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Background: High dietary sodium intake may induce a small, yet physiologically relevant rise in serum sodium concentration, which associates with increased systolic blood pressure. Cellular data suggest that this association is mediated by increased endothelial cell stiffness. We hypothesized that higher serum sodium levels were associated with greater arterial stiffness in participants in the Systolic Blood Pressure Intervention Trial (SPRINT)., Methods: Multivariable linear regression was used to examine the association between baseline serum sodium level and (i) pulse pressure (PP; n = 8,813; a surrogate measure of arterial stiffness) and (ii) carotid-femoral pulse wave velocity (CFPWV; n = 591 in an ancillary study to SPRINT)., Results: Baseline mean ± SD age was 68 ± 9 years and serum sodium level was 140 ± 2 mmol/L. In the PP analysis, higher serum sodium was associated with increased baseline PP in the fully adjusted model (tertile 3 [≥141 mmol] vs. tertile 2 [139-140 mmol]; β = 0.87, 95% CI = 0.32 to 1.43). Results were similar in those with and without chronic kidney disease. In the ancillary study, higher baseline serum sodium was not associated with increased baseline CFPWV in the fully adjusted model (β = 0.35, 95% CI = -0.14 to 0.84)., Conclusions: Among adults at high risk for cardiovascular events but free from diabetes, higher serum sodium was independently associated with baseline arterial stiffness in SPRINT, as measured by PP, but not by CFPWV. These results suggest that high serum sodium may be a marker of risk for increased PP, a surrogate index of arterial stiffness., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Sympathetic activity and renal norepinephrine spillover are increased in obese individuals. We have reported that infusion of nonesterified fatty acids increases blood pressure in animals through stimulation of the sympathetic nervous system., Methods: In this study, we assessed the effect of increasing circulating nonesterified fatty acids on systemic and renal norepinephrine kinetics in healthy adults by infusing fat emulsion and heparin for 4 h. (3)H-norepinephrine was infused for 60 min before and again during the last hour of the fatty acid infusion to assess norepinephrine kinetics. Renal venous blood samples were obtained to calculate renal norepinephrine spillover., Results: Nonesterified fatty acid levels increased threefold during the first hour and remained elevated throughout the study. Arterial and renal venous plasma norepinephrine levels fell by 15% and 20%, respectively, during the infusion (P < .05 for both). Kinetic analysis indicated that systemic release of norepinephrine into an extravascular compartment decreased from 11.6 +/- 1.1 to 10.0 +/- 1.3 nmol/min/m(2) (P = .067) and renal venous norepinephrine spillover decreased from 454 +/- 54 pmol/min (P = .055)., Conclusions: These results indicate that nonesterified fatty acids do not have a direct stimulating effect on whole-body or renal sympathetic activity. It is possible that increased plasma levels of fatty acids serve as a signal to decrease sympathetic tone during the fasting state.

Background: Individuals differ in their blood pressure (BP) response to changes in dietary sodium (Na+) intake. It is possible that differences in BP responses to dietary Na+ are influenced by genes., Methods: A total of 35 older (62.9 +/- 1.2 years) hypertensive subjects had their mean arterial blood pressure (MABP) determined after 8 days of low (20 mmol/day) and high (200 mmol/day) Na+ intake. The insertion/ deletion polymorphism of the angiotensin converting enzyme (ACE) gene was genotyped with standard polymerase chain reaction methods., Results: Of the 35 subjects, 24 were classified as sodium-sensitive (> or = 5 mm Hg increase in MABP in response to the increase in dietary Na+) and 11 were classified as sodium-resistant (<5 mm Hg increase in MABP). Those homozygous for the insertion allele of the ACE gene (insertion/insertion [II]; n = 8) had lower (P = .04) MABP responses to the increase in dietary Na+ (0 +/- 3 mm Hg) compared to heterozygotes (insertion/deletion [ID]; n = 20) (9 +/- 2 mm Hg; P = .0001) and those homozygous for the deletion allele (deletion/deletion [DD]; n = 7) (9 +/- 3 mm Hg; P = .05). The prevalence of sodium sensitivity was higher (P = .0083) in DD (71%) and ID (83%) compared to II (25%) genotype groups., Conclusions: Based on these data in older hypertensive individuals, we conclude that the ACE gene ID and DD genotypes are associated with an increase in BP during a high Na+ diet, which is consistent with the phenotypic characteristic of sodium sensitivity.

The majority of older hypertensive humans are sodium sensitive and they are characterized by increased alpha-adrenergic responsiveness relative to their level of sympathetic nervous system (SNS) activity. To test the hypothesis that heightened SNS activity and/or increased alpha-adrenergic receptor responsiveness during sodium loading may play a role in the sodium-dependent increase in blood pressure in older sodium-sensitive hypertensives, we used compartmental analysis of [3H]norepinephrine (NE) kinetics to determine the release rate of NE into an extravascular compartment (NE2) as an index of systemic SNS activity and determined forearm blood flow responses to graded intrabrachial artery NE and angiotensin II (ANG II) infusions and platelet membrane alpha2-receptor properties in 24 older (age 64 +/- 7 years) hypertensive subjects. Subjects were studied at the end of 1 week of a low (20 mmol/day)- and again at the end of 1 week of a high (200 mmol/day)-sodium diet. Subjects were categorized as sodium sensitive (SS) if they had a > or = 5 mm Hg increase in mean arterial blood pressure (MABP) with dietary sodium loading (n = 16), or sodium-resistant (SR) if their MABP increased by < 5 mm Hg (n = 8). Neither dietary sodium intake nor sodium-sensitivity status significantly affected arterial plasma NE levels, NE2, or other NE kinetic parameters. Forearm blood flow responses to NE or to ANG II, and platelet alpha2-receptor properties were similar between the SS and SR groups. These results suggest that the sodium-dependent increase in MABP that characterizes SS hypertension among older humans is not because of an increase in systemic SNS activity or increased arterial adrenergic receptor responsiveness.