Angiotensin II and the Natriuretic and Blood Pressure Response to Mental Stress in African Americans.

Objective: To test the hypothesis that Angiotensin II (Ang II) is a contributing factor to the response pattern in African Americans (AAs) who retain rather than excrete sodium during mental stress. Design/Study Participants: Double-blind, randomized, cross-over trial of 87 healthy AAs aged 18 to 50 years. Interventions: The study participants received either a placebo or irbesartan, (150 mg PO), an Ang II receptor antagonist, for seven days prior to stress testing. Urinary sodium excretion (UNaV) and systolic blood pressure (SBP) were collected prior to and throughout a mental stress protocol (rest and stress period). Setting: A southeastern university. Main Outcome Measures: Ang II, SBP, and sodium retention. Results: During the placebo condition, 62 participants showed the expected increase in UNaV (excreters) while 25 participants reduced UNaV during stress (retainers). Irbesartan retainers demonstrated a reversal in the direction of their natriuretic response, now increasing UNaV in response to stress (∆ UNaV of -.094 mmol/min with placebo vs .052 mmol/min on irbesartan; P<.001). In excreters, irbesartan reduced SBP levels during both rest (-2.36 mm Hg; P=.03) and stress (-4.59;P<.0001), and an even more pronounced reduction in SBP was demonstrated by retainers on treatment during both rest (-4.29 mm Hg; P=.03) and stress (-6.12; P<.001). Conclusions: Ang II contributes to sodium retention in retainers. Furthermore, our findings indicate that suppression of Ang II has a beneficial effect on SBP during rest and stress in this population.

Adverse childhood experiences and blood pressure trajectories from childhood to young adulthood: the Georgia stress and Heart study.

BACKGROUND: The purposes of this study were to assess the long-term effect of adverse childhood experiences (ACEs) on blood pressure (BP) trajectories from childhood to young adulthood and to examine whether this relation is explained by childhood socioeconomic status (SES) or risk behaviors that are associated with ACEs. METHODS AND RESULTS: Systolic and diastolic BPs were measured up to 16 times (13 times on average) over a 23-year period in 213 African Americans and 181 European Americans 5 to 38 years of age. Retrospective data on traumatic experiences before 18 years of age were collected, including abuse, neglect, and household dysfunction. Individual growth curve modeling within a multilevel framework was used to examine the relation between exposure to ACEs and BP development. No main effect of ACEs on average BP levels was found. However, a significant interaction of ACE score with age(3) was observed (systolic BP, P=0.033; diastolic BP, P=0.017). Subjects who experienced multiple traumatic events during childhood showed a faster rise in BP levels after 30 years of age than those without ACEs. As expected, a graded association of ACEs with childhood socioeconomic status and negative health behaviors was observed (P<0.001). The ACE-systolic BP relation was not explained by these factors, whereas the ACE-diastolic BP relation was partially mediated by illicit drug use. CONCLUSION: In this novel longitudinal study, we observed that participants who were exposed to multiple ACEs displayed a greater increase in BP levels in young adulthood compared with their counterparts without ACEs.

Stress and salt sensitivity in primary hypertension.

As the development of hypertension and target organ damage becomes more prevalent, it becomes exceedingly important to determine the underlying mechanisms through which this detrimental development occurs. Specifically, our studies and others have explored mechanisms through which stress elicits a salt-sensitive response in approximately 20-30 % of the population, resulting in the early development of hypertension and target organ damage. Data associated with this stress-induced cardiovascular response pattern have recently demonstrated additional effects across the body systems including factors contributing to the development of osteoporosis, obesity, autoimmune disease, and chronic inflammation. As each of these diseases become more prevalent in conjunction with hypertension, further research may discover stress and salt sensitivity to be at the "heart" of the matter for the development of many of today's most deadly conditions.

A genome-wide methylation study of severe vitamin D deficiency in African American adolescents.

