Effects of Excess Sodium Consumption on Arterial Function in C57BL/6 Mice.

Excess sodium consumption contributes to arterial dysfunction in humans. The C57BL/6 strain of mice have been used to identify mechanisms by which arterial dysfunction occurs after excess sodium consumption. However, there are concerns that C57BL/6 mice have strain-specific resistance to high-sodium (HS) diet-induced hypertension. To address this concern, we performed a meta-analysis to determine if excess sodium consumption in C57BL/6 mice induces arterial dysfunction. Databases were searched for HS vs. standard diet studies that measured arterial function (i.e., systolic blood pressure [BP], endothelium-dependent dilation [EDD], and central arterial stiffness) in C57BL/6 mice. A total of 39 studies were included, demonstrating that HS condition resulted in higher systolic BP than control mice with a mean difference of 9.8 mmHg (95% CI [5.6, 14], P<0.001). Subgroup analysis indicated that the systolic BP was higher in HS compared to the control condition when measured during night compared to daytime with telemetry (P<0.001). We also identified that the difference in systolic BP between HS and control was ~2.5-fold higher when administered through drinking water than through food (P<0.001). A total of 12 studies were included, demonstrating that HS condition resulted in lower EDD than control with a weighted mean difference of -12.0% (95% CI [-20.0, -4.1], P=0.003). It should be noted that there was considerable variability across studies with more than half of the studies showing no effect of HS condition on systolic BP and EDD. In summary, excess sodium consumption elevates systolic BP and impairs EDD in C57BL/6 mice.

High-salt diet augments systolic blood pressure and induces arterial dysfunction in outbred, genetically diverse mice.

Excess salt consumption contributes to hypertension and arterial dysfunction in humans living in industrialized societies. However, this arterial phenotype is not typically observed in inbred, genetically identical mouse strains that consume a high-salt (HS) diet. Therefore, we sought to determine the effects of HS diet consumption on systolic blood pressure (BP) and arterial function in UM-HET3 mice, an outbred, genetically diverse strain of mice. Male and female UM-HET3 mice underwent a low-salt [LS (1% NaCl)] or HS (4% NaCl) diet for 12 wk. Systolic BP and aortic stiffness, determined by pulse wave velocity (PWV), were increased in HS after 2 and 4 wk, respectively, compared with baseline and continued to increase through week 12 (P < 0.05). Systolic BP was higher from weeks 2-12 and PWV was higher from weeks 4-12 in HS compared with LS mice (P < 0.05). Aortic collagen content was ∼81% higher in HS compared with LS (P < 0.05), whereas aortic elastin content was similar between groups (P > 0.05). Carotid artery endothelium-dependent dilation (EDD) was ∼10% lower in HS compared with LS (P < 0.05), endothelium-independent dilation was similar between groups (P > 0.05). Finally, there was a strong relationship between systolic BP and PWV (r2 = 0.40, P < 0.05), as well as inverse relationship between EDD and systolic BP (r2 = 0.21, P < 0.05) or PWV (r2 = 0.20, P < 0.05). In summary, HS diet consumption in UM-HET3 mice increases systolic BP, which is accompanied by aortic stiffening and impaired EDD. These data suggest that outbred, genetically diverse mice may provide unique translational insight into arterial adaptations of humans that consume an HS diet.NEW & NOTEWORTHY Excess salt consumption is a contributor to hypertension and arterial dysfunction in humans living in industrialized societies, but this phenotype is not observed in inbred, genetically identical mice that consume a high-salt (HS) diet. This study reveals that a HS diet in outbred, genetically diverse mice progressively increases systolic blood pressure and induce arterial dysfunction. These data suggest that genetically diverse mice may provide translational insight into arterial adaptations in humans that consume an HS diet.

Therapeutic strategies targeting the endothelial glycocalyx.

