Gonadal status modulates large elastic artery stiffness in healthy middle-aged and older men.

Hypogonadism is a risk factor for cardiovascular disease (CVD) in men related, in part, to increased oxidative stress. Elevated large artery stiffness and central pulsatile hemodynamics (e.g., pulse pressure and wave reflection magnitude) are independent risk factors for CVD. However, whether large artery stiffness and central pulsatile hemodynamics are (1) elevated in hypogonadal men independent of traditional CVD risk factors and (2) related to increased oxidative stress is unknown. Young men (N = 23; 30 ± 4 years) and middle-aged/older (MA/O) men with normal (> 400-1000 ng/dL; n = 57; 59 ± 7 years) or low testosterone (< 300 ng/dL; n = 21; 59 ± 7 years) underwent assessments of large artery stiffness (carotid ß-stiffness via ultrasonography) and central pulsatile hemodynamics (pulse wave analysis; SphygmoCor XCEL) following an infusion of saline or vitamin C to test the tonic suppression of vascular function by oxidative stress. Carotid stiffness differed by age (p < 0.001) and gonadal status within MA/O men (low testosterone vs. normal testosterone: 9.3 ± 0.7 vs. 8.0 ± 0.3U, p = 0.036). Central pulsatile hemodynamics did not differ by age or gonadal status (p > 0.119). Vitamin C did not alter carotid stiffness in any group (p > 0.171). There was a significant group × infusion interaction on aortic reflection magnitude (p = 0.015). Vitamin C treatment reduced aortic reflection magnitude in young and MA/O men with normal testosterone (both p < 0.001) but not MA/O men with low testosterone (p = 0.891). Collectively, hypogonadism may accelerate age-related large artery stiffening in MA/O men with low testosterone, independent of CVD risk factors; however, this is not related to increased reactive oxygen species sensitive to an acute vitamin C infusion.

Adjusting for muscle strength and body size attenuates sex differences in the exercise pressor reflex in young adults.

Females typically exhibit lower blood pressure (BP) during exercise than males. However, recent findings indicate that adjusting for maximal strength attenuates sex differences in BP during isometric handgrip (HG) exercise and postexercise ischemia (PEI; metaboreflex isolation). In addition, body size is associated with HG strength but its contribution to sex differences in exercising BP is less appreciated. Therefore, the purpose of this study was to determine whether adjusting for strength and body size would attenuate sex differences in BP during HG and PEI. We obtained beat-to-beat BP in 110 participants (36 females, 74 males) who completed 2 min of isometric HG exercise at 40% of their maximal voluntary contraction followed by 3 min of PEI. In a subset (11 females, 17 males), we collected muscle sympathetic nerve activity (MSNA). Statistical analyses included independent t tests and mixed models (sex × time) with covariate adjustment for 40% HG force, height2, and body surface area. Females exhibited a lower absolute 40% HG force than male participants (Ps < 0.001). Females exhibited lower Δsystolic, Δdiastolic, and Δmean BPs during HG and PEI than males (e.g., PEI, Δsystolic BP, 15 ± 11 vs. 23 ± 14 mmHg; P = 0.004). After covariate adjustment, sex differences in BP responses were attenuated. There were no sex differences in MSNA. In a smaller strength-matched cohort, there was no sex × time interactions for BP responses (e.g., PEI systolic BP, P = 0.539; diastolic BP, P = 0.758). Our data indicate that sex differences in exercising BP responses are attenuated after adjusting for muscle strength and body size.NEW & NOTEWORTHY When compared with young males, females typically exhibit lower blood pressure (BP) during exercise. Adjusting for maximal strength attenuates sex differences in BP during isometric handgrip (HG) exercise and postexercise ischemia (PEI), but the contribution of body size is unknown. Novel findings include adjustments for muscle strength and body size attenuate sex differences in BP reactivity during exercise and PEI, and sex differences in body size contribute to HG strength differences.

Short-term high-salt consumption does not influence resting or exercising heart rate variability but increases MCP-1 concentration in healthy young adults.