OBJECTIVES: To test the hypothesis that changes in DNA methylation are involved in vitamin D deficiency-related immune cell regulation using an unbiased genome-wide approach combined with a genomic and epigenomic integrative approach. STUDY DESIGN: We performed a genome-wide methylation scan using the Illumina HumanMethylation 27 BeadChip on leukocyte DNA of 11 cases of vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] ≤ 25 nmol/L) and 11 age-matched controls ([25(OH)D] > 75 nmol/L); the subjects were African American normal-weight (body mass index <85th percentile) males aged 14-19 years. The Limma package was used to analyze each CpG site for differential methylation between cases and controls. To correct for multiple testing, the set of raw P values were converted to false discovery rates (FDRs). We also compared our findings with the recent data from Genome-Wide Association Studies of circulating 25(OH)D levels and then performed a permutation test to examine whether the "double hit" genes were randomly enriched. RESULTS: A total of 79 CpG sites achieved raw P < .001. Of the 79 CpG sites, 2 CpG sites survived multiple testing: cg16317961 (raw P = 3.5 × 10(-6), FDR = 0.078, in MAPRE2) and cg04623955 (raw P = 5.9 × 10(-6), FDR = 0.078, in DIO3). Furthermore, 3 out of the 4 genes previously identified in the 2 Genome-Wide Association Studies were also significant at the methylation level (DHCR7: cg07487535, P = .015 and cg10763288, P = .017; CYP2R1: cg25454890, P = .040; CYP24A1: cg18956481, P = .022), reflecting significant enrichment (P = .0098). CONCLUSION: Severe vitamin D deficiency is associated with methylation changes in leukocyte DNA. The genomic and epigenomic approach reinforce the crucial roles played by the DHCR7, CYP2R1, and CYP24A1 genes in vitamin D metabolism.

Aldosterone contributes to elevated left ventricular mass in black boys.

BACKGROUND: Left ventricular hypertrophy (LVH) poses a great risk of cardiovascular morbidity and mortality in adults and may pose a serious risk in children. Adult studies have shown that renin-angiotensin-aldosterone system (RAAS) levels directly correlate with left ventricular mass index (LVMI). The purpose of this study is to explore race- and sex-related effects of the RAAS on LVMI in adolescents. METHODS: Data were collected from a sample of 89 blacks (44 girls, 45 boys) and 102 whites (40 girls, 62 boys) aged 15-19. Data collected included sex, age, body mass index (BMI), LVMI, baseline blood pressure, and levels of aldosterone and angiotensin II. RESULTS: In black males, increased aldosterone levels correlated with decreased sodium excretion (r= -0.336, p=0.024), increased blood pressure (r=0.358, p=0.016), and increased LVMI (r=0.342, p=0.022). In black females, increased aldosterone levels correlated with increased baseline blood pressure (r=0.356, p=0.018). In white males, increased aldosterone correlated with decreased sodium excretion (r= -0.391, p=0.002). In white females, aldosterone levels correlated with increased baseline blood pressure (r=0.323, p=0.042) and decreased sodium excretion (r= -0.342, p=0.031). CONCLUSIONS: The results suggest the following model in black males: increased aldosterone leads to increased sodium retention, causing a volume-mediated increase in blood pressure; increased blood pressure results in increased left ventricular mass, and eventually LVH.

α-Adrenergic receptor blockade attenuates pressor response during mental stress in young black adults.

Black individuals exhibit increased blood pressure (BP) responses to sympathetic stimulation that are associated with an increased risk of hypertension (HTN). We tested the hypothesis that α1 -adrenergic blockade inhibits the increased BP response during and after 45-min stress in young normotensive Black adults, which may be mediated, in part, by dampened vasoconstriction and decreased renal sodium retention. Utilizing a double-masked randomized, crossover study design, 51 normotensive Black adults (31 ± 8 yr) were treated with either a placebo or 1 mg/day of prazosin for 1 week. On the final day of each treatment, hemodynamic measures and urinary sodium excretion (UNaV) were collected before (Rest), during (Stress) and after (Recovery) 45 min of mental stress induced via a competitive video game task. During the Stress period, diastolic BP and total peripheral resistance (TPR) were significantly lower with prazosin compared to placebo (p < .05 for both). Similarly, we observed lower systolic BP, diastolic BP, and TPR during the Recovery period with prazosin versus placebo (p < .05 for both). There was no effect of prazosin on stress-associated UNaV. The change in systolic BP from Rest to Recovery was positively associated with the change in TPR with both treatments (p < .05 for both). In summary, prazosin treatment dampened BP reactivity to 45-min mental stress and lowered post-stress BP over the recovery period, which was linked to reduce TPR in young normotensive Black adults. These results suggest that α1 -adrenergic receptor activity may contribute to BP responses and delayed BP recovery to prolonged mental stress through increased vasoconstriction in Black adults.

