Excessive maternal salt intake gives rise to vasopressin-dependent salt sensitivity of blood pressure in male offspring

2021 ◽  
Vol 150 ◽  
pp. 12-22 ◽  
Author(s):  
Young-Beom Kim ◽  
Won Woo Jung ◽  
Seung Won Lee ◽  
Xiangyan Jin ◽  
Hyung Kyung Kang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
Male Offspring

No Evidence of Racial Disparities in Blood Pressure Salt Sensitivity When Potassium Intake Exceeds Levels Recommended in the US Dietary Guidelines

2021 ◽  
Author(s):  
Theodore W. Kurtz ◽  
Stephen E. DiCarlo ◽  
Michal Pravenec ◽  
R. Curtis Morris
Keyword(s):  
Blood Pressure ◽  
Racial Disparities ◽  
Racial Differences ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
Dietary Guidelines ◽  
Potassium Intake ◽  
Dietary Potassium ◽  
The Us ◽  
The Impact

On average, black individuals are widely believed to be more sensitive than white individuals to blood pressure (BP) effects of changes in salt intake. However, few studies have directly compared the BP effects of changing salt intake in black versus white individuals. In this narrative review, we analyze those studies and note that when potassium intake substantially exceeds the recently recommended US dietary goal of 87 mmol/d, black adults do not appear more sensitive than white adults to BP effects of short-term or long-term increases in salt intake (from an intake ≤ 50 mmol/d up to 150 mmol/d or more). However, with lower potassium intakes, racial differences in salt sensitivity are observed. Mechanistic studies suggest that racial differences in salt sensitivity are related to differences in vascular resistance responses to changes in salt intake mediated by vasodilator and vasoconstrictor pathways. With respect to cause and prevention of racial disparities in salt sensitivity, it is noteworthy that 1) on average, black individuals consume less potassium than white individuals and 2) consuming supplemental potassium bicarbonate, or potassium rich foods can prevent racial disparities in salt-sensitivity. However, the new US Dietary Guidelines reduced the dietary potassium goal well-below the amount associated with preventing racial disparities in salt sensitivity. These observations should motivate research on the impact of the new dietary potassium guidelines on racial disparities in salt sensitivity, the risks and benefits of potassium-containing salt substitutes or supplements, and methods for increasing consumption of foods rich in nutrients that protect against salt-induced hypertension.

scholarly journals Mechanisms of blood pressure salt sensitivity: new insights from mathematical modeling

2017 ◽  
Vol 312 (4) ◽  
pp. R451-R466 ◽  
Author(s):  
John S. Clemmer ◽  
W. Andrew Pruett ◽  
Thomas G. Coleman ◽  
John E. Hall ◽  
Robert L. Hester
Keyword(s):  
Mathematical Modeling ◽  
Blood Pressure ◽  
Salt Intake ◽  
Peripheral Resistance ◽  
Extracellular Fluid ◽  
Physiological Model ◽  
Salt Sensitivity ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Bilateral Renal Artery Stenosis

Mathematical modeling is an important tool for understanding quantitative relationships among components of complex physiological systems and for testing competing hypotheses. We used HumMod, a large physiological model, to test hypotheses of blood pressure (BP) salt sensitivity. Systemic hemodynamics, renal, and neurohormonal responses to chronic changes in salt intake were examined during normal renal function, fixed low or high plasma angiotensin II (ANG II) levels, bilateral renal artery stenosis, increased renal sympathetic nerve activity (RSNA), and decreased nephron numbers. Simulations were run for 4 wk at salt intakes ranging from 30 to 1,000 mmol/day. Reducing functional kidney mass or fixing ANG II increased salt sensitivity. Salt sensitivity, associated with inability of ANG II to respond to changes in salt intake, occurred with smaller changes in renal blood flow but greater changes in glomerular filtration rate, renal sodium reabsorption, and total peripheral resistance (TPR). However, clamping TPR at normal or high levels had no major effect on salt sensitivity. There were no clear relationships between BP salt sensitivity and renal vascular resistance or extracellular fluid volume. Our robust mathematical model of cardiovascular, renal, endocrine, and sympathetic nervous system physiology supports the hypothesis that specific types of kidney dysfunction, associated with impaired regulation of ANG II or increased tubular sodium reabsorption, contribute to BP salt sensitivity. However, increased preglomerular resistance, increased RSNA, or inability to decrease TPR does not appear to influence salt sensitivity. This model provides a platform for testing competing concepts of long-term BP control during changes in salt intake.

scholarly journals Excess maternal salt or fructose intake programmes sex-specific, stress- and fructose-sensitive hypertension in the offspring

