Evidence regarding the impact of menstrual phase on endothelial function is conflicting, and studies to date have examined responses only over a single cycle.It is unknown whether the observed inter-individual variability of phase changes in endothelial function reflects stable, inter-individual differences in responses to oestrogen (E 2 ; a primary female sex hormone). The purpose of this study was to examine changes in endothelial function from the early follicular (EF; low-E 2 ) phase to the late follicular (LF; high-E 2 ) phase over two consecutive cycles. Fourteen healthy, regularly menstruating women [22 ± 3 years of age (mean ± SD)] participated in four visits (EF Visit 1 , LF Visit 2 , EF Visit 3 and LF Visit 4 ) over two cycles. Ovulation testing was used to determine the time between the LF visit and ovulation. During each visit, endothelial function [brachial artery flow-mediated dilatation (FMD)], E 2 and progesterone were assessed. At the group level, there was no impact of phase or cycle on FMD (P = 0.48 and P = 0.65, respectively). The phase change in FMD in cycle 1 did not predict the phase change in cycle 2 (r = 0.03, P = 0.92). Using threshold-based classification (2 × typical error threshold), four of 14 participants (29%) exhibited directionally consistent phase changes in FMD across cycles. Oestrogen was not correlated between cycles, and this might have contributed to variability in the FMD response. The intra-individual variability in follicular fluctuation in FMD between menstrual cycles challenges the utility of interpreting individual responses to phase over a single menstrual cycle.

Passive leg movement-elicited hyperaemia (PLM-H) provides an index of lower-limb microvascular function. However, there is currently limited information regarding the reliability of PLM-H and no reliability information specific to women. The purpose of this study was to determine the reliability of PLM-H in women on two separate days. Seventeen young, healthy women [22 ± 3 years old (mean ± SD)] participated in two identical visits including three trials of PLM. Using duplex ultrasound, PLM-H was characterized by six indices: peak leg blood flow (LBF) and vascular conductance (LVC), peak change above baseline (Δpeak) for LBF and LVC, and area under the curve above baseline (AUC) during the first 60 s of PLM for LBF and LVC. The results demonstrated good day-to-day reliability of PLM-H characterized as peak LBF [r = 0.84, P < 0.001; intraclass correlation coefficient (ICC) = 0.84; coefficient of variation (CV) = 13.2%],

The objective of this study was to examine the impact of a shame induction protocol on endothelial function. Fifteen participants (n = 7 men, n = 8 women) completed both a written shame induction protocol and a control protocol on two different experimental days. Pre-and post-protocol we assessed: (1) endothelial function and arterial shear rate via a standard brachial artery reactive hyperaemia flow-mediated dilatation (FMD) test across two post-intervention time points (15 and 35 min post); (2) perceived shame via the experiential shame scale (ESS); and (3) cortisol and soluble tumor necrosis factor alpha receptor (sTNFαRII) through oral fluid analysis. Shame increased after the shame induction protocol (pre, 2.9 ± 0.6 vs. post, 3.7 ± 0.5, P < 0.001) but not the control protocol (pre, 3.0 ± 0.5 vs. post, 2.8 ± 0.5, P = 0.15; protocol by time interaction, P < 0.001). When all three time points were included in the analysis, %FMD did not change over time. Considering only the lowest post time point, %FMD decreased significantly in response to the shame protocol (pre, 4.8 ± 1.9 vs. post, 3.2 ± 1.6, P < 0.001) but not the control protocol (pre, 4.2 ± 1.8 vs. post, 3.8 ± 1.5, P = 0.45; protocol by time interaction, P = 0.035). Covariation of the shear rate stimulus for FMD did not alter the FMD results. When including both the control and shame protocols, but not the shame protocol alone, increased shame was significantly associated with decreased FMD (r = −0.37, P < 0.046). There were no significant time by protocol interaction effects for cortisol or sTNFαRII. In conclusion, temporary increases in shame might cause transient endothelial dysfunction which, if chronically repeated, could manifest as reduced vasoprotection against atherosclerosis.