Association between serum 25-hydroxyvitamin D and the effects of Angiotensin II receptor blocker on renal function among African Americans: A post hoc analysis of a randomized placebo-controlled trial.

We tested the hypothesis that vitamin D status may modify the effect of Angiotensin II receptor blocker (ARB) on renal function among African Americans. Sixty-four participants were included in this ancillary study from a randomized, double-blind, placebo-controlled, crossover trial among normotensive African Americans to test the effect of ARB on stress response of blood pressure and renal sodium handling. The participants were randomly assigned to receive either ARB or placebo for one week, washed out for one week and then cross-overed to receive the other intervention for one week. On the final day of each intervention, the participant underwent a mental stress test. Baseline serum 25-hydroxyvitamin D [25(OH)D] level was measured in this ancillary study. Sixty-four participants were included, aged 26.5 ± 10.2 years and 47% were female. Among the participants with the serum 25(OH)D concentrations in the low tertile, ARB treatment was associated with 2.58 mg/dL higher blood urea nitrogen (BUN) (P < .001) and was not associated with serum creatinine (SCr) or estimated glomerular filtration rate (eGFR) (Ps > .05). Among the participants in the high 25(OH)D tertile, ARB was associated with 1.59 mg/dL lower BUN (P < .001), 0.08 mg/dL lower SCr (P = .001), and 8.59 mL/min/1.73 m2 higher eGFR (P = .001). The interactions between vitamin D and ARB on renal function were more significant during stress and recovery than at rest. The effects of ARB treatment on renal function are modified by the vitamin D status among African Americans. ARB may improve renal function only among the ones with optimal vitamin D status.

Modest Sodium Reduction Increases Circulating Short-Chain Fatty Acids in Untreated Hypertensives: A Randomized, Double-Blind, Placebo-Controlled Trial.

High-sodium diet may modulate the gut microbiome. Given the circulating short-chain fatty acids (SCFAs) are microbial in origin, we tested the hypothesis that the modest sodium reduction would alter circulating SCFA concentrations among untreated hypertensives, and the changes would be associated with reduced blood pressure and improved cardiovascular phenotypes. A total of 145 participants (42% blacks, 19% Asian, and 34% females) were included from a randomized, double-blind, placebo-controlled cross-over trial of sodium reduction with slow sodium or placebo tablets, each for 6 weeks. Targeted circulating SCFA profiling was performed in paired serum samples, which were collected at the end of each period, so as all outcome measures. Sodium reduction increased all 8 SCFAs, among which the increases in 2-methylbutyrate, butyrate, hexanoate, isobutyrate, and valerate were statistically significant (Ps<0.05). Also, increased SCFAs were associated with decreased blood pressure and improved arterial compliance. There were significant sex differences of SCFAs in response to sodium reduction (Ps<0.05). When stratified by sex, the increases in butyrate, hexanoate, isobutyrate, isovalerate, and valerate were significant in females only (Ps<0.05), not in males (Ps>0.05). In females, changes in isobutyrate, isovalerate, and 2-methylbutyrate were inversely associated with reduced blood pressures (Ps<0.05). Increased valerate was associated with decreased carotid-femoral pulse wave velocity (P=0.040). Our results show that dietary sodium reduction increases circulating SCFAs, supporting that dietary sodium may influence the gut microbiome in humans. There is a sex difference in SCFA response to sodium reduction. Moreover, increased SCFAs are associated with decreased blood pressures and improved arterial compliance. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00152074.

Serum 25-Hydroxyvitamin D Concentrations Are Associated with Mental Health and Psychosocial Stress in Young Adults.

: We aimed to test the hypothesis that serum 25-hydroxyvitamin D3 (25(OH)D) concentration is associated with mental health and life stress measures in young adults and investigate gender and racial disparities in these associations. This study comprised 327 black and white participants. Depression, trait anxiety, perceived stress, and hostility were measured by the following validated instruments: Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), and Cook-Medley Hostility Scale (CMHS). Linear regression was used to estimate correlations between serum 25(OH)D concentration and mental health measurements in the total population and in subgroups stratified by gender and race. In this sample (28.2 ± 3.1 years, 52% female, 53% black), serum 25(OH)D concentration was negatively related to BDI, STAI, PSS, total CMHS score, and the majority of CMHS subscale scores (p-values < 0.05). Stratified by gender, most of these associations remained significant only in women (p-values < 0.05). Stratified by race, higher 25(OH)D concentrations in white participants were significantly related to lower BDI, STAI, PSS, and CMHS-cynicism subscales (p-values < 0.05); 25(OH)D concentrations in the black participants were only inversely associated with CMHS and most CMHS subscales (p-values < 0.05) but not with BDI, STAI, and PSS. We present novel findings of consistent inverse relationships between serum 25(OH)D concentration and various measures of mental health and life stress. Long-term interventional studies are warranted in order to investigate the roles of vitamin D supplementation in the prevention and mitigation of depression, anxiety, and psychological stress in young adults.

