0.001). The magnitude of local heating-induced endothelium-dependent dilation was significantly related to the NO-dependent contribution of that response at 39°C (R 2 = 0.79) and 42°C (R 2 = 0.56). Local heating-induced NO-dependent dilation at 39°C was not related to that at 42°C (P>0.05). Acetylcholine-induced endothelium- and NO-dependent dilation were not related to local heating-induced responses (all P>0.05).
Conclusions
These data demonstrate that while local heating and acetylcholine perfusion produce robust endothelium- and NO-dependent cutaneous vasodilation, these responses are not comparable within an individual.
Clinical Trial Registration
URL: https://www.clinicaltrials.gov/ Unique identifier: NCT06499844
Novelty and Relevance
What Is New?
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Local thermal heating and acetylcholine perfusion each produce robust endothelium- and nitric oxide-dependent cutaneous vasodilation. However, these responses are not directly comparable within an individual.
What Is Relevant?
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Changes in microvascular function precede and predict adverse changes in conduit vessels and are reversible before the onset of overt vascular disease and target organ damage.
Clinical/Pathophysiological Implications?
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These approaches are widely used by investigators to interrogate mechanisms of microvascular function and dysfunction in humans. Selection of the appropriate approach should be based on the specific research question and pathophysiological mechanism under investigation.