PURPOSE OF REVIEW: This review will highlight recent studies that have examined the endothelial glycocalyx in a variety of health conditions, as well as potential glycocalyx-targeted therapies. RECENT FINDINGS: A degraded glycocalyx is present in individuals that consume high sodium diet or have kidney disease, diabetes, preeclampsia, coronavirus disease 2019 (COVID-19), or sepsis. Specifically, these conditions are accompanied by elevated glycocalyx components in the blood, such as syndecan-1, syndecans-4, heparin sulfate, and enhanced heparinase activity. Impaired glycocalyx barrier function is accompanied by decreased nitric oxide bioavailability, increased leukocyte adhesion to endothelial cells, and vascular permeability. Glycocalyx degradation appears to play a key role in the progression of cardiovascular complications. However, studies that have used glycocalyx-targeted therapies to treat these conditions are scarce. Various therapeutics can restore the glycocalyx in kidney disease, diabetes, COVID-19, and sepsis. Exposing endothelial cells to glycocalyx components, such as heparin sulfate and hyaluronan protects the glycocalyx. SUMMARY: We conclude that the glycocalyx is degraded in a variety of health conditions, although it remains to be determined whether glycocalyx degradation plays a causal role in disease progression and severity, and whether glycocalyx-targeted therapies improve patient health outcomes. Future studies are warranted to investigate therapeutic strategies that target the endothelial glycocalyx.

Effect of eccentric and concentric contraction mode on myogenic regulatory factors expression in human vastus lateralis muscle.

Skeletal muscle contractions are caused to release myokines by muscle fiber. This study investigated the myogenic regulatory factors, as MHC I, IIA, IIX, Myo-D, MRF4, Murf, Atrogin-1, Decorin, Myonection, and IL-15 mRNA expression in the response of eccentric vs concentric contraction. Eighteen healthy men were randomly divided into two eccentric and concentric groups, each of 9 persons. Isokinetic contraction protocols included maximal single-leg eccentric or concentric knee extension tasks at 60°/s with the dominant leg. Contractions consisted of a maximum of 12 sets of 10 reps, and the rest time between each set was 30 s. The baseline biopsy was performed 4 weeks before the study, and post-test biopsies were taken immediately after exercise protocols from the vastus lateralis muscle. The gene expression levels were evaluated using Real-Time PCR methods. The eccentric group showed a significantly lower RPE score than the concentric group (P ≤ 0.05). A significant difference in MyoD, MRF4, Myonection, and Decorin mRNA, were observed following eccentric or concentric contractions (P ≤ 0.05). The MHC I, MHC IIA, IL-15 mRNA has been changed significantly compared to the pre-exercise in the concentric group (P ≤ 0.05). While only MHC IIX and Atrogin-1 mRNA changed significantly in the eccentric group (P ≤ 0.05). Additionally, the results showed a significant difference in MyoD, MRF4, IL-15, and Decorin at the follow-up values between eccentric or concentric groups (P ≤ 0.05). Our findings highlight the growing importance of elucidating the different responses of muscle growth factors associated with a myogenic activity such as MHC IIA, Decorin, IL-15, Myonectin, Decorin, MuRF1, and MHC IIX mRNA in following various types of exercise.

Inflammatory, antioxidant and glycemic status to different mode of high-intensity training in type 2 diabetes mellitus.

BACKGROUND: Exercise has traditionally been used and prescribed as an effective and suitable way to treat type 2 diabetics Mellitus (T2DM). In this regard, we compared inflammatory, antioxidant, and glycemic status to different kinds of high-intensity interval training (strength training, HIIT, and HIIT + ST) in patients with T2DM. METHODS AND RESULTS: Fifty-nine T2DM patients (age = 45-60 yrs) were randomly divided to strength training (ST) (n = 15), high intensity interval training (HIIT) (n = 16), HIIT + ST (n = 15) or served as control (CON) (n = 13) groups. Experimental groups performed three training sessions/week for 12 weeks. Inflammatory, antioxidant, glycemic factors, and anthropometric parameters were evaluated at baseline and after the 12 weeks of interventions. Training HIIT groups significantly improved antioxidant factors, lipid profile, and glycemic parameters (P ≤ 0.05). Interleukin 6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) significantly decreased in the three training groups. As a result of training, the overall inflammatory and antioxidant status were improved considerably in all three training groups compared to the CON group (P ≤ 0.05). In addition, there were significant differences in CRP at the follow-up values between ST and CON groups (P ≤ 0.05). Exercise time and TC were significantly improved in HIIT than in the CON group (P ≤ 0.05). The results showed a significant difference between the HIIT + ST group and the CON group in VO2peak (P ≤ 0.05). CONCLUSIONS: Our results showed improvement in inflammatory factors, antioxidants, and glycemic parameters in all training groups regardless of their type. However, for more benefits in T2DM patients, combination exercises can be suggested.