Urinary prostasin: a possible biomarker for renal pressure natriuresis in black adolescents.

Prostasin is a membrane-bound/secretive serine protease interacting with aldosterone and the epithelial sodium channel in the kidney. We and others have previously proposed the concept of stress-induced pressure natriuresis (SIPN) where increased urinary sodium excretion (UNaV) is coupled with elevated blood pressure (BP) in response to behavioral stress in normotensive adolescents. This study thus aimed to test the relationship between prostasin and pressure natriuresis using the SIPN model. A cohort of 102 normotensive black adolescents (mean age: 17.0 +/- 1.2 y; 56% females) were placed on a controlled sodium (4000 +/- 200 mg/d) and potassium (2600 +/- 200 mg/d) diet for three days before testing. The SIPN protocol consisted of a 1-h baseline period, a 1-h stress period (competitive video game), and a 1-h recovery period. During the stress period, BP elevation was coupled with an increase in UNaV. Urinary prostasin concentration had more than a 2-fold reduction from baseline (38.4 +/- 32.7 ng/mL) to stress (17.2 +/- 16.0 ng/mL), and further declined during recovery (12.1 +/- 16.2 ng/mL) (p < 0.001). Urinary prostasin was inversely correlated with UNaV during stress (r = -0.43, p = 0.0001), even after being normalized by urinary creatinine. Our data suggest that urinary prostasin could be a novel biomarker and/or mechanism for renal pressure natriuresis in normotensive black adolescents.

Stress-induced sodium retention and hypertension: a review and hypothesis.

Hypertension--an important health problem in industrialized nations--is particularly significant in blacks and obese individuals, in whom it is hypothesized to result from impaired renal sodium regulation. We reviewed studies that identified individuals with impaired sodium regulation by examining the natriuretic response to mental stress. A significant percentage of black and obese individuals retain or have a diminished natriuretic response to mental stress despite increased blood pressure (BP). This contributes a volume component to the normal resistance-mediated BP increase, and BP remains elevated after the stressor ceases until the volume expansion diminishes. The stress exposes these individuals to greater cardiovascular load. This response pattern has been linked to renin-angiotensin-aldosterone system activity, and is associated with premature target-organ damage. Assessing stress-induced sodium retention provides a method to identify patients with impaired sodium regulation without using a dietary protocol that poses adherence difficulties, or complicated laboratory assessments. Furthermore, research using this technique indicates the effectiveness of renin-angiotensin-aldosterone system blockers in correcting impaired sodium regulation and consequent hypertension in these individuals.

Views of hypertension among young African Americans who vary in their risk of developing hypertension.

OBJECTIVES: To describe beliefs about hypertension and health education of young African American adults varying in their hypertension risk status. DESIGN: Fifty-eight African American young adults (17-20 years) were selected based on low and high risk criteria for hypertension assessed in earlier investigations of hemodynamic responses to stress. The sample included 15 high risk males, 13 low risk males, 14 high risk females, and 16 low risk females who were interviewed indepth about their hypertension beliefs and health education experiences. Variable-based matrices identified participants with similar responses. RESULTS: Overall, participants had a limited understanding of hypertension. For example, they linked the condition to eating a diet high in pork and fat and having a positive family history of hypertension with little acknowledgement of weight, smoking, race and sex as key contributors to hypertension onset. Distinctions were found between risk categories and along sex lines. Most high risk participants believed stress could cause hypertension. High risk females believed that they were at risk for developing hypertension but lacked prevention strategies. High risk males were generally uninformed about risk or prevention. More low risk females believed in prevention compared to few low risk males. Participants reported little formal health education about hypertension and recommended that hypertension education be improved through more effective and relevant approaches in high school health education classes. CONCLUSIONS: These findings support the need for comprehensive and revitalized hypertension prevention programs for young African Americans. Participant views varied with hypertension risk status and gender suggesting that targeted educational efforts should reflect these differences.