High salt consumption increases blood pressure (BP) and cardiovascular disease risk by altering autonomic function and increasing inflammation. However, it is unclear whether salt manipulation alters resting and exercising heart rate variability (HRV), a noninvasive measure of autonomic function, in healthy young adults. The purpose of this investigation was to determine whether short-term high-salt intake 1) alters HRV at rest, during exercise, or exercise recovery and 2) increases the circulating concentration of the inflammatory biomarker monocyte chemoattractant protein 1 (MCP-1). With the use of a randomized, placebo-controlled, crossover study, 20 participants (8 females; 24 ± 4 yr old, 110 ± 10/64 ± 8 mmHg) consumed salt (3,900 mg sodium) or placebo capsules for 10 days each separated by ≥2 wk. We assessed HRV during 10 min of baseline rest, 50 min of cycling (60% V̇o2peak), and recovery. We quantified HRV using the standard deviation of normal-to-normal RR intervals, the root mean square of successive differences (RMSSD), and additional time and frequency domain metrics of HRV. Plasma samples were collected to assess MCP-1 concentration. No main effect of high salt or condition × time interaction was observed for HRV metrics. However, acute exercise reduced HRV (e.g., RMSSD time: P < 0.001, condition: P = 0.877, interaction: P = 0.422). High salt elevated plasma MCP-1 (72.4 ± 12.5 vs. 78.14 ± 14.7 pg/mL; P = 0.010). Irrespective of condition, MCP-1 was moderately associated (P values < 0.05) with systolic (r = 0.32) and mean BP (r = 0.33). Short-term high-salt consumption does not affect HRV; however, it increases circulating MCP-1, which may influence BP in young adults.

Age-associated reductions in cardiovagal baroreflex sensitivity are exaggerated in middle-aged and older men with low testosterone.

Aging is associated with reductions in cardiovagal baroreflex sensitivity (cBRS), which increases cardiovascular disease risk. Preclinical data indicate that low testosterone reduces cBRS. We determined whether low testosterone is associated with greater age-associated reductions in cBRS in healthy men. Twenty-six men categorized as young (N = 6; age = 31 ± 4 yr; testosterone = 535 ± 60 ng/dL), middle-aged/older with normal (N = 10; aged 56 ± 3 yr; testosterone = 493 ± 85 ng/dL) or low (N = 10; age = 57 ± 6 yr; testosterone = 262 ± 31 ng/dL) testosterone underwent recordings of beat-by-beat blood pressure and R-R interval during rest and two Valsalva maneuvers, and measures of carotid artery compliance. IL-6, C-reactive protein (CRP), oxidized LDL cholesterol, and total antioxidant status (TAS) were also measured in blood. Middle-aged/older men had lower cBRS compared with young men (17.0 ± 6.5 ms/mmHg; P = 0.028); middle-age/older men with low testosterone had lower cBRS (5.5 ± 3.2 ms/mmHg; P = 0.039) compared with age-matched men with normal testosterone (10.7 ± 4.0 ms/mmHg). No differences existed between groups during Phase II of the Valsalva maneuver; middle-aged/older men with low testosterone had reduced cBRS (4.7 ± 2.6 ms/mmHg) compared with both young (12.8 ± 2.8 ms/mmHg; P < 0.001) and middle-aged/older men with normal testosterone (8.6 ± 4.4 ms/mmHg; P = 0.046). There were no differences in oxidized LDL (P = 0.882) or TAS across groups (P = 0.633). IL-6 was significantly higher in middle-aged/older men with low testosterone compared with the other groups (P < 0.05 for all) and inversely correlated with cBRS (r = -0.594, P = 0.007). Middle-aged/older men had reduced carotid artery compliance compared with young, regardless of testosterone status (P < 0.001). These observations indicate that low testosterone in middle-aged/older men may contribute to reductions in cBRS. These data suggest that increased inflammation may contribute to reductions in cBRS.NEW & NOTEWORTHY Middle-aged/older men with low testosterone have accelerated reductions in cardiovagal BRS compared with middle-aged/older men with normal testosterone. Increased concentrations of the proinflammatory cytokine IL-6 appear to contribute to the reductions in cardiovagal BRS in men with low testosterone.

High dietary salt intake increases urinary NGAL excretion and creatinine clearance in healthy young adults.