2015 ◽  
Vol 115 (4) ◽  
pp. 594-604 ◽  
Author(s):  
Clint Gray ◽  
Sheila M. Gardiner ◽  
Matthew Elmes ◽  
David S. Gardner
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Salt Intake ◽  
Maternal Diet ◽  
Cardiovascular Function ◽  
Female Offspring ◽  
Male Offspring ◽  
Pregnant Rats ◽  
Salt Loading ◽  
Male And Female

AbstractThe Western diet is typically high in salt and fructose, which have pressor activity. Maternal diet can affect offspring blood pressure, but the extent to which maternal intake of excess salt and fructose may influence cardiovascular function of the offspring is unknown. We sought to determine the effect of moderate maternal dietary intake of salt and/or fructose on resting and stimulated cardiovascular function of the adult male and female offspring. Pregnant rats were fed purified diets (±4 % salt) and water (±10 % fructose) before and during gestation and through lactation. Male and female offspring were weaned onto standard laboratory chow. From 9 to 14 weeks of age, cardiovascular parameters (basal, circadian and stimulated) were assessed continuously by radiotelemetry. Maternal salt intake rendered opposite-sex siblings with a 25-mmHg difference in blood pressure as adults; male offspring were hypertensive (15 mmHg mean arterial pressure (MAP)) and female offspring were hypotensive (10 mmHg MAP) above and below controls, respectively. Sex differences were unrelated to endothelial nitric oxide activity in vivo, but isolation-induced anxiety revealed a significantly steeper coupling between blood pressure and heart rate in salt-exposed male offspring but not in female offspring. MAP of all offspring was refractory to salt loading but sensitive to subsequent dietary fructose, an effect exacerbated in female offspring from fructose-fed dams. Circadian analyses of pressure in all offspring revealed higher mean set-point for heart rate and relative non-dipping of nocturnal pressure. In conclusion, increased salt and fructose in the maternal diet has lasting effects on offspring cardiovascular function that is sex-dependent and related to the offspring’s stress–response axis.

scholarly journals Activation of the Sympathetic Nervous System Promotes Blood Pressure Salt-Sensitivity in C57BL6/J Mice

Hypertension ◽  
2021 ◽  
Vol 77 (1) ◽  
pp. 158-168
Author(s):  
Ailsa F. Ralph ◽  
Celine Grenier ◽  
Hannah M. Costello ◽  
Kevin Stewart ◽  
Jessica R. Ivy ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
High Salt ◽  
Sodium Balance ◽  
High Salt Diet ◽  
Salt Diet ◽  
High Salt Intake ◽  
Pressure Natriuresis

Global salt intake averages >8 g/person per day, over twice the limit advocated by the American Heart Association. Dietary salt excess leads to hypertension, and this partly mediates its poor health outcomes. In ≈30% of people, the hypertensive response to salt is exaggerated. This salt-sensitivity increases cardiovascular risk. Mechanistic cardiovascular research relies heavily on rodent models and the C57BL6/J mouse is the most widely used reference strain. We examined the effects of high salt intake on blood pressure, renal, and vascular function in the most commonly used and commercially available C57BL6/J mouse strain. Changing from control (0.3% Na + ) to high salt (3% Na + ) diet increased systolic blood pressure in male mice by ≈10 mm Hg within 4 days of dietary switch. This hypertensive response was maintained over the 3-week study period. Returning to control diet gradually reduced blood pressure back to baseline. High-salt diet caused a rapid and sustained downregulation in mRNA encoding renal NHE3 (sodium-hydrogen-exchanger 3) and EnaC (epithelial sodium channel), although we did not observe a suppression in aldosterone until ≈7 days. During the development of salt-sensitivity, the acute pressure natriuresis relationship was augmented and neutral sodium balance was maintained throughout. High-salt diet increased ex vivo sensitivity of the renal artery to phenylephrine and increased urinary excretion of adrenaline, but not noradrenaline. The acute blood pressure–depressor effect of hexamethonium, a ganglionic blocker, was enhanced by high salt. Salt-sensitivity in commercially sourced C57BL6/J mice is attributable to sympathetic overactivity, increased adrenaline, and enhanced vascular sensitivity to alpha-adrenoreceptor activation and not sodium retention or attenuation of the acute pressure natriuresis response.

scholarly journals HIV-positive demonstrate more salt sensitivity and nocturnal non-dipping blood pressure than HIV-negative individuals

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Sepiso K. Masenga ◽  
Annet Kirabo ◽  
Benson M. Hamooya ◽  
Selestine Nzala ◽  
Geoffrey Kwenda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Black People ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
Sub Saharan Africa ◽  
Hiv Positive ◽  
Dietary Salt ◽  
Female Ratio ◽  
Dietary Salt Intake ◽  
Hiv Negative