Effect of different muscle contraction mode on the expression of Myostatin, IGF-1, and PGC-1 alpha family members in human Vastus Lateralis muscle.

Muscle contraction stimulates a transient change of myogenic factors, partly related to the mode of contractions. Here, we assessed the response of IGF-1Ea, IGF-1Eb, IGF-1Ec, PGC1α-1, PGC1α-4, and myostatin to the eccentric Vs. the concentric contraction in human skeletal muscle. Ten healthy males were performed an acute eccentric and concentric exercise bout (n = 5 per group). For each contraction type, participants performed 12 sets of 10 repetitions knee extension by the dominant leg. Baseline and post-exercise muscle biopsy were taken 4 weeks before and immediately after experimental sessions from Vastus Lateralis muscle. Genes expression was measured by real-time PCR technique. There was a significant increase in PGC1α-1, PGC1α-4, IGF-1Ea and, IGF-1Eb mRNA after concentric contraction (p ≤ 0.05), while the PGC1α-4 and IGF-1Ec significantly increased after eccentric contraction (p ≤ 0.05). It is intriguing to highlight that; no significant differences between groups were evident for changes in any variables following exercise bouts (p ≥ 0.05). Our results found that concentric and eccentric contractions presented different responses in PGC1α-1, IGF-1Ea, IGF-1Eb, and IGF-1Ec mRNA. However, a similar significant increase in mRNA content was observed in PGC1α-4. Further, no apparent differences could be found between the response of genes to eccentric and concentric contraction.

High-intensity interval training improves the vascular endothelial function comparing moderate-intensity interval training in overweight or obese adults: A meta-analysis.

OBJECTIVE: Obesity is associated with endothelial dysfunction and cardiovascular diseases. Moderate-intensity continuous training (MICT) is a common method to improve endothelial function and the cardiovascular risk profile in obesity. However, in recent times, high-intensity interval training (HIIT) has become a popular alternative for MICT primarily because of its time efficiency. Therefore, we hypothesized that HIIT is superior to MICT in improving vascular function. We aimed to evaluate this hypothesis by conducting a meta-analysis and quantifying the effect of HIIT on flow-mediated dilation (FMD) in overweight/obese adults. METHODS: Databases (Scopus, Web of Science, and PubMed) were searched up to January 2022 for HIIT vs. moderate-intensity interval training (MICT) and HIIT vs. control (CON) studies on endothelial function assessed by flow-mediated dilation (FMD) in overweight and obese adults. From the included studies, standardized mean difference (SMD) and 95% confidence intervals (95% CIs) were calculated. RESULTS: 8 studies with 208 participants were included in this meta-analysis. According to the 6 studies, HIIT improved the FMD with an overall change of %2.6 [(95% CI: 0.82 to 4.377), p = 0.004] compared to the MICT in overweight and obese adults. Moreover, based on the 5 studies that compared HIIT and CON, the results showed HIIT significantly increased FMD by 1.83% [(95% CI: 0.478 to 3.187), p = 0.008]. CONCLUSIONS: These results showed that exercise training, particularly HIIT, could improve endothelial function in overweight and obese adults.

Associations between physical activity levels with nutritional status, physical fitness and biochemical indicators in older adults.