In rodents and older patients with elevated blood pressure (BP), high dietary sodium increases excretion of biomarkers of kidney injury, but it is unclear whether this effect occurs in healthy young adults. The purpose of this study was to determine whether short-term high dietary salt increases urinary excretion of the kidney injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in healthy young adults. Twenty participants participated in a double-blind, placebo-controlled, randomized crossover study. For 10 days each, participants were asked to consume salt (3,900 mg sodium) or placebo capsules. We measured BP during each visit, obtained 24-h urine samples for measurements of electrolytes, NGAL, and KIM-1, and assessed creatinine clearance. Compared with placebo, salt loading increased daily urinary sodium excretion (placebo: 130.3 ± 62.4 mmol/24 h vs. salt: 287.2 ± 72.0 mmol/24 h, P < 0.01). There was no difference in mean arterial BP (placebo: 77 ± 7 mmHg vs. salt: 77 ± 6 mmHg, P = 0.83) between conditions. However, salt loading increased the urinary NGAL excretion rate (placebo: 59.8 ± 44.4 ng/min vs. salt: 80.8 ± 49.5 ng/min, P < 0.01) and increased creatinine clearance (placebo: 110.5 ± 32.9 mL/min vs. salt: 145.0 ± 24.9 mL/min, P < 0.01). Urinary KIM-1 excretion was not different between conditions. In conclusion, in healthy young adults 10 days of dietary salt loading increased creatinine clearance and increased urinary excretion of the kidney injury biomarker marker NGAL but not KIM-1.NEW & NOTEWORTHY In healthy young adults, 10 days of dietary salt loading increased creatinine clearance and increased urinary excretion of the kidney injury biomarker marker neutrophil gelatinase-associated lipocalin despite no change in resting blood pressure.

Oxidative Stress and Inflammation Are Associated With Age-Related Endothelial Dysfunction in Men With Low Testosterone.

CONTEXT: Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-aged/older men is associated with increased CVD risk. OBJECTIVE: We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. METHODS: This cross-sectional study included 58 healthy, nonsmoking men categorized as young (N = 20; age 29 ± 4 years; testosterone 500 ± 58 ng/dL), middle-aged/older with higher testosterone (N = 20; age 60 ± 6 years; testosterone 512 ± 115 ng/dL), and middle-aged/older lower testosterone (N = 18; age 59 ± 8 years; testosterone 269 ± 48 ng/dL). Brachial artery flow-mediated dilation (FMDBA) was measured during acute infusion of saline (control) and vitamin C (antioxidant). Markers of oxidative stress (total antioxidant status and oxidized low-density lipoprotein cholesterol), inflammation (interleukin [IL]-6 and C-reactive protein [CRP]), and androgen deficiency symptoms were also examined. RESULTS: During saline, FMDBA was reduced in middle-aged/older compared with young, regardless of testosterone status (P < 0.001). FMDBA was reduced in middle-aged/older lower testosterone (3.7% ± 2.0%) compared with middle-aged/older higher testosterone (5.7% ± 2.2%; P = 0.021), independent of symptoms. Vitamin C increased FMDBA (to 5.3% ± 1.6%; P = 0.022) in middle-aged/older lower testosterone but had no effect in young (P = 0.992) or middle-aged/older higher testosterone (P = 0.250). FMDBA correlated with serum testosterone (r = 0.45; P < 0.001), IL-6 (r = -0.41; P = 0.002), and CRP (r = -0.28; P = 0.041). CONCLUSION: Healthy middle-aged/older men with low testosterone appear to have greater age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. These data suggest that low testosterone concentrations may contribute to accelerated vascular aging in men.

Ten days of high dietary sodium does not impair cerebral blood flow regulation in healthy adults.

High dietary sodium impairs cerebral blood flow regulation in rodents and is associated with increased stroke risk in humans. However, the effects of multiple days of high dietary sodium on cerebral blood flow regulation in humans is unknown. Therefore, the purpose of this study was to determine whether ten days of high dietary sodium impairs cerebral blood flow regulation. Ten participants (3F/7M; age: 30 ± 10 years; blood pressure (BP): 113 ± 8/62 ± 9 mmHg) participated in this randomized, cross-over design study. Participants were placed on 10-day diets that included either low- (1000 mg/d), medium- (2300 mg/d) or high- (7000 mg/d) sodium separated by ≥four weeks. Urinary sodium excretion, beat-to-beat BP (finger photoplethysmography), middle cerebral artery velocity (transcranial Doppler), and end-tidal carbon dioxide (capnography) was measured. Dynamic cerebral autoregulation during a ten-minute baseline was calculated and cerebrovascular reactivity assessed by determining the percent change in middle cerebral artery blood flow velocity to hypercapnia (8% CO2, 21% oxygen, balance nitrogen) and hypocapnia (via mild hyperventilation). Urinary sodium excretion increased in a stepwise manner (ANOVA P = 0.001) from the low, to medium, to high condition. There were no differences in dynamic cerebral autoregulation between conditions. While there was a trend for a difference during cerebrovascular reactivity to hypercapnia (ANOVA P = 0.06), this trend was abolished when calculating cerebrovascular conductance (ANOVA: P = 0.28). There were no differences in cerebrovascular reactivity (ANOVA P = 0.57) or conductance (ANOVA: P = 0.73) during hypocapnia. These data suggest that ten days of a high sodium diet does not impair cerebral blood flow regulation in healthy adults.