Abstract Background High dietary salt and a lack of reduced blood pressure (BP) at night (non-dipping) are risk factors for the development of hypertension which may result in end-organ damage and death. The effect of high dietary salt on BP in black people of sub-Saharan Africa living with HIV is not well established. The goal of this study was to explore the associations between salt sensitivity and nocturnal blood pressure dipping according to HIV and hypertension status in a cohort of adult Zambian population. Methods We conducted an interventional study among 43 HIV-positive and 42 HIV-negative adults matched for age and sex. Study participants were instructed to consume a low (4 g) dietary salt intake for a week followed by high (9 g) dietary salt intake for a week. Salt resistance and salt sensitivity were defined by a mean arterial pressure difference of ≤5 mmHg and ≥ 8 mmHg, respectively, between the last day of low and high dietary salt intervention. Nocturnal dipping was defined as a 10–15% decrease in night-time blood pressure measured with an ambulatory blood pressure monitor. Results The median age was 40 years for both the HIV-positive and the HIV-negative group with 1:1 male to female ratio. HIV positive individuals with hypertension exhibited a higher BP sensitivity to salt (95%) and non-dipping BP (86%) prevalence compared with the HIV negative hypertensive (71 and 67%), HIV positive (10 and 24%) and HIV-negative normotensive (29 and 52%) groups, respectively (p < 0.05). Salt sensitivity was associated with non-dipping BP and hypertension in both the HIV-positive and HIV-negative groups even after adjustment in multivariate logistic regression (< 0.001). Conclusions The results of the present study suggest that high dietary salt intake raises blood pressure and worsens nocturnal BP dipping to a greater extent in hypertensive than normotensive individuals and that hypertensive individuals have higher dietary salt intake than their normotensive counterparts. Regarding HIV status, BP of HIV-positive hypertensive patients may be more sensitive to salt intake and demonstrate more non-dipping pattern compared to HIV-negative hypertensive group. However, further studies with a larger sample size are required to validate this.

scholarly journals Salt sensitivity and timed drug therapy in arterial hypertension. Enhancing antihypertensive drug efficacy: a controlled randomised trial

2021 ◽  
Vol 28 (2) ◽  
pp. 46-58
Author(s):  
V. V. Skibitskiy ◽  
V. Yu. Vasil’ev ◽  
A. V. Fendrikova
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Arterial Hypertension ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Salt Intake ◽  
Combined Therapy ◽  
Randomised Trial ◽  
Salt Sensitivity ◽  
Central Blood Pressure

Background. An elevated or inadequate sensitivity to salt intake is an important mechanism for maintaining high blood pressure in patients with arterial hypertension. Chronopharmacotherapy comprises an important approach to control arterial hypertension through personalised correction of blood pressure but requires a further proof of efficacy in salt-sensitive hypertensive patients.Objectives. An assessment of six-month dynamics of diurnal and nocturnal peripheral and central blood pressure in salt-sensitive patients with arterial hypertension under chronopharmacothe­rapy.Methods. A controlled randomised trial included 86 salt-sensitive patients with arterial hypertension. Salt sensitivity was estimated with a Kharchenko’s test. All patients had circadian monitoring of the peripheral and central blood pressure and glomerular filtration rate at baseline and in a six-month follow-up. The patients were randomised into 3 cohorts. Cohort A united patients received perindopril and amlodipine in morning, cohort B — perindopril in morning, amlodipine in evening, cohort C — perindopril in evening, amlodipine in morning. Statistica 12 (StatSoftInc, USA) was used for nonparametric statistical analyses.Results. In six months of chronopharmacotherapy a target arterial pressure was registered in 87.5% patients in cohort A, 96.4 and 96.2% patients in cohorts B and C, respectively. All cohorts exhibited a declining peripheral and central blood pressure over therapy. Cohort A had a greater decline in daytime, and cohorts B and C — both diurnally and nocturnally. Cohorts B and C had more patients with an adequate nocturnal blood pressure decline. Glomerular filtration rate also elevated with perindopril or amlodipine intake before bedtime.Conclusion. The perindopril or amlodipine intake before bedtime in a combined therapy for arterial hypertension provided for a target blood pressure in the overall majority of patients, effectively reduced peripheral and central blood pressure at all time intervals, contributed to optimising the circadian blood pressure profile and increased the glomerular filtration rate.

scholarly journals Molecular Basis of Human Salt Sensitivity: The Role of the 11β-Hydroxysteroid Dehydrogenase Type 2*

1999 ◽  
Vol 84 (10) ◽  
pp. 3745-3749
Author(s):  
Emanuela Lovati ◽  
Paolo Ferrari ◽  
Bernhard Dick ◽  
Kristin Jostarndt ◽  
Brigitte M. Frey ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Microsatellite Marker ◽  
Mineralocorticoid Receptor ◽  
Salt Intake ◽  
Blood Pressure Response ◽  
Salt Sensitivity ◽  
Pressure Response ◽  
Polymorphic Microsatellite Marker ◽  
Polymorphic Microsatellite

