Arterial function in response to a 50 km ultramarathon in recreational athletes.

This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave-reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points-Baseline (BL), following 10, 20, 30 and 40 km, 1 h post-completion (1HP) and 24 h post-completion (24HP). Flow-mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P < 0.001 for both) and reactive hyperaemia was higher at 24HP (∼27%) compared with BL (P = 0.018). Compared to BL, both mean central systolic BP and mean central diastolic BP were 7% and 10% higher, respectively, following 10 km and 6% and 9% higher, respectively, following 20 km, and then decreased by 5% and 8%, respectively, at 24HP (P < 0.05 for all). AIx (%) decreased following 20 km and following 40 km compared with BL (P < 0.05 for both) but increased following 40 km when corrected for HR (AIx75) compared with BL (P = 0.02). Forward wave amplitude significantly increased at 10 km (15%) compared with BL (P = 0.049), whereas backward wave reflection and reflected magnitude were similar at all time points. FMD and baseline diameter remained similar. These data indicate preservation of macrovascular (endothelial) function, but not microvascular function resulting from the 50 km ultramarathon.

Acute inflammation elicits decreased blood pressure but similar arterial stiffness in young African American adults.

African Americans (AA) have a higher risk for cardiovascular disease (CVD) as compared to their White (W) counterparts. CVD is characterized by increased blood pressure (BP), arterial stiffness and systemic inflammation. An acute inflammatory stimulus may explain physiological manifestations responsible for amplified CVD in AA that are not apparent at rest. The purpose of this study was to evaluate central and peripheral BP, central and local arterial stiffness, and indices of pulse wave morphology in young healthy AA and W participants in response to acute inflammation. Concentrations of the inflammatory cytokine interleukin-6 (IL-6) and measures of central and peripheral BP, central arterial stiffness (carotid-femoral pulse wave velocity (cfPWV)), local carotid arterial stiffness (ß-stiffness, elastic modulus (Ep)), and indices of pulse wave morphology were assessed in 28 participants (21 ± 2 years, AA: n = 11) at baseline (BL), 24 h and 48 h post-inflammation. Changes in IL-6 concentrations (ΔIL-6) were significantly greater at 24 h as compared to 48 h post-inflammation (0.652 ± 0.644 vs. -0.146 ± 0.532 pg/µl, P ≤ 0.0001). Among AA participants, central and peripheral diastolic BP were significantly decreased at 24 h post-inflammation as compared to BL (aortic diastolic BP: -4 ± 4 mmHg, P = 0.016; brachial diastolic BP: -4 ± 4 mmHg, P = 0.014). AA participants also experienced a significant decrease in central and peripheral mean arterial BP at 48 h post-inflammation as compared to BL (aortic mean arterial pressure: -4 ± 4 mmHg, P = 0.009; brachial mean arterial pressure: -4 ± 4 mmHg, P = 0.012). Despite haemodynamic changes, there were no differences in central or local carotid arterial stiffness or indices of pulse wave morphology.

Naturally menstruating women exhibit lower cardiovagal baroreflex sensitivity than oral contraceptive users during the lower hormone phase.