Assessment of macrovascular and microvascular function in aging males.

Aging is associated with reductions in endothelial function, observations primarily reported using brachial artery ultrasound. There is growing interest in the use of peripheral artery tonometry (PAT) of microvessels in the fingertip to assess endothelial function because it is less technically demanding and has a high sensitivity and specificity for assessing coronary endothelial function. Moreover, similar to brachial artery flow-mediated dilation (FMD), PAT predicts cardiovascular disease outcomes. However, the relationship between PAT and FMD have yet to be examined in the context of aging. To address this question, reactive hyperemic index (RHI) using EndoPAT and FMD using brachial artery ultrasound were assessed after 5 min of forearm ischemia in 20 younger (18-40 yr old; 29 ± 4 yr) and 20 older (60-75 yr old; 65 ± 4 yr) healthy adult men. Higher values of both FMD and RHI indicate better endothelial function. Endothelial function assessed via brachial artery FMD was lower in older (4.8 ± 2.1%), compared with younger (7.5 ± 1.6%) men (P < 0.001). In contrast, the RHI assessed via PAT was greater in older (2.2 ± 0.6), compared with younger (1.8 ± 0.5) men (P = 0.014). FMD and RHI were not correlated (r = -0.15; P = 0.35). We conclude that PAT may not be an appropriate measure to evaluate age-associated changes in endothelial function.NEW & NOTEWORTHY Microvessel endothelial function assessed via finger plethysmography may not reflect age-associated reductions in large artery endothelial function assessed via brachial artery flow-mediated dilation.

A high salt meal does not impair cerebrovascular reactivity in healthy young adults.

A high sodium (Na+ ) meal impairs peripheral vascular function. In rodents, chronic high dietary Na+ impairs cerebral vascular function, and in humans, habitual high dietary Na+ is associated with increased stroke risk. However, the effects of acute high dietary Na+ on the cerebral vasculature in humans are unknown. The purpose of this study was to determine if acute high dietary Na+ impairs cerebrovascular reactivity in healthy adults. Thirty-seven participants (20F/17M; 25 ± 5 years; blood pressure [BP]: 107 ± 9/61 ± 6 mm Hg) participated in this randomized, cross-over study. Participants were given a low Na+ meal (LSM; 138 mg Na+ ) and a high Na+ meal (HSM; 1,495 mg Na+ ) separated by ≥ one week. Serum Na+ , beat-to-beat BP, middle cerebral artery velocity (transcranial Doppler), and end-tidal carbon dioxide (PET CO2 ) were measured pre- (baseline) and 60 min post-prandial. Cerebrovascular reactivity was assessed by determining the percent change in middle cerebral artery velocity to hypercapnia (via 8% CO2 , 21% oxygen, balance nitrogen) and hypocapnia (via mild hyperventilation). Peripheral vascular function was measured using brachial artery flow-mediated dilation (FMD). Changes in serum Na+ were greater following the HSM (HSM: Δ1.6 ± 1.2 mmol/L vs. LSM: Δ0.7 ± 1.2 mmol/L, p < .01). Cerebrovascular reactivity to hypercapnia (meal effect: p = .41) and to hypocapnia (meal effect: p = .65) were not affected by the HSM. Contrary with previous findings, FMD was not reduced following the HSM (meal effect: p = .74). These data suggest that a single high Na+ meal does not acutely impair cerebrovascular reactivity, and suggests that despite prior findings, a single high Na+ meal does not impair peripheral vascular function in healthy adults.

Short-term water deprivation attenuates the exercise pressor reflex in older female adults.

