IMPACT OF SEX ON MACROVASCULAR ENDOTHELIAL FUNCTION DURING PROLONGED SITTING WITH A MILD HYPERCAPNIC ENVIRONEMNT

IMPACT OF SEX ON MACROVASCULAR ENDOTHELIAL FUNCTION DURING PROLONGED SITTING WITH A MILD HYPERCAPNIC ENVIORNMENT Andres Benitez-Albiter1, Michael F. Allen1, Elizabeth J. Pekas1, Cody P. Anderson1, and Song-Young Park1 1 - School of Health & Kinesiology University of Nebraska Omaha, Omaha, NE Introduction: Prolonged sitting (PS), defined as sitting for 2+ hours at a time[SYP1] , has been identified as an independent risk factor for cardiovascular disease. It has been well-documented that an acute PS bout can impair macro- and microvascular dysfunction in healthy young individuals. Recently, we reported that PS in mild hypercapnic environments (elevated CO2 concentrations equivalent to crowded areas such as offices or auditoriums) can further exacerbate these impairments in healthy young adults, and these impairments can be partially prevented by intermittent bouts of passive and active leg movements. Office workers are one of the largest sectors of the US workforce, and have been reported to be frequently exposed to PS with mild hypercapnic environments. Therefore, there is a need of study to examine if our previous findings can be seen in office workers. Additionally, it is crucial to investigate if there is any differential contribution of biological sex on these findings. The purpose of this study was to examine the impact of active and passive muscular contraction on macrovascular endothelial function during PS with mild-hypercapnic environment in middle-aged office workers, and further compare potential differences between sex. Methods: Healthy office workers (n=13, 6 males and 7 females, 39±4, 41±9, respectively) participated in three experimental visits and consisted of 2.5 h of prolonged sitting in a mild-hypercapnic environment (CO2 = 1500 ppm): control (CON, no movement), passive (PASS, passive limb movement), and active (ACT, active limb movement). Brachial artery and popliteal artery endothelial function were measured pre- and post-sitting for all visits using flow-mediated dilation (FMD). Results: Following 2.5 h of sitting, ACT showed greater popliteal artery FMD compared to CON. Additionally, females exhibited a significant reduction in popliteal artery FMD in the CON but was preserved in males after PS. No changes in Brachial artery FMD after PS, and no sex difference was found. Conclusion: PS significantly reduces leg vascular function in middle-aged office workers. Additionally, females showed greater reduction in leg vascular function compared to males. We conclude that uninterrupted prolonged sitting may induce a greater impairment on leg vascular function in females, indicating that this population may be at a greater risk compared to males. Additionally, intermittent bouts of active movement required to preserve leg vascular function during bouts of PS

Endothelial cell Nrf2-KO attenuates endothelial function and skeletal muscle antioxidant capacity

INTRODUCTION: Endothelial cells line the inner surface of blood vessels and play a major role in modulating blood flow and gas exchange. Endothelial dysfunction is thought to be a contributor to cardiovascular disease development, and it is well-accepted that excessive reactive oxygen species (harmful molecules) likely contribute to endothelial dysfunction. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered the master regulator of cellular protection in response to elevated reactive oxygen species. Therefore, Nrf2 may be a potential therapeutic target to protect against endothelial dysfunction. However, the roles of endothelial cell-specific Nrf2 on endothelial function are not known. The purpose of this study was to investigate the impacts of endothelial cell-specific Nrf2 deletion on vascular function (endothelium-dependent and endothelium-independent vasodilation) and skeletal muscle antioxidant status. METHODS: Leg arteries were harvested from 6-mo old C57BL/6 mice (WT, n = 6) and endothelial cell-specific Nrf2-knockout mice (Tie2-Cre-Nrf2 floxed-KO, n = 6). Endothelium-dependent vasodilation was assessed in response to flow (30 uL·min-1) and acetylcholine (ACh, 10-7-10-3 M) with and without Nω-Nitro-L-arginine methyl ester (L-NAME), and endothelium-independent vasodilation was assessed with sodium nitroprusside (SNP, 10-9-10-4 M) using videomicroscopy. Skeletal muscle antioxidant protein expression for glutathione peroxidase-1 (GPX-1) and catalase (CAT) was assessed by immunoblotting. RESULTS: Endothelium-dependent vasodilation was lower in Nrf2-KO compared to WT induced by flow (WT: 34.8±2.9%, Nrf2-KO: 20.7±3.7%, P-3M, WT: 68.3±8.2%, Nrf2-KO: 44.5±7.1%, PP-3 M, 19.1±4.4%, PP=0.28) or ACh (10-3 M, 37.7±7.0%, P = 0.16). Endothelium-independent vasodilation was not different (SNP 10-4 M, WT: 92.7±3.6%, Nrf2-KO: 81.9± 0.2%, P=0.157). In addition, GPX-1 was lower in Nrf2-KO mice (WT: 0.47±0.06, Nrf2-KO: 0.001±0.003, PP=0.08). CONCLUSIONS: Endothelial cell Nrf2 may play a key role in endothelial-mediated vasodilatory function. The nitric oxide synthase inhibitor L-NAME attenuated endothelial-mediated vasodilation in WT but not in endothelial cell Nrf2-KO. Furthermore, endothelial cell Nrf2 may play a role in skeletal muscle antioxidant homeostasis, which suggests potential systemic implications of endothelial cell Nrf2 deletion. These results collectively suggest that the endothelial cell Nrf2 system is linked to endothelial dysfunction and changes in the skeletal muscle redox environment, likely through nitric oxide- and oxidative stress-related mechanisms

Cardiovascular and Autonomic Responses to Acute Exposure to Mild Hypercapnic Conditions in Middle-Aged Adults

Sedentary lifestyle in the US has significantly increased in recent decades, specifically, adults in modern workplaces have been known to be exposed to ~6 hours of uninterrupted prolonged sitting (PS) per day. PS has been shown to cause endothelial dysfunction, leading to an increased risk for cardiovascular disease such as peripheral arterial disease. Additionally, elevations in carbon dioxide (hypercapnia), commonly observed in workplaces such as offices, have been known to impair cardiovascular function. Interrupting PS with muscular contractions has been used to prevent the negative effects of PS. However, the underlying protective mechanism(s) of these muscular contractions during PS with hypercapnia in middle-aged adults is currently unknown. The purpose of this study was to examine the impacts of muscle contraction, specifically, activation of group III/IV muscle afferents via passive and active leg movement in middle-aged office workers during PS in a mild-hypercapnic environment. Healthy sedentary middle-aged adults (n=5, age: 45 ± 9) completed 3 visits in a mild-hypercapnic environment: control (CON) passive (PASS) and active (ACT) to determine how activating group III/IV muscle afferents during 2.5 hours of PS affect cardiovascular function. Following PS, popliteal shear rate increased in ACT (23.98%) compared to PASS (4.09%) and CON (11.44%). Popliteal artery flow-mediated dilation showed greater increase in ACT (3.33%) compared to PASS (1.44%) and CON (1.12%). This study provides novel insight towards the cardiovascular effects of PS with mild hypercapnia in sedentary middle-aged adults, and the roles of group III and IV muscle afferent activation in the preservation for vascular function