The present study evaluated cardiovagal baroreflex sensitivity (BRS) across the menstrual/pill cycle in naturally menstruating women (NAT women) and women using oral hormonal contraceptives (OCP women). In 21 NAT women (23 ± 4 years old) and 22 OCP women (23 ± 3 years old), cardiovagal BRS and circulating concentrations of estradiol and progesterone were evaluated during the lower hormone (early follicular/placebo pill) and higher hormone (late follicular to early luteal/active pill) phases. During the lower hormone phase, cardiovagal BRS up, down and mean gain were lower in NAT women (15.6 ± 8.3, 15.2 ± 6.1 and 15.1 ± 7.1 ms/mmHg) compared with OCP women (24.7 ± 9.4, 22.9 ± 8.0 and 23.0 ± 8.0 ms/mmHg) (P = 0.003, P = 0.002 and P = 0.003, respectively), and higher oestrogen (R2  = 0.15, P = 0.024), but not progesterone (R2  = 0.06, P = 0.18), concentrations were predictive of lower BRS mean gain. During the higher hormone phase, higher progesterone concentrations were predictive of lower BRS mean gain (R2  = 0.12, P = 0.024). A multivariate regression model revealed group (NAT or OCP) to be a significant predictor of cardiovagal BRS mean gain in the lower hormone phase when hormone concentrations were adjusted for (R2  = 0.36, P = 0.0044). The multivariate regression model was not significant during the higher hormone phase (P > 0.05). In summary, cardiovagal BRS is lower in NAT compared with OCP women during the lower hormone phase of the menstrual/pill cycle and might be associated with higher oestrogen concentrations. In contrast, during the higher hormone phase of the menstrual/OCP cycle, higher progesterone concentrations were predictive of lower cardiovagal BRS. NEW FINDINGS: What is the central question of this study? Does cardiovagal baroreflex sensitivity (BRS) differ between naturally menstruating women (NAT women) and women using oral contraceptives (OCP women)? What is the main finding and its importance? The main findings are as follows: (1) NAT women exhibit lower cardiovagal BRS than OCP women during the lower hormone phase of the menstrual or pill cycle; and (2) circulating oestrogen concentrations are significant predictors of cardiovagal BRS during the lower hormone phase, with higher oestrogen concentrations predicting lower BRS. The present data advance our understanding of the effect of endogenous ovarian hormones and OCP use on cardiovascular control mechanisms.

Heart rate variability between hormone phases of the menstrual and oral contraceptive pill cycles of young women.

INTRODUCTION: The interplay between the sympathetic and parasympathetic branches of the autonomic nervous system contribute to adequate hemodynamic responses to stressors, reflected by the variation in intervals between heart beats, known as heart rate variability. The sex hormones estrogen and progesterone have been shown to affect autonomic function. The extent to which autonomic function may vary between different hormone phases of the natural menstrual cycle and how this relationship may differ in women taking oral contraceptives has yet to be fully elucidated. PURPOSE: To investigate differences in heart rate variability between the early follicular and early luteal phases of the menstrual cycle in naturally menstruating women and in oral contraceptive pill users. METHODS: Twenty-two young (22 ± 3 years), healthy women who were naturally menstruating or taking oral contraceptive pills participated in this study. Heart rate variability was measured at rest and during two sympathomimetic stressors: isometric handgrip exercise and cold pressor test. RESULTS: The proportion of successive NN intervals that differ by more than 50 ms was higher in oral contraceptive pill users during the placebo pill phase. Absolute high-frequency power was higher in the naturally menstruating women during the early luteal phase, relative to the early follicular phase. Other indices of vagal modulation were not different at rest or during sympathetic activation between hormone phases or groups. CONCLUSIONS: Vagal modulation may be increased in the early luteal menstrual cycle phase. Further,oral contraceptive use does not appear to adversely affect this modulation in young, healthy women.

Arterial stiffness and blood pressure are similar in naturally menstruating and oral contraceptive pill-using women during the higher hormone phases.