Older adults have reduced fluid intake and impaired body fluid and electrolyte regulation. Older female adults exhibit exaggerated exercise blood pressure (BP) responses, which is associated with an increased risk of adverse cardiovascular events. However, it is unclear if dysregulated body fluid homeostasis contributes to altered exercise BP responses in older female adults. We tested the hypothesis that short-term water deprivation (WD) increases exercise BP responses in older female adults. Fifteen female adults (eight young [25 ± 6 years] and seven older [65 ± 6 years]) completed two experimental conditions in random crossover fashion; a euhydration control condition and a stepwise reduction in water intake over three days concluding with a 16-hr WD period. During both trials, beat-to-beat BP (photoplethysmography) and heart rate (electrocardiogram) were continuously assessed during rest, handgrip exercise (30% MVC), and post-exercise ischemia (metaboreflex isolation). At screening, older compared to young female adults had greater systolic and diastolic BP (p ≤ .02). Accelerometer-assessed habitual physical activity was not different between groups (p = .65). Following WD, 24-hr urine flow rate decreased, whereas thirst, urine specific gravity, and plasma osmolality increased (condition: p < .05 for all), but these WD-induced changes were not different between age groups (interaction: p ≥ .31 for all). Resting systolic and diastolic BP values were higher in older compared to young adults (p < .01 for both), but were not different between experimental conditions (p ≥ .20). In contrast to our hypothesis, WD was associated with attenuated systolic BP responses during handgrip exercise (post hoc: p < .01) and post-exercise ischemia (post hoc: p = .03) in older, but not young, female adults. These data suggest that reduced water intake-induced challenges to body fluid homeostasis do not contribute to exaggerated exercise BP responses in post-menopausal female adults.

High Salt Intake Augments Blood Pressure Responses During Submaximal Aerobic Exercise.

Background High sodium (Na+) intake is a widespread cardiovascular disease risk factor. High Na+ intake impairs endothelial function and exaggerates sympathetic reflexes, which may augment exercising blood pressure (BP) responses. Therefore, this study examined the influence of high dietary Na+ on BP responses during submaximal aerobic exercise. Methods and Results Twenty adults (8F/12M, age=24±4 years; body mass index 23.0±0.6 kg·m-2; VO2peak=39.7±9.8 mL·min-1·kg-1; systolic BP=111±10 mm Hg; diastolic BP=64±8 mm Hg) participated in this randomized, double-blind, placebo-controlled crossover study. Total Na+ intake was manipulated via ingestion of capsules containing either a placebo (dextrose) or table salt (3900 mg Na+/day) for 10 days each, separated by ≥2 weeks. On day 10 of each intervention, endothelial function was assessed via flow-mediated dilation followed by BP measurement at rest and during 50 minutes of cycling at 60% VO2peak. Throughout exercise, BP was assessed continuously via finger photoplethysmography and every 5 minutes via auscultation. Venous blood samples were collected at rest and during the final 10 minutes of exercise for assessment of norepinephrine. High Na+ intake increased urinary Na+ excretion (placebo=140±68 versus Na+=282±70 mmol·24H-1; P<0.001) and reduced flow-mediated dilation (placebo=7.2±2.4 versus Na+=4.2±1.7%; P<0.001). Average exercising systolic BP was augmented following high Na+ (placebo=Δ30.0±16.3 versus Na+=Δ38.3±16.2 mm Hg; P=0.03) and correlated to the reduction in flow-mediated dilation (R=-0.71, P=0.002). Resting norepinephrine concentration was not different between conditions (P=0.82). Norepinephrine increased during exercise (P=0.002), but there was no Na+ effect (P=0.26). Conclusions High dietary Na+ augments BP responses during submaximal aerobic exercise, which may be mediated, in part, by impaired endothelial function.

Sex differences in vascular aging in response to testosterone.

Large elastic arterial stiffening and endothelial dysfunction are phenotypic characteristics of vascular aging, a major risk factor for age-associated cardiovascular diseases. Compared to men, vascular aging in women appears to be slowed until menopause, whereafter vascular aging accelerates to match that seen in men. These sex differences in vascular aging have been attributed to changes in sex hormones that occur with aging. Although the role of estradiol in vascular aging in women has been highlighted in recent aging research, little is known about the impact of declining testosterone concentrations in both sexes. Importantly, while androgen concentrations generally decline with age in men, there are data that indicate reductions in androgen concentrations in women as well. Evidence suggests that low testosterone is associated with impaired endothelial function and increased arterial stiffness in men, although the effect of androgens on vascular aging in women remains unclear. Testosterone may modulate vascular aging by mitigating the effects of oxidative stress and inflammation, although there is sex specificity to this effect. The purpose of this review is to present and summarize the research regarding sex differences in vascular aging in response to androgens, specifically testosterone. Because exercise is a potent lifestyle factor for slowing and reversing vascular aging, we briefly summarize the available literature regarding the regulatory function of testosterone on vascular adaptations to exercise training.