In electrically stimulated skeletal muscle, force production is downregulated when oxygen delivery is compromised and rapidly restored upon restoration of oxygen delivery in the absence of cellular disturbance. Whether this 'oxygen-conforming' response of force occurs and is exercise intensity dependent during stable voluntary muscle activation in humans is unknown. In 12 participants (six female), handgrip force, forearm muscle activation (EMG), muscle oxygenation and forearm blood flow (FBF)were measured during rhythmic handgrip exercise at forearm EMG achieving 50, 75 or 90% critical impulse (CI). Four minutes of brachial artery compression to reduce FBF by ∼60% (Hypoperfusion) or sham compression (adjacent to artery; Control) was performed during exercise. Sham compression had no effect. Hypoperfusion rapidly reduced muscle oxygenation at all exercise intensities, resulting in contraction force per muscle activation (force/EMG) progressively declining over 4 min by ∼16% at both 75 and 90% CI. No force/EMG decline occurred at 50% CI. Rapid restoration of muscle oxygenation after compression was closely followed by force/EMG such that it was not different from Control within 30 s for 90% CI and after 90 s for 75% CI. Our findings reveal that an oxygen-conforming response does occur in voluntary exercising muscle in humans. Within the exercise modality and magnitude of fluctuation of oxygenation in this study, the oxygen-conforming response appears to be exercise intensity dependent. Mechanisms responsible for this oxygen-conforming response have implications for exercise tolerance and warrant investigation.

Oxygen delivery is viewed as tightly coupled to demand in exercise below critical power because increasing oxygen delivery does not increase VO2${V_{{O_2}}}$. However, whether the ‘normal’ adjustment of oxygen delivery to small muscle mass exercise in the heavy intensity domain is optimal for excitation–contraction coupling is currently unknown. In 20 participants (10 female), a remote skeletal muscle (i.e. tibialis anterior) metaboreflex was (Hyperperfusion condition) or was not (Control condition) activated for 4 min during both force of contraction (experimental model 1) and muscle activation‐targeted (experimental model 2) rhythmic forearm handgrip exercise. Analysis was completed on the combined data from both experimental models. After 30 s of remote skeletal muscle metaboreflex activation, mean arterial blood pressure, forearm blood flow and muscle oxygenation were increased and remained increased until metaboreflex discontinuation. While oxygen delivery was elevated, the muscle activation to force of contraction ratio was improved. Upon metaboreflex discontinuation, forearm oxygen delivery and the muscle activation and force of contraction ratio rapidly (within 30 s) returned to control levels. These findings demonstrate that (a) the metaboreflex was effective at increasing forearm muscle oxygen delivery and oxygenation, (b) the muscle activation to force of contraction ratio was improved with increased oxygen delivery, and (c) in the heavy exercise intensity domain, the normal matching of oxygen delivery to metabolic demand is not optimal for muscle excitation–contraction coupling. These results suggest that the nature of vasoregulation in exercising muscle is such that it does not support optimal perfusion for excitation–contraction coupling. Key points Oxygen delivery is viewed as tightly coupled to demand in exercise below critical power because increasing oxygen delivery does not increase the rate of oxygen uptake. Whether the ‘normal’ adjustment of oxygen delivery in small muscle mass exercise below critical power is optimal for excitation–contraction coupling is not known. Here we show in humans that increasing oxygen delivery above ‘normal’ improves excitation–contraction coupling. These results suggest that, in the heavy exercise intensity domain, the ‘normal’ matching of oxygen delivery to metabolic demand is not optimal for muscle excitation–contraction coupling. Therefore, the nature of vasoregulation in exercising muscle is such that it does not support optimal perfusion for excitation–contraction coupling.

BackgroundTo combat historical underrepresentation of female participants in research, guidelines have been established to motivate equal participation by both sexes. However, the pervasiveness of female exclusion has not been examined in vascular exercise physiology research. The purpose of this study was to systematically quantify the sex-specific prevalence of human participants and identify the rationales for sex-specific inclusion/exclusion in research examining the impact of exercise on vascular endothelial function.MethodsA systematic search was conducted examining exercise/physical activity and vascular endothelial function, assessed via flow mediated dilation. Studies were categorized by sex: male-only, female-only, or mixed sex, including examination of the sample size of males and females. Analysis was performed examining sex-inclusion criteria in study design and reporting and rationale for inclusion/exclusion of participants on the basis of sex. Changes in proportion of female participants included in studies were examined over time in 5 year cohorts.ResultsA total of 514 studies were identified, spanning 26 years (1996–2021). Of the total participants, 64% were male and 36% were female, and a male bias was identified (32% male-only vs. 12% female-only studies). Proportions of female participants in studies remained relatively constant in the last 20 years. Male-only studies were less likely to report sex in the title compared to female-only studies (27 vs. 78%, p &lt; 0.001), report sex in the abstract (72 vs. 98%, p &lt; 0.001) and justify exclusion on the basis of sex (15 vs. 55%, p &lt; 0.001). Further, male-only studies were more likely to be conducted in healthy populations compared to female-only studies (p = 0.002). Qualitative analysis of justifications identified four themes: sex-specific rationale or gap in the literature, exclusion of females based on the hormonal cycle or sex-differences, maintaining congruence with the male norm, and challenges with recruitment, retention and resources.ConclusionsThis systematic review provides the first analysis of sex-based inclusion/exclusion and rationale for sex-based decisions in human vascular exercise physiology research. These findings contribute to identifying the impact of research guidelines regarding inclusion of males and females and the perceived barriers to designing studies with equal sex participation, in an effort to increase female representation in vascular exercise physiology research.Systematic Review Registration:CRD42022300388.

