Stress-induced Pressure Natriuresis Research Articles

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.

Abstract P642: Impact of Urinary Endothelin-1 on Derangements in Stress-Induced Pressure Natriuresis

Sodium retention during stress (retainer) is known to increase the risk of hypertension and other diseases. Our group has previously shown that angiotensin II type I receptor blockade improves natriuresis in retainers. Since our pre-clinical studies demonstrate that angiotensin II inhibits endothelin-1 (ET-1) dependent natriuresis, we predict that ET-1 may be linked to the response. We hypothesize that reduction in urinary (renal) ET-1 accounts for derangements in sodium handling under stress, a link never before explored in a large human cohort. We evaluated urinary ET-1 and albumin excretion in 4 studies of stress-induced pressure natriuresis, of which 3 were observational studies with 776 healthy youth (15 - 19 years) enrolled in a 5 hr protocol (1 hr of mental stress before and after 2 hrs of rest). The 4th study involved 213 African American adults (18 - 54 years) in a double blind crossover trial comparing irbesartan (angiotensin II type I receptor antagonist) to placebo. The protocol entailed 7 days of vehicle (placebo or irbesartan 150 mg P.O.) followed by a 3 hr protocol (1 hr of rest before and after 1 hr of mental stress). In all studies, 60 min urine samples were obtained. Subjects were grouped as retainers or excreters if they retained or excreted sodium under stress. In the observational studies, mean change in ET-1 between stress and baseline was significant (p&lt;0.001), being negative (mean= -0.0154 pmol/min) in retainers but positive (mean= 0.0194 pmol/min) in excreters. ET-1 excretion was significantly higher (p&lt;0.028) in retainers than excreters at baseline but significantly lower in retainers under stress (p&lt;0.0001). ET-1 excretion continued to decline in retainers during recovery but returned to pre-stress levels in excreters. Albumin excretion and albumin to creatinine ratio were significantly higher in retainers (p&lt;0.046, p&lt;0.008, respectively). During stress, the irbesartan group had significantly higher ET-1 excretion than placebo (p&lt;0.001). Thus loss of ET-1-dependent natriuresis may account for sodium retention during stress and correction of sodium handling re-establishes ET-1-mediated natriuresis. Retainers have both lower ET-1 excretion and increased albuminuria, suggesting renal impairment and risk for future diseases.

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 Excretion

Impaired stress-induced pressure natriuresis, ie, an inadequate compensatory increase in urinary sodium excretion (U(Na)V) in response to a stress-induced blood pressure increase, may lead to the premature development of essential hypertension. To assess the heritability of baseline U(Na)V, stress U(Na)V, and the U(Na)V response to stress (Delta U(Na)V=stress U(Na)V- baseline U(Na)V), we studied 396 black and 494 white twins, including monozygotic and dizygotic twins of the same as well as the opposite sex (mean age: 17.6+/-3.3 years; range: 11.9 to 30.0 years). Bivariate genetic model fitting was performed to examine the extent to which genetic and environmental factors are common or specific to baseline and stress U(Na)V. Heritability estimates for Delta U(Na)V can be derived from these bivariate models. All of the bivariate analyses were performed separately in whites and blacks, because univariate models for baseline U(Na)V showed significant ethnic differences in heritability estimates. Best-fitting models showed that the heritability of stress U(Na)V was 0.42 in whites and 0.58 in blacks. Only 15% and 11% of the total variance could be attributed to genetic factors common to baseline and stress U(Na)V in whites and blacks, respectively. After removal of all of the shared influences with baseline U(Na)V, heritabilities for stress U(Na)V were 0.32 in whites and 0.57 in blacks. Heritability estimates for Delta U(Na)V were 0.36 in whites and 0.39 in blacks. In summary, this study establishes Delta U(Na)V and stress U(Na)V as heritable phenotypes that may be used to study the genetic etiology of early hypertension development.

Relationship of body composition to stress-induced pressure natriuresis in youth

The contribution of stress to obesity-related cardiovascular disease is uncertain. The purpose of this study was to examine the influence of body composition on stress-induced pressure natriuresis. Dual energy x-ray absorptiometry was performed in 127 African American and white youths to assess lean body mass (LBM), fat mass (FM), and total percentage of body fat (%BF). The stress protocol was comprised of a 2-h baseline period, 1-h video game competition stressor, and 2-h recovery period. Blood and urine samples were collected hourly and blood pressure (BP) was obtained at 15-min intervals. Both BP and urinary sodium excretion(U(Na)V) increased from baseline to stress and returned to prestress levels after stress (P = .001 for each). The BP levels and changes were positively correlated with LBM. In contrast, levels and changes in sodium excretion U(Na)V were inversely correlated with FM and %BM. Multiple regression analyses that included ethnicity, sex, angiotensin II (Ang II), and measures of body composition in the models indicated the following: a) LBM was the best predictor of stress systolic BP and independently contributed with ethnicity to stress diastolic BP; b) ethnicity was the only independent predictor of the stress-related change in systolic and diastolic BP; c) LBM was the only independent predictor of the change in BP from stress to recovery for both systolic and diastolic BP; and d) total percent body fat accounted for 11.2% of the variance of stress U(Na)V, with Ang II contributing an additional 6.1%. Based on the results of this study, ethnicity and body composition are related to stress-induced pressure natriuresis.

More on the sodium saga.