Effects of Whey Protein Supplementation on Aortic Stiffness, Cerebral Blood Flow, and Cognitive Function in Community-Dwelling Older Adults: Findings from the ANCHORS A-WHEY Clinical Trial.

ANCHORS A-WHEY was a 12-week randomized controlled trial (RCT) designed to examine the effect of whey protein on large artery stiffness, cerebrovascular responses to cognitive activity and cognitive function in older adults. METHODS: 99 older adults (mean ± SD; age 67 ± 6 years, BMI 27.2 ± 4.7kg/m2, 45% female) were randomly assigned to 50g/daily of whey protein isolate (WPI) or an iso-caloric carbohydrate (CHO) control for 12 weeks (NCT01956994). Aortic stiffness was determined as carotid-femoral pulse wave velocity (cfPWV). Aortic hemodynamic load was assessed as the product of aortic systolic blood pressure and heart rate (Ao SBP × HR). Cerebrovascular response to cognitive activity was assessed as change in middle-cerebral artery (MCA) blood velocity pulsatility index (PI) during a cognitive perturbation (Stroop task). Cognitive function was assessed using a computerized neurocognitive battery. RESULTS: cfPWV increased slightly in CHO and significantly decreased in WPI (p < 0.05). Ao SBP × HR was unaltered in CHO but decreased significantly in WPI (p < 0.05). Although emotion recognition selectively improved with WPI (p < 0.05), WPI had no effect on other domains of cognitive function or MCA PI response to cognitive activity (p > 0.05 for all). CONCLUSIONS: Compared to CHO, WPI supplementation results in favorable reductions in aortic stiffness and aortic hemodynamic load with limited effects on cognitive function and cerebrovascular function in community-dwelling older adults.

The Impact of High Dietary Sodium Consumption on Blood Pressure Variability in Healthy, Young Adults.

BACKGROUND: High sodium (Na+) intake augments blood pressure variability (BPV) in normotensive rodents, without changes in resting blood pressure (BP). Augmented BPV is associated with end-organ damage and cardiovascular morbidity. It is unknown if changes in dietary Na+ influence BPV in humans. We tested the hypothesis that high Na+ feeding would augment BPV in healthy adults. METHODS: Twenty-one participants (10 F/11 M; 26 ± 5 years; BP: 113 ± 11/62 ± 7 mm Hg) underwent a randomized, controlled feeding study that consisted of 10 days of low (2.6 g/day), medium (6.0 g/day), and high (18.0 g/day) salt diets. On the ninth day of each diet, 24-h urine samples were collected and BPV was calculated from 24-h ambulatory BP monitoring. On the tenth day, in-laboratory beat-to-beat BPV was calculated during 10 min of rest. Serum electrolytes were assessed. We calculated average real variability (ARV) and standard deviation (SD) as metrics of BPV. As a secondary analysis, we calculated central BPV from the 24-h ambulatory BP monitoring. RESULTS: 24-h urinary Na+ excretion (low = 41 ± 24, medium = 97 ± 43, high = 265 ± 92 mmol/24 h, P < 0.01) and serum Na+ (low = 140.0 ± 2.1, medium = 140.7 ± 2.7, high = 141.7 ± 2.5 mmol/l, P = 0.009) increased with greater salt intake. 24-h ambulatory ARV (systolic BP ARV: low = 9.5 ± 1.7, medium = 9.5 ± 1.2, high = 10.0 ± 1.9 mm Hg, P = 0.37) and beat-to-beat ARV (systolic BP ARV: low = 2.1 ± 0.6, medium = 2.0 ± 0.4, high = 2.2 ± 0.8 mm Hg, P = 0.46) were not different. 24-h ambulatory SD (systolic BP: P = 0.29) and beat-to-beat SD (systolic BP: P = 0.47) were not different. There was a trend for a main effect of the diet (P = 0.08) for 24-h ambulatory central systolic BPV. CONCLUSIONS: Ten days of high sodium feeding does not augment peripheral BPV in healthy, adults. CLINICAL TRIALS REGISTRATION: NCT02881515.