Passive leg movement (PLM) elicits rapid vasodilation in the microvasculature that is primarily dependent on nitric oxide. PLM‐induced vasodilation (PLM‐D) therefore, provides an index of lower‐limb microvascular endothelial function. PLM‐D is lower in advanced aging and clinical populations vs. young and healthy controls, demonstrating that PLM‐D provides a useful assessment of vascular responses. However, there is currently limited information regarding the reliability of PLM‐D and no information on the reliability of PLM‐D in women. Therefore, the purpose of this study was to test the hypothesis that PLM‐D in women is reliable when measured over two separate days. Seventeen, young healthy women (22 ± 3 yrs) participated in two identical experimental visits during the early follicular (low‐estrogen) phase of the menstrual cycle. Each visit included three standardized trials of PLM involving one minute of baseline, two minutes of PLM and two minutes of recovery. During the two minutes of PLM an experimenter moved the participant's leg from 90° flexion to 180° extension and back at a set pace of 1 cycle/s. Using duplex ultrasound PLM‐D was characterized by six commonly utilized factors; peak leg blood flow (LBF) and vascular conductance (LVC), peak change above baseline (Δpeak) for LBF and LVC, and area under the curve above baseline (ΔAUC) during the first 60s of PLM for LBF and LVC. The day‐to‐day reliability of PLM‐D was quantified by calculating the Pearson correlation coefficient (r value), intraclass correlation coefficient (ICC) and coefficient of variation (CV). The results demonstrated good day‐to‐day reliability of PLM‐D characterized as peak LBF (r = 0.84, p < 0.001; ICC = 0.84; CV = 13.2%), peak LVC (r = 0.82, p < 0.001; ICC = 0.79; CV = 14.4%), Δpeak LBF (r = 0.83, p < 0.001; ICC = 0.82; CV = 17.8%) and Δpeak LVC (r = 0.83, p < 0.001; ICC = 0.80; CV = 16.5%). Characterization of PLM as ΔAUC demonstrated moderate day‐to‐day reliability; ΔAUC LBF (r = 0.71, p< 0.05; ICC = 0.70; CV = 31.2%) and ΔAUC LVC (r = 0.78, p < 0.001; ICC = 0.74; CV = 27.1%). In conclusion, this study demonstrates that PLM‐D has good day‐to‐day reliability, however, characterization of PLM‐D as peak and Δpeak LBF and LVC is more reliable than ΔAUC. These findings support the use of PLM‐D in future studies as a reliable method to assess lower‐limb microvascular endothelial function in women.

New Findings What is the topic of this review?The aim of this systematic review was to evaluate and summarize all published literature examining the impact of various exercise training interventions on endothelial function in postmenopausal women. What advances does it highlight?There was a moderate effect of training on macrovascular and microvascular endothelial function and just under two‐thirds of studies demonstrated a significant increase in at least one measure of endothelial function in postmenopausal women. Factors including exercise intensity and duration, vessel type, clinical status, hormone therapy, and menopausal status may influence the effects of training on endothelial function in postmenopausal women. Abstract Women experience a rapid decline in endothelial function during menopause. Therefore, it is important to explore interventions, such as exercise training, that may prevent endothelial dysfunction in postmenopausal women. The aim of this systematic review was to evaluate and summarize all published literature examining the impact of various exercise training interventions on endothelial function in postmenopausal women. Three electronic databases (MEDLINE, EMBASE and Web of Science) were used to systematically select studies related to exercise training, endothelial function and postmenopausal women. The major initial and secondary update systematic searches yielded 502 unique articles that were screened for eligibility. Thirty‐five studies were included in the systematic review. Two‐thirds of all studies demonstrated a group‐level increase in at least one measure of endothelial function with training. Most studies investigating biomarkers of endothelial function showed improvement in at least one measured biomarker post‐training. There was a moderate effect of training on both macrovascular and microvascular endothelial function in observational and randomized intervention studies. Variability in study designs, training protocols and participant characteristics make it difficult to directly compare studies. Factors including exercise intensity and duration, vessel type, clinical status, hormone therapy, and menopausal status may contribute to the inconsistent effects of training on endothelial function in postmenopausal women. Future research is needed in this population to understand the mechanisms driving inter‐study and inter‐individual differences in training‐induced changes in endothelial function.