NEW FINDINGS: What is the central question of this study? Are there differences in blood pressure, arterial stiffness and indices of pressure waveforms between young oral contraceptive pill-using and naturally menstruating women during lower and higher hormone phases of their cycles? What is the main finding and its importance? Blood pressure, arterial stiffness and indices of pressure waveforms are influenced similarly by exogenous and endogenous hormones. However, lower levels of exogenous hormones moderately increase blood pressure among oral contraceptive pill-using women. ABSTRACT: Elevations in blood pressure (BP) are understood as having a bidirectional relationship with stiffening of central and peripheral arteries. Arterial stiffness is mitigated by oestrogen, which aides in arterial vasorelaxation. To evaluate whether BP, stiffness, and pressure waveforms were different between young healthy naturally menstruating (non-OCP) and oral contraceptive pill (OCP)-using women, we measured brachial and aortic BPs, carotid-to-femoral pulse wave velocity, carotid ß-stiffness, elastic modulus, central augmentation index and augmentation index normalized to a heart rate of 75 bpm, and forward and backward pressure waveforms in 22 women (22 (1) years, OCP: n = 12). To assess phasic differences, women were studied during the early follicular (≤5 days of menstruation onset) and early luteal (4 (2) days post-ovulation) phases of non-OCP and compared to the placebo pill (≤5 days of onset) and active pill (≤5 days of highest-dose active pill) phases of OCP. During the lower hormone phases, OCP users had significantly higher brachial systolic blood pressure (SBP) (119.3 (8.3) vs. 110.2 (8.3) mmHg, P = 0.02) and aortic SBP (104.10 (7.44) vs. 96.80 (6.39) mmHg, P = 0.03) as compared to non-OCP users; however, during the higher hormone phases, there were no differences in measures of brachial or aortic BP, arterial stiffness, or indices of BP waveforms between OCP and non-OCP users (P ≥ 0.05). In conclusion, exogenous and endogenous hormones have similar influences on BP and arterial stiffness; however, lower levels of exogenous hormones augment both central and peripheral BPs.

Similar inflammatory response and conduit artery vascular function between sexes following induced inflammation.

NEW FINDINGS: What is the central question of this study? Are there sex differences in vascular function following induced inflammation when oestrogen is typically similar between sexes? What is the main finding and its importance? The present study suggests no sex differences in conduit artery vascular responses to acutely induced inflammation during the low-oestrogen phase of the menstrual cycle in premenopausal women. However, women exhibit lower microvascular function than men. Overall, the results underpin the role of oestrogen in previously observed sex differences and the importance of reporting the phase in the hormonal cycle when women are studied. ABSTRACT: Sex differences in cardiovascular disease incidence in premenopausal women and age-matched men have been attributed to the cardioprotective influence of oestrogen. However, limited knowledge exists regarding sex differences following acute inflammation when oestrogen concentrations are lower in women. We evaluated sex differences in vascular responses to induced inflammation when oestrogen concentrations are typically lower in women (early follicular phase or placebo phase of hormonal contraception). In 15 women and 14 men, interleukin-6 (IL-6) concentrations and vascular function [via brachial artery flow-mediated dilatation (FMD)] were assessed at baseline (BL) and 24 (24H) and 48 hours (48H) after administration of influenza vaccine. After induction of inflammation, both sexes exhibited an increase in IL-6 concentrations at 24H [mean (SD) BL vs. 24H: women, 0.563 (0.50) vs. 1.141 (0.65) pg/ml; men, 0.385 (0.17) vs. 1.113 (0.69) pg/ml; P < 0.05] that returned to near-baseline concentrations by 48H (BL vs. 48H, P > 0.05). There were no sex differences in FMD, allometrically scaled FMD or IL-6 concentrations at any time point (P > 0.05). Notably, women exhibited significantly lower microvascular function than men at every time point [P < 0.05; reactive hyperaemic area under the curve (in arbitrary units): women, BL 35,512 (14,916), 24H 34,428 (14,292) and 48H 39,467 (13,936); men, BL 61,748 (27,324), 24H 75,028 (29,051) and 48H 59,532 (13,960)]. When oestrogen concentrations are typically lower in women, women exhibit a similar inflammatory response and conduit artery function, but lower microvascular response to reactive hyperaemia, in comparison to age-matched men.

Interleukin-6 is higher in naturally menstruating women compared with oral contraceptive pill users during the low-hormone phase.