Sodium Reduction, Metabolomic Profiling, and Cardiovascular Disease Risk in Untreated Black Hypertensives.

Dietary sodium restriction has multiple beneficial effects on cardiovascular health. The underlying mechanisms are not fully understood, and the roles of metabolomics have been rarely studied. We aimed to test the hypothesis that the reduction in dietary sodium intake would induce changes in metabolomic profiling among black hypertensives, and the changes would be associated with reduced blood pressure (BP) and improved skin capillary density. A total of 64 untreated black hypertensives were included from a randomized, double-blind, placebo-controlled cross-over trial of sodium reduction. The participants were given either 9 slow sodium tablets (10 mmol sodium per tablet) or placebo tablets daily for 6 weeks, they then crossed over to receive the other tablets for another 6 weeks, while on reduced sodium diet aiming at achieving daily sodium intake around 2.0 g. Untargeted metabolomic profiling was performed in paired serum samples, which were collected at the end of each period, so were BP and capillary density. Mixed-effects models were used. There were 34 metabolites identified with raw P's<0.05. Among those, 2 metabolites including ß-hydroxyisovalerate and methionine sulfone were significantly increased with sodium reduction (false discovery rate =0.006 and 0.099, respectively). Increased ß-hydroxyisovalerate was associated with reduced office systolic BP and ambulatory daytime systolic BP, whereas increased methionine sulfone was associated with reduced 24-hour diastolic BP, ambulatory nighttime diastolic BP, and increased skin capillary density. Our results suggest that dietary sodium reduction increases the circulating levels of ß-hydroxyisovalerate and methionine sulfone. Further studies are warranted. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00152074.

Ethnic Differences in Nighttime Melatonin and Nighttime Blood Pressure: A Study in European Americans and African Americans.

BACKGROUND: Ethnic differences in nighttime blood pressure (BP) have long been documented with African Americans (AAs) having higher BP than European Americans (EAs). At present, lower nighttime melatonin, a key regulator of circadian rhythms, has been associated with higher nighttime BP levels in EAs. This study sought to test the hypothesis that AAs have lower nighttime melatonin secretion compared with EAs. We also determined if this ethnic difference in melatonin could partially explain the ethnic difference in nighttime BP. METHODS: A total of 150 young adults (71 AA; 46% females; mean age: 27.7 years) enrolled in the Georgia Stress and Heart study provided an overnight urine sample for the measurement of 6-sulfatoxymelatonin, a major metabolite of melatonin. Urine melatonin excretion (UME) was calculated as the ratio between 6-sulfatoxymelatonin concentration and creatinine concentration. Twenty-four-hour ambulatory BP was assessed and nighttime systolic BP (SBP) was used as a major index of BP regulation. RESULTS: After adjustment of age, sex, body mass index, and smoking, AAs had significantly lower UME (P = 0.002) and higher nighttime SBP than EAs (P = 0.036). Lower UME was significantly associated with higher nighttime SBP and this relationship did not depend on ethnicity. The ethnicity difference in nighttime SBP was significantly attenuated after adding UME into the model (P = 0.163). CONCLUSION: This study is the first to document the ethnic difference in nighttime melatonin excretion, demonstrating that AAs have lower melatonin secretion compared with EAs. Furthermore, the ethnic difference in nighttime melatonin can partially account for the established ethnic difference in nighttime SBP.

Change of genetic determinants of left ventricular structure in adolescence: longitudinal evidence from the Georgia cardiovascular twin study.

BACKGROUND: Genetic contribution to left ventricular (LV) structure is generally recognized, but whether and how this influence varies by ethnicity or with age is unknown. METHODS: Participants were 517 European-American (EA) and African-American (AA) twin pairs (mean age: 14.6 +/- 3.0) at visit 1 and 422 EA and AA twin pairs at follow-up 4.1 years later. Echocardiograms were obtained on both visits. Data were analyzed using the structural equation modeling software Mx. RESULTS: Body mass index (BMI) was a strong predictor for all LV measures at both visits 1 and 2, accounting for 3.5-24.2% of the total variance. Hemodynamics explained up to 4.5% additional LV measures variance. After adjusting for BMI, LV measures showed substantial heritability (range: 21-71%). Best-fitting longitudinal models revealed considerable novel genetic effects on the interventricular septum, posterior wall-, and relative wall thickness (RWT) (but not LV internal diameter), accounting for 32-41% of the phenotypic variance at visit 2, with no significant gender and ethnic effects. There was a gender difference for LV mass index in AAs (P < 0.01), with a significant influence of novel genetic effects in males (47%), but not in females. No gender difference was seen in EAs, with 34% of the phenotypic variance at visit 2 attributable to novel genetic effects. CONCLUSIONS: The heritability of cardiac structure and geometry was equally substantial in both AAs and EAs. Significant novel genetic influences were detected for all measures but LV inner diameter and LV mass index in AA females. Further developmental genetic studies are warranted to elucidate the nature of the emerging gene effects during the transition from adolescence to adulthood.