BACKGROUND & AIMS: A sedentary lifestyle is one of the major health concerns of all societies that is associated by an increased risk of cardiovascular diseases. In this regard, we compared the anthropometric parameters, physical fitness (PF), lipid profile, and nutritional status of older adults with different levels of physical activity (PA). METHODS: In this cross sectional study, 220 older people (age: 67.39 ± 2.08 yrs) according to their PA levels had been categorized at high (n = 72), moderate (78) and low (n = 70) PA groups. The International Physical Activity Questionnaires and food frequency questionnaire has been used to determine the PA and nutritional status, respectively. Waist and hip circumference, height, weight, and body mass index of subjects were measured and calculated. Both lower and upper body strength, flexibility, static and dynamic balance, and endurance performance factors were used to determine the level of PF. To assess blood biochemical factors, subjects were asked to visit the laboratory after 12 h of fasting. RESULTS: The results showed waist circumference, hip circumference, and body fat percent were significantly lower in the high PA group compared to the low PA group in both males and females (P ≤ 0.05). Upper body strength, lower body strength, static balance, dynamic balance flexibility and endurance were significantly better in the high PA group compared to the low PA group in both males and females (P ≤ 0.05). Moreover, triglyceride was significantly lower in the high PA group compared to the low PA group in both males and females (P ≤ 0.05). According to the post hoc results, high-density lipoprotein, low-density lipoprotein and fasting glucose were significantly better in the high PA group compared to the low PA group in both males and females (P ≤ 0.05). All participants regardless PA levels showed insufficient consumption of zinc, calcium, vitamin E, and vitamin D (P ≤ 0.05). On the other hand, carbohydrate, sodium, iron, vitamin C and niacin intake significantly above recommended dietary allowance (P ≤ 0.05). CONCLUSIONS: The results of the current work showed that a higher level of PA improved anthropometric indicators, PF, and lipid profile in Iranian older adults. Moreover, older nutrition should be monitor to maintain their physical health and to prevent them from developing chronic diseases and their malnutrition complications.

Comparing High-Intensity Interval Training (HIIT) and Continuous Training on Apelin, APJ, NO, and Cardiotrophin-1 in Cardiac Tissue of Diabetic Rats.

BACKGROUND AND AIMS: Exercise activity is an important method for managing type 2 diabetes. This investigation examined the HIIT and continuous training on apelin, APJ receptor, NO, and cardiotrophin-1 in the cardiac tissue of diabetic rats. METHODS: The animals were categorized into 3 groups of HIIT, continuous (CO), and control (C) (all animals were sacrificed immediately and 2 days after exercise training period). Rats underwent the treadmill exercise program either HIIT (12 bouts at 90-95% of VO2 max with 60 s rest at 50% of VO2 max) or CO (60-65% VO2 max for 40 min). Protocols performed 5 days per week for 8 weeks. Apelin, APJ receptor, NO, and cardiotrophin-1 protein expressions were measured using the Western blotting method in the left ventricle. RESULTS: Immediately after HIIT and CO exercise protocols, apelin and CT-1 protein showed a significant difference in contrast by the C-0 group (p < 0.01). However, NO values were substantially higher in HIIT-0 compared to C-0 and CO-0 groups rats (p < 0.01). After two days of exercise protocols, apelin and NO protein showed a significant increase in HIIT and CO groups in contrast to the C animals (p < 0.01). Moreover, APJ and CT-1 protein significantly upregulated in CO-2 and HIIT-2 compared to the other groups (p < 0.01). CONCLUSIONS: This study indicates that exercise training, despite the type, is an efficient method to modify apelin, APJ receptor, NO, and cardiotrophin-1 values in animals with type 2 diabetes.

Moderate treadmill exercise improves spatial learning and memory deficits possibly via changing PDE-5, IL-1 ß and pCREB expression.

Alzheimer's is a progressive disorder of the nervous system. Prior studies suggested that physical activity contributes to the improvement of cognitive impairment and slows down pathogenesis of AD; however, the exact mechanisms for this have not been fully understood. Therefore, in this study, we examined the effect of aerobic training before and after induction of Alzheimer's on spatial learning and memory, expression of interleukin-1 beta (IL-1ß), cAMP-responsive element-binding protein (pCREB), and Phosphodiesterase-5 (PDE-5) in the hippocampus of male rats Wistar. Aß was microinjected into the CA1 area of the hippocampus animals. The moderate treadmill exercise protocols for pre and post induction of Alzheimer's were the same (5 days/week, for 4 weeks with a customized regime). The Morris Water Maze (MWM) method has been to assess spatial learning and memory. The real time-PCR method was used to measure gene expression. Our results showed that intra-hippocampal injection of Aß1-42 impaired spatial learning and memory which was accompanied by reduced pCREB activity and elevated IL-1ß and PDE-5 in the hippocampus of rats. In contrast, moderate treadmill exercise ameliorated the Aß1-42-induced spatial learning and memory deficit, which was accompanied by restored pCREB activity and decreasing IL-1ß and PDE-5 levels. In conclusion, our finding suggests that exercise before and after Alzheimer's induction leads to an increase in pCREB and an alleviation of inflammation which likely involved in ameliorating spatial learning and memory deficits in an animal model of AD.