Supplementary Material for: REGULATION OF SKELETAL MUSCLE RESISTANCE ARTERIOLAR TONE: TEMPORAL VARIABILITY IN VASCULAR RESPONSES

Introduction: A full understanding of the integration of the mechanisms of vascular tone regulation requires an interrogation of the temporal behavior of arterioles across vasoactive challenges. Building on previous work, the purpose of the present study is to start to interrogate the temporal nature of arteriolar tone regulation with physiological stimuli. Methods: We determined the response rate of ex vivo proximal and in situ distal resistance arterioles when challenged by one-, two-and three-parameter combinations of five major physiological stimuli (norepinephrine, intravascular pressure, oxygen, adenosine (metabolism) and intralumenal flow). Predictive machine learning models determined which factors were most influential in controlling the rate of arteriolar responses. Results: Results indicate that vascular response rate is dependent on the intensity of the stimulus used and can be severely hindered by altered environments, caused by application of secondary or tertiary stimuli. Advanced analytics suggest that adrenergic influences were dominant in predicting proximal arteriolar response rate compared to metabolic influences in distal arterioles. Conclusion: These data suggest that the vascular response rate to physiologic stimuli can be strongly influenced by the local environment. Translating how these effects impact vascular networks is imperative for understanding how the microcirculation appropriately perfuses tissue across conditions.