Adhesion molecule polymorphisms and pulse wave velocity in American youth.

BACKGROUND: Our research group recently reported that aorto-radial (radial) and aorto-dorsalis-pedis (foot) pulse wave velocity (PWV) as proxies of arterial stiffness are substantially heritable in healthy youth. This article aimed at uncovering the genetic contributions of adhesion molecules, key members in the inflammatory process, to PWV in these young individuals. METHODS: Radial and foot PWV were noninvasively measured with applanation tonometry in 702 black and white subjects (42% blacks, mean age 17.7 +/- 3.3 years) from the Georgia Cardio vascular Twin Study. Eight functional polymorphisms from genes for E-selectin (SELE), P-selectin (SELP), intercellular adhesion molecules-1 (ICAM1), and vascular cell adhesion molecules-1 (VCAM1) were genotyped. RESULTS: Youth with Ser290Asn or Asn290Asn genotype (SELP) compared to those with Ser290Ser had an increase in both radial and foot PWV (6.61 +/- 0.07 vs. 6.41 +/- 0.05 m/s, p = .026; 7.22 +/- 0.05 vs. 7.04 +/- 0.04 m/s, p = .007). TT homozygotes of rs2244529 (SELP) had higher foot PWV (7.28 +/- 0.07 vs. 7.06 +/- 0.03 m/s, p = .002) than CT heterozygotes and CC homozygotes. There appeared to be a decrease in foot PWV in youth with the 241Arg allele (ICAM1) as compared to those without (6.96 +/- 0.08 vs. 7.14 +/- 0.03 m/s, p = .005). For the Asp693Asp (C to T) polymorphism (VCAM1), CC genotype had higher foot PWV than CT and TT genotypes (7.18 +/- 0.04 vs. 6.95 +/- 0.06 m/s, p < .0001). There was an epistatic interaction between Ser290Asn, Gly241Arg, and Asp693Asp on foot PWV (p = .017), explaining 3.6% variance of the foot PWV. CONCLUSION: Genetic variation of adhesion molecules may be implicated in the development of arterial stiffness. Screening for adhesion molecule polymorphisms may help identify high-risk youth.

Impact of breathing awareness meditation on ambulatory blood pressure and sodium handling in prehypertensive African American adolescents.

OBJECTIVES: This study evaluated the impact of a breathing awareness meditation (BAM) program on ambulatory blood pressure and sodium handling in African American adolescents with high-normal systolic blood pressure (SBP) levels. DESIGN AND METHODS: Following three consecutive days of SBP screenings, 66 eligible ninth graders were randomly assigned by school to either BAM (n = 20) or health education control (n = 46) groups. The BAM group engaged in 10-minute BAM sessions at school and at home each day for three months. Teachers conducted sessions at school during health classes. Before and after the intervention, overnight urine samples were collected, and ambulatory SBP, diastolic blood pressure, and heart rate were recorded periodically for 24 hours. RESULTS: Significant changes before and after the intervention were observed between BAM and control groups for SBP during school hours (-4.7 vs .9 mm Hg, P < .05), SBP at night (-4.8 vs -.6 mm Hg, P < .01), and heart rate during school hours (-6.7 vs -2.3 bpm, P < .02), adjusted for their respective preintervention levels. The overnight urinary sodium excretion rate decreased in the BAM group but increased in the control group (-.3 +/- 4.9 vs 1.1 +/- 4.0 mEq/hour, P < .03). CONCLUSIONS: These findings demonstrate the potential beneficial impact of BAM taught by school health teachers on blood pressure control in the natural environment in African American youth at risk for development of hypertension.

Relation of urinary endothelin-1 to stress-induced pressure natriuresis in healthy adolescents.