Endogenous sex hormone concentrations vary between healthy naturally menstruating (non-OCP) and oral contraceptive pill-using (OCP) women, as well as across cycles. The aim of this study was to investigate potential differences in concentrations of inflammatory cytokine interleukin-6 (IL-6) and vasoconstrictive substance endothelin-1 (ET-1) and measures of vascular function among relatively lower- and higher-hormone phases of non-OCP and OCP women. Concentrations of estrogen, progesterone, IL-6, and ET-1 and measures of vascular function were collected in 22 women (22 ± 1 yr, OCP: n = 12) during the early follicular (EF, ≤5 days of menstruation onset) and early luteal (EL, 4 ± 2 days postovulation) phases of non-OCP subjects and were compared to the placebo pill (PP, ≤5 days of PP onset) and active pill (AP, ≤5 days of highest-dose AP) phases of OCP subjects. Vascular function was assessed via brachial artery flow-mediated dilation (%FMD). Concentrations of endogenous estrogen and progesterone were higher in the EL phase compared with the EF phase of non-OCP (P = 0.01) but were similar between phases of OCP (P > 0.05). IL-6 was higher in non-OCP during the EF phase compared with the EL phase (P = 0.03) as well as compared with OCP during the PP phase (P = 0.002) but was similar between groups during the EL and AP phases, respectively (P > 0.05). Concentrations of ET-1 and measures of %FMD were similar between groups and unaffected by phase (P > 0.05). Thus, there exists variation in inflammation between young, healthy non-OCP and OCP women during the lower-hormone phase, despite similarities in vascular function and concentrations of ET-1 between groups and phases.NEW & NOTEWORTHY We demonstrate that despite having similar macrovascular function and concentrations of the vasoconstrictive substance endothelin-1 (ET-1) healthy naturally menstruating women display higher concentrations of circulating IL-6 during the lower-hormone phase of their menstrual cycle compared with 1) the higher-hormone phase of their menstrual cycle and 2) the lower-hormone phase of healthy women using oral contraceptive pills.

Race-specific changes in endothelial inflammation and microRNA in response to an acute inflammatory stimulus.

Both aberrant vascular reactivity to acute cardiovascular stress and epigenetic mechanisms such as microRNA (miR) may underlie the increased propensity for African Americans (AA) to develop cardiovascular disease. This study assessed racial differences in acute induced endothelial inflammation and related miRs. Cultured human umbilical vein endothelial cells (HUVECs) derived from AA and Caucasian Americans (CA) were exposed to influenza vaccine to determine changes in inflammatory markers, endothelial nitric oxide synthase (eNOS), and miR expression/release. Endothelial function [flow-mediated dilation (FMD)], circulating IL-6, and circulating miR were also measured in young, healthy AA and CA individuals before and after receiving the influenza vaccine. There were no significant racial differences in any parameters at baseline. The vaccine induced increases in IL-6 release (24%, P = 0.02) and ICAM-1 mRNA (40%, P = 0.03), as well as reduced eNOS mRNA (24%, P = 0.04) in AA HUVECs, but not in CA HUVECs (all P > 0.05). Intracellular levels of anti-inflammatory miR-221-3p and miR-222-3p increased specifically in CA HUVECs (72% and 53%, P = 0.04 and P = 0.06), whereas others did not change in either race. HUVEC secretion of several miRs decreased in both races, whereas the release of anti-inflammatory miR-150-5p was decreased only by AA cells (-30%, P = 0.03). In individuals of both races, circulating IL-6 increased approximately twofold 24 h after vaccination (both P < 0.01) and returned to baseline levels by 48 h, whereas FMD remained unchanged. Although macrovascular function was unaffected by acute inflammation in AA and CA individuals, AA endothelial cells exhibited increased susceptibility to acute inflammation and unique changes in related miR.NEW & NOTEWORTHY Used as an acute inflammatory stimulus, the influenza vaccine induced an inflammatory response and decreased eNOS gene expression in endothelial cells derived from African Americans, but not Caucasian Americans. Race-specific changes in intracellular expression and release of specific microRNAs also occurred and may contribute to an exaggerated inflammatory response in African Americans. In vivo, the vaccine caused similar systemic inflammation but had no effect on endothelial function or circulating microRNAs in individuals of either race.

Changes in circulating microRNA and arterial stiffness following high-intensity interval and moderate intensity continuous exercise.