The relationship between sodium (salt) intake and blood pressure has been convincingly established by epidemiological, observational, interventional, physiological, and some genetic evidence for some time. Yet the interaction remains the subject of passionate and heated debate. Even among those who are convinced of the salt–blood pressure interaction, some advocate a population-wide attempt to reduce dietary salt intake, arguing on the basis of epidemiological and interventional evidence, and others who suggest that such interventions should be targeted toward those most likely to benefit: the “salt-sensitive” subpopulation. Studies have characterized such subgroups on the basis of higher blood pressure, increased age or African-American ethnicity.1 The issue is rendered even more compelling by the findings that salt sensitivity can be identified among “normotensive” subjects (ie, those with blood pressure <140/90) as well as those with hypertension1 and the designation of those with blood pressure levels between 120 and 139 mm Hg systolic and 80 and 89 diastolic as prehypertensive2 and at increased risk for development of fixed hypertension and for cardiovascular events compared with those with lower blood pressure.3 Observational data have provided a starting point for the quantitative considerations of dietary salt intake. The most recent (1999–2000) NHANES survey provides an estimated dietary sodium intake based on food records, excluding discretionary sodium, of 135 to 204 mmol per day for men and 100 to 135 mmol per day for women in the United States.4 Questionnaires are acknowledged to underestimate actual intake, and urinary sodium excretion has been shown to provide a more accurate index of total sodium intake because it represents ≈93% of intake at steady-state conditions.5 A recent British survey reported that urinary sodium excretion averaged 187 mmol per day for men and 139 mmol per day for women.5 This was very similar to …

Race differences in stress-induced pressure natriuresis and left ventricular geometry

OR-41 Key Words: Race, Pressure Natriuresis, LV Geometry

Adiposity is related to gender differences in impaired stress-induced pressure natriuresis.

The purpose of this study was to determine if there are gender differences in stress-induced pressure natriuresis and to examine the effects of adiposity on these differences. The subjects were 151 boys and 141 girls 15 to 18 years of age who underwent a 5-hour stress protocol (2-hour prestress, 1-hour stress, 2-hour poststress) after being brought into similar levels of sodium balance. The gender-by-condition interaction was significant for systolic and diastolic blood pressure (P=0.001 for both), and the effect of condition was significant for sodium excretion (P=0.001). Systolic blood pressure was higher for boys throughout the protocol (P=0.001 for each) and correlated with body mass index at each condition (range in r=0.28 to 0.35; P<0.001 for each). Hemodynamically, in boys body mass index was correlated with cardiac output during stress (r=0.23; P=0.006), which was correlated with systolic blood pressure (r=0.21; P=0.01). With respect to natriuresis, body mass index was inversely correlated with sodium excretion during stress (r=-0.22; P=0.008) and positively correlated with angiotensin II in a subsample of boys (n=89: r=0.31; P=0.003). The inverse correlation between angiotensin II and sodium excretion during stress approached significance (r=-0.17; P<0.06). Similar results were not observed for girls. In conclusion, gender differences in stress-induced pressure natriuresis appear to be related to the influence of adiposity on both blood pressure and natriuresis.

Fat impairs stress-induced pressure natriuresis in African-American boys

Fat impairs stress-induced pressure natriuresis in African-American boys

Lean body mass facilitates stress-induced pressure natriuresis in African-American youth

Lean body mass facilitates stress-induced pressure natriuresis in African-American youth

Impaired stress-induced pressure natriuresis increases cardiovascularload in African American youths

Background We hypothesized that impaired stress-induced pressure natriuresis increases blood pressure (BP) load. Methods The 118 African American youths were brought into similar levels of sodium balance. The protocol consisted of a 2-h baseline period, a 1-h stress period (competitive video games), and a 2-h recovery period. Results: Normal pressure natriuresis ( n = 80) resulted from a resistance-mediated (r = 0.23; P < .03) increase in BP ( P < .001). In contrast, impaired pressure natriuresis ( n = 38), leading to an extended period of elevated BP ( P < .05), resulted from a volume-mediated (r = 0.55; P < .002) increase in BP ( P < .001). Conclusions: Impaired stress-induced pressure natriuresis may contribute to the development of essential hypertension, particularly in African Americans.

Impaired Stress-Induced Pressure Natriuresis Is Related to Left Ventricle Structure in Blacks

The mechanisms through which stress may contribute to the racial difference in the prevalence of essential hypertension and associated target organ damage remain unclear. This study examined differences in stress-induced pressure natriuresis in 69 black and 52 white normotensives age 14 to 27 years, all with a positive family history of hypertension. Urine samples for sodium excretion were collected before and after a series of tasks (video game challenge, forehead cold stimulation). The average blood pressure across the 2 tasks and the average increase in blood pressure to the 2 tasks were calculated. Blacks had higher mean systolic (131+/-12 versus 126+/-12 mm Hg, P<0.02) and diastolic (77+/-8 versus 72+/-9 mm Hg, P<0.001) blood pressure and a greater average change in systolic blood pressure (15+/-9 versus 11+/-7 mm Hg, P<0.04). This was associated with a smaller change in sodium excretion (2+/-6 versus 7+/-10 mEq/h, P<0.002). The change in sodium excretion was related to the change in systolic (r=0.31, P<0.03) and diastolic (r=0.27, P<0.05) blood pressure in whites but not in blacks. Relative wall thickness was greater in blacks (0.31+/-0.04 versus 0.29+/-0.03, P<0.002). In conclusion, impaired stress-induced pressure natriuresis in blacks may contribute to racial differences in essential hypertension and its sequelae.

Sex differences in stress induced pressure natriuresis in African-American youths

Sex differences in stress induced pressure natriuresis in African-American youths