We hypothesize that delayed natriuresis during mental stress increases the risk of hypertension and other diseases. Our preclinical studies demonstrate an important role for renal endothelin-1 (ET-1) in regulating sodium excretion. Thus, we predict ET-1 may be linked to the delayed stress response in at-risk individuals. We hypothesize that reduced renal ET-1 accounts for derangements in sodium handling under stress, a link never explored in a large human cohort. We determined urinary ET-1 excretion in three observational studies of changes in sodium excretion during mental stress, in which 776 healthy youth (15-19 years) enrolled in a 5-hour protocol (2 hours of rest before and after 1 hour of mental stress). In all studies, 60-minute urine samples were obtained throughout the protocol. Subjects were grouped as retainers (reduced sodium excretion during stress relative to baseline) or excreters (increased sodium excretion during stress relative to baseline). In excreters, ET-1 excretion was significantly increased from baseline to stress (+0.02 pg/min; P < .001). In contrast, ET-1 excretion was significantly higher (P = .028) in retainers than excreters at baseline but significantly reduced in retainers under stress (-0.02 pg/min; P < .001). ET-1 excretion declined further in retainers during recovery but returned to prestress levels in excreters. Albumin excretion and albumin-to-creatinine ratio were significantly higher in retainers (P = .022, P < .001, respectively). Thus, loss of ET-1-dependent natriuresis may account for sodium retention during stress and may predispose retainers to renal diseases such as hypertension and kidney disease.

Sodium Reduction, miRNA Profiling and CVD Risk in Untreated Hypertensives: a Randomized, Double-Blind, Placebo-Controlled Trial.

Sodium reduction decreases blood pressure (BP) and cardiovascular mortality. However, the underlying molecular mechanisms are not well understood. We tested the hypothesis that reduction of sodium intake would change miRNA expression in hypertensive patients, and those changes would be associated with improved cardiovascular phenotypes. A whole genome RNA sequencing was performed in paired serum samples collected at the end of usual sodium intake and reduced sodium intake periods from 10 (age 56.8 ± 8.9) untreated black male hypertensives, selected from a randomized crossover trial of sodium reduction as the discovery cohort. Validation was carried out by the PCR Serum/Plasma Focus panel profiling in paired samples in all 64 (50% males, age 50.2 ± 9.5) untreated black hypertensives from the same trial. Fifteen respondent miRNAs were identified in the discovery stage. miR-143-3p was replicated. Sodium reduction up-regulated miR-143-3p. The increase in miR-143-3p was associated with the reduction of BP and arterial stiffness and the increase in skin capillary density. In conclusion, dietary sodium reduction alters circulating miRNA expressions, and those miRNA changes are associated with reduced BP and improved arterial compliance in untreated black hypertensives, suggesting that miRNA regulation may be one of the underlying mechanisms that dietary sodium regulates cardiovascular health.

Ethnic and gender differences in ambulatory blood pressure trajectories: results from a 15-year longitudinal study in youth and young adults.

BACKGROUND: Cross-sectional studies demonstrated ethnic and gender differences in ambulatory blood pressure patterns, but little is known about the longitudinal development of these differences. METHODS AND RESULTS: Twenty-four-hour ambulatory blood pressure was measured up to 12 times (5 times on average) over a 15-year period in 312 African Americans (AAs) and 351 European Americans aged 7 to 30 years. Multivariate individual growth curves across age were created for daytime and nighttime blood pressure jointly. For both daytime and nighttime systolic blood pressure (SBP), AAs and males had higher levels (P<0.001) than European Americans and females. Males also showed a greater increase with age (P<0.001) than females. For nighttime SBP, a faster increase of SBP with age (P<0.01) in AAs was additionally observed. The ethnic difference in nighttime SBP levels and its increase with age were significantly larger than in daytime SBP. For daytime and nighttime diastolic blood pressure, AAs had higher levels than European Americans (P<0.001), and this difference was significantly larger at night. From late adolescence onward, males showed a greater increase in diastolic blood pressure with age than females. Ethnic and gender differences persisted after adjustment for height, body mass index, socioeconomic status, and stress-related coping styles. Family history of essential hypertension explained ethnic differences in daytime SBP. CONCLUSIONS: We observed significant ethnic and gender differences in longitudinal trajectories of ambulatory blood pressure in youth and young adults. The blunted nocturnal decline and its exacerbation with age in AAs corroborate and extend findings of cross-sectional studies.