High-intensity interval (HII) exercise elicits distinct vascular responses compared to a matched dose of moderate intensity continuous (MOD) exercise. However, the acute effects of HII compared to MOD exercise on arterial stiffness are incompletely understood. Circulating microRNAs (ci-miRs) may contribute to the vascular effects of exercise. We sought to determine exercise intensity-dependent changes in ci-miR potentially underlying changes in arterial stiffness. Ten young, healthy men underwent well-matched, 30-min HII and MOD exercise bouts. RT-qPCR was used to determine the levels of seven vascular-related ci-miRs in serum obtained immediately before and after exercise. Arterial stiffness measures including carotid to femoral pulse wave velocity (cf-PWV), carotid arterial compliance and ß-stiffness, and augmentation index (AIx and AIx75) were taken before, 10min after and 60min after exercise. Ci-miR-21-5p, 126-3p, 126-5p, 150-5p, 155-5p, and 181b-5p increased after HII exercise (p < .05), while ci-miR-150-5p and 221-3p increased after MOD exercise (p = .03 and 0.056). One hour after HII exercise, cf-PWV trended toward being lower compared to baseline (p = .056) and was significantly lower compared to 60min after MOD exercise (p = .04). Carotid arterial compliance was increased 60min after HII exercise (p = .049) and was greater than 60min after MOD exercise (p = .02). AIx75 increased 10 min after both HII and MOD exercise (p < .05). There were significant correlations between some of the exercise-induced changes in individual ci-miRs and changes in cf-PWV and AIx/AIx75. These results support the hypotheses that arterial stiffness and ci-miRs are altered in an exercise intensity-dependent manner, and ci-miRs may contribute to changes in arterial stiffness.

The effects of moderate and high-intensity exercise on circulating markers of endothelial integrity and activation in young, healthy men.

Endothelial function typically exhibits a hormetic response to exercise. It is unknown whether endothelial damage occurs in response to acute exercise and could be a contributing mechanism. We sought to determine the effects of acute exercise on endothelial-derived circulating factors proposed to reflect endothelial integrity and activation. Young, healthy men (n = 10) underwent 30-min moderate continuous (MOD) and high-intensity interval (HII) cycling exercise bouts. Venous blood samples were taken immediately before and after exercise for quantification of circulating endothelial cells (CECs), circulating angiogenic cells (CACs), apoptotic and activated endothelial microvesicles (EMVs), thrombomodulin (TM), von Willebrand factor (vWF), syndecan-1, and circulating microRNAs (ci-miRs) 126-3p and 126-5p. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery before, 10 min after, and 60 min after exercise. Numbers of CECs and EMVs were unchanged by either exercise bout (P > 0.05). Numbers of all measured CAC subtypes decreased in response to MOD (21%-34%, P < 0.05), whereas only CD31+/34+/45dim/- CACs decreased following HII (21%, P < 0.05). TM and syndecan-1 increased with both exercise intensities (both ~20%, P < 0.05). HII, but not MOD, increased vWF (88%, P < 0.001), ci-miR-126-3p (92%, P = 0.009) and ci-miR-126-5p (110%, P = 0.01). The changes in several circulating factors correlated with changes in FMD following either one or both intensities. Changes in circulating factors do not support the concept of exercise-induced endothelial cell denudation, apoptosis, or activation, though slight disruption of endothelial glycocalyx and membrane integrity may occur. A related loss of mechanotransduction along with mechanisms underlying endothelial activation and ci-miR-126 secretion may relate to changes in endothelial function.NEW & NOTEWORTHY Using circulating endothelial-derived factors, we show that endothelial denudation, apoptosis, and activation do not appear to increase, whereas disrupted endothelial glycocalyx and membrane integrity may occur during both high-intensity interval and moderate intensity cycling. Increases in factors nonspecific to endothelial damage, including von Willebrand factor and microRNA-126, occurred only after high-intensity interval exercise. These results shed light on the hypothesis that disrupted endothelial integrity contributes to the endothelial function response to exercise.