Salt Loading Blunts Central and Peripheral Postexercise Hypotension.

INTRODUCTION: High salt intake is a widespread cardiovascular risk factor with systemic effects. These effects include an expansion of plasma volume, which may interfere with postexercise hypotension (PEH). However, the effects of high salt intake on central and peripheral indices of PEH remain unknown. We tested the hypothesis that high salt intake would attenuate central and peripheral PEH. METHODS: Nineteen healthy adults (7 female/12 male; age, 25 ± 4 yr; body mass index, 23.3 ± 2.2 kg·m; V[Combining Dot Above]O2peak, 41.6 ± 8.7 mL·min·kg; systolic blood pressure (BP), 112 ± 9 mm Hg; diastolic BP, 65 ± 9 mm Hg) participated in this double-blind, randomized, placebo-controlled crossover study. Participants were asked to maintain a 2300 mg·d sodium diet for 10 d on two occasions separated by ≥2 wk. Total salt intake was manipulated via ingestion of capsules containing either table salt (3900 mg·d) or placebo (dextrose) during each diet. On the 10th day, participants completed 50 min of cycling at 60% V[Combining Dot Above]O2peak. A subset of participants (n = 8) completed 60 min of seated rest (sham trial). Beat-to-beat BP was measured in-laboratory for 60 min after exercise via finger photoplethysmography. Brachial and central BPs were measured for 24 h after exercise via ambulatory BP monitor. RESULTS: Ten days of high salt intake increased urinary sodium excretion (134 ± 70 (dextrose) vs 284 ± 74 mmol per 24 h (salt), P < 0.001), expanded plasma volume (7.2% ± 10.8%), and abolished PEH during in-laboratory BP monitoring (main effect of diet, P < 0.001). Ambulatory systolic BPs were higher for 12 h after exercise during the salt and sham trials compared with the dextrose trial (average change, 3.6 ± 2.1 mm Hg (dextrose), 9.9 ± 1.4 mm Hg (salt), 9.8 ± 2.5 mm Hg (sham); P = 0.01). Ambulatory central systolic BP was also higher during the salt trial compared with dextrose trial. CONCLUSION: High salt intake attenuates peripheral and central PEH, potentially reducing the beneficial cardiovascular effects of acute aerobic exercise.

Short-term water deprivation does not increase blood pressure variability or impair neurovascular function in healthy young adults.

High dietary salt increases arterial blood pressure variability (BPV) in salt-resistant, normotensive rodents and is thought to result from elevated plasma [Na+] sensitizing central sympathetic networks. Our purpose was to test the hypothesis that water deprivation (WD)-induced elevations in serum [Na+] augment BPV via changes in baroreflex function and sympathetic vascular transduction in humans. In a randomized crossover fashion, 35 adults [17 female/18 male, age: 25 ± 4 yr, systolic/diastolic blood pressure (BP): 107 ± 11/60 ± 7 mmHg, body mass index: 23 ± 3 kg/m2] completed two hydration protocols: a euhydration control condition (CON) and a stepwise reduction in water intake over 3 days, concluding with 16 h of WD. We assessed blood and urine electrolyte concentrations and osmolality, resting muscle sympathetic nerve activity (MSNA; peroneal microneurography; 18 paired recordings), beat-to-beat BP (photoplethysmography), common femoral artery blood flow (Doppler ultrasound), and heart rate (single-lead ECG). A subset of participants (n = 25) underwent ambulatory BP monitoring during day 3 of each protocol. We calculated average real variability as an index of BPV. WD increased serum [Na+] (141.0 ± 2.3 vs. 142.1 ± 1.7 mmol/L, P < 0.01) and plasma osmolality (288 ± 4 vs. 292 ± 5 mosmol/kg H2O, P < 0.01). However, WD did not increase beat-to-beat (1.9 ± 0.4 vs. 1.8 ± 0.4 mmHg, P = 0.24) or ambulatory daytime (9.6 ± 2.1 vs. 9.4 ± 3.3 mmHg, P = 0.76) systolic BPV. Additionally, sympathetic baroreflex sensitivity (P = 0.20) and sympathetic vascular transduction were not different after WD (P = 0.17 for peak Δmean BP following spontaneous MSNA bursts). These findings suggest that, despite modestly increasing serum [Na+], WD does not affect BPV, arterial baroreflex function, or sympathetic vascular transduction in healthy young adults.

