Going With The (blood) Flow: Assessing Skeletal Muscle Microvascular Function In Middle-aged Adults

Microvascular endothelial dysfunction is a feature of cardiovascular (CV) aging and precedes CV disease (CVD) onset, elevating risk for ischemic stroke and broader peripheral vascular dysfunction. Coincident vasodilatory decrements in skeletal muscle, an important site of peripheral resistance, may compound CVD risk. Alongside traditional CV health and fitness markers, assessments of the muscle microvasculature during the onset of age-related vascular changes are needed. PURPOSE: To assess microvascular function by testing the endothelium-dependent vasodilatory response in resting skeletal muscle, considering age, mean arterial pressure (MAP), and cardiorespiratory fitness (V̇O2peak). METHODS: Microvascular blood flow (MBF) was examined in the vastus lateralis of five males (age, yrs: 53 ± 1.6, BMI: 25 - 30 kg/m2, V̇O2peak: 54 ± 3.2) using microdialysis. Two microdialysis probes were perfused with a control saline solution containing 5 mM ethanol (CTRL) in the presence or absence of 50 mM acetylcholine (ACh; endothelium-dependent vasodilator) at alternate timepoints. MBF was expressed as the ethanol outflow-to-inflow ratio (O:I), which is inversely related to blood flow, and was log transformed for statistical analysis utilizing a Bayesian multilevel approach. RESULTS: There were small independent effects of age (β: 0.11, 95% CrI [-0.21, 0.39] pd = 82%), MAP (β: 0.02, 95% CrI [-0.03, 0.06] pd = 83%) and V̇O2peak (β: -0.01, 95% CrI [-0.11, 0.09] pd = 57%) on loge O:I. Estimated marginal means and their contrasts suggest minimal difference in loge O:I compared to CTRL (0.06 ± 0.07, pd = 82%), with ACh perfusion corresponding to a decrease in MBF by approximately 6%. CONCLUSIONS: Compared to CTRL, MBF decreased in the presence of ACh, which may suggest negative perturbations in endothelium-dependent vasodilatory function in this overweight but apparently healthy cohort. However, in this preliminary stage there is weak evidence to claim any clinical relevance. Further investigation into possible substance- and time-dependent vasodilatory effects are needed. Future research will require a larger sample size and wider range of ages to deduce any age-related effects, which could inform novel CVD screening or intervention strategies.