A high-salt meal does not augment blood pressure responses during maximal exercise.

Augmented blood pressure (BP) responses during exercise are predictive of future cardiovascular disease. High dietary sodium (Na+) increases BP responses during static exercise. It remains unclear if high dietary Na+ augments BP responses during dynamic exercise. The purpose of this study was to test the hypothesis that an acute high-Na+ meal would augment BP responses during dynamic exercise. Twenty adults (10 male/10 female; age, 26 ± 5 years; BP, 105 ± 10/57 ± 6 mm Hg) were given a high-Na+ meal (HSM; 1495 mg Na+) and a low-Na+ meal (LSM; 138 mg Na+) separated by at least 1 week, in random order. Serum Na+ and plasma osmolality were measured. Eighty minutes following the meal, participants completed a graded-maximal exercise protocol on a cycle ergometer. Heart rate, beat-by-beat BP, cardiac output, total peripheral resistance, and manual BP were measured at rest and during exercise. Both serum Na+ (HSM: Δ1.6 ± 2.0 vs LSM: Δ1.1 ± 1.8 mmol/L, P = 0.0002) and plasma osmolality (HSM: Δ3.0 ± 4.5 vs LSM: Δ2.0 ± 4.2 mOsm/(kg·H2O), P = 0.01) were higher following the HSM. However, the HSM did not augment BP during peak exercise (systolic BP: HSM: 170 ± 23 vs LSM: 171 ± 21 mm Hg, P = 0.81). These findings suggest that an acute high-salt meal does not augment BP responses during dynamic exercise in adults. Novelty The high-salt meal increased serum sodium and plasma osmolality compared with the low-salt meal. The high-salt meal did not augment blood pressure responses during maximal dynamic exercise. This is important as augmented blood pressure responses during exercise put individuals at greater risk for development of cardiovascular disease.

Water deprivation does not augment sympathetic or pressor responses to sciatic afferent nerve stimulation in rats or to static exercise in humans.

Excess dietary salt intake excites central sympathetic networks, which may be related to plasma hypernatremia. Plasma hypernatremia also occurs following water deprivation (WD). The purpose of this study was to test the hypothesis that WD induces hypernatremia and consequently augments sympathetic and pressor responses to sympathoexcitatory stimuli in rats and humans. Sympathetic nerve activity (SNA) and arterial blood pressure (ABP) responses to sciatic afferent nerve stimulation (2-20 Hz) and chemical stimulation of the rostral ventrolateral medulla (RVLM) were assessed in rats after 48 h of WD and compared with normally hydrated control rats (CON). In a parallel randomized-crossover human experiment (n = 13 healthy young adults), sympathetic (microneurography) and pressor (photoplethysmography) responses to static exercise were compared between 16-h WD and CON conditions. In rats, plasma [Na+] was significantly higher in WD versus CON [136 ± 2 vs. 144 ± 2 (SD) mM, P < 0.01], but sciatic afferent nerve stimulation produced similar increases in renal SNA [5 Hz, 174 ± 34 vs. 169 ± 49% (SD), n = 6-8] and mean ABP [5 Hz, 21 ± 6 vs. 18 ± 7 (SD mmHg, n = 6-8]. RVLM injection of l-glutamate also produced similar increases in SNA and ABP in WD versus CON rats. In humans, WD increased serum [Na+] [140.6 ± 2.1 vs. 142.1 ± 1.9 mM (SD), P = 0.02] but did not augment sympathetic [muscle SNA: change from baseline (Δ) 6 ± 7 vs. 5 ± 7 (SD) bursts/min, P = 0.83] or mean ABP [Δ 12 ± 5 vs. 11 ± 8 (SD) mmHg, P = 0.73; WD vs. CON for all results] responses during the final minute of exercise. These findings suggest that despite eliciting relative hypernatremia, WD does not augment sympathetic or pressor responses to sciatic afferent stimulation in rats or to static exercise in humans. NEW & NOTEWORTHY Excess dietary salt intake excites central sympathetic networks, which may be related to plasma hypernatremia. Plasma hypernatremia also occurs following water deprivation (WD). We sought to determine whether plasma hypernatremia/hyperosmolality induced by WD augments sympathetic and pressor responses to sympathoexcitatory stimuli. Our findings suggest that WD does not augment sympathetic or pressor responses to sciatic afferent nerve stimulation in rats or to static exercise in humans.