Abstract Salt-sensitive subjects (SS) increase their blood pressure with increasing salt intake. Because steroid hormones modulate renal sodium retention, we hypothesize that the activity of the 11β-hydroxy-steroid dehydrogenase type 2 (11βHSD2) enzyme is impaired in SS subjects as compared with salt-resistant (SR) subjects. The 11βHSD2 enzyme inactivates 11-hydroxy steroids in the kidney, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids. We performed an association study using a recently identified single AluI polymorphism in exon 3 and a polymorphic microsatellite marker of the HSD11B2 gene in 149 normotensive white males (37 SS and 112 SR). The activity of the enzyme 11βHSD2 was assessed by determining the urinary ratio of cortisol (THF+5αTHF) to cortisone (THE) metabolites by gas chromatography in all the 37 SS subjects and in 37 age- and body habitus-matched SR volunteers. Mean (THF+5αTHF)/THE ratio was markedly elevated in SS subjects compared with SR subjects (1.51 ± 0.34 vs. 1.08 ± 0.26, P &lt; 0.00001), indicating enhanced access of glucocorticoids to the mineralocorticoid receptor in SS subjects. In 58% of SS subjects this ratio was higher than the maximum levels in SR subjects. The salt-induced elevation in arterial pressure increased with increasing (THF+5αTHF)/THE ratio (r2 = 0.51, P &lt; 0.0001). A total of 12 alleles of the polymorphic microsatellite marker were detected. Homozygosity for the allele A7 was higher in SS subjects than in SR subjects (41 vs. 28%, P &lt; 0.005), whereas the occurrence of the allele A7 with allele A8 was lower in SS subjects than in SR subjects (8 vs. 15%, P&lt; 0.03). The prevalence of salt sensitivity was 35% in subjects with allele A7/A7, whereas salt sensitivity was present in only 9% of the subjects with allele A7/A8. The (THF+5αTHF)/THE ratio was higher in subjects homozygous for the A7 microsatellite allele as compared with the corresponding control subjects. The prevalence of the AluI allele was 8.0% in SR subjects and 5.4% in SS subjects and did not correlate with blood pressure. The decreased activity of the 11βHSD2 in SS subjects indicates that this enzyme is involved in salt-sensitive blood pressure response in humans. The association of a polymorphic microsatellite marker of the gene with a reduced 11βHSD2 activity suggests that variants of the HSD11B2 gene contribute to enhanced blood pressure response to salt in humans.

Abstract MP70: Aldosterone And Inverse Salt Sensitivity Of Blood Pressure

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Peng Xu ◽  
John J Gildea ◽  
Mahabuba Akhter ◽  
Robert M Carey ◽  
Wei Yue ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
High Salt ◽  
Sodium Reabsorption ◽  
High Salt Diet ◽  
Salt Diet ◽  
High Salt Intake ◽  
Low Salt ◽  
Harmful Effects

Salt sensitivity affects approximately 20% of adults worldwide and has similar mortality and morbidity sequalae as hypertension. Research has focused on the harmful effects of a high salt diet but have not focused on the harmful effects of a low salt diet. Inverse salt sensitive (ISS) individuals require high salt intake in order to maintain a normal blood pressure. Aldosterone increases ENaC and sodium reabsorption via the mineralocorticoid receptor (MR). We previously reported that αENaC was significantly lower in ISS renal tubule cells isolated from urine (uRTC), while these cells showed higher ENaC like activities under trypsin stimulation. We hypothesized that aldosterone may act as a stimulus and play a role in ISS high blood pressure on a low salt diet (LSD). Plasma aldosterone was significantly increased on LSD in all salt study participants, and ISS individuals showed the highest aldosterone level (ISS HS 3.8±0.38, n=26; ISS LS 35±3.38, n=22; SR HS 4.34±0.18, n=180; SR LS 32.62±1.6, n=152; SS HS 4.65±0.35, n=43; SS LS 26.08±2.18, n=38; HS Vs LS, p<0.001, two-way ANOVA). Moreover, both aldosterone and plasma renin activity (PRA) were significantly lower in salt sensitive (SS) individuals on LSD (PRA LS: ISS 6.05±0.87, n=17; SR 5.94±0.36, n=108; SS 4.43±0.57, n=34; p<0.05, one-way ANOVA), indicating LSD was protective to SS individuals. Treatment of uRTCs with 1 μM aldosterone increased MR and αENaC expression in ISS but not in SR (salt resistant) cells (MR: SR VEH 12164±213; SR Aldosterone 12327±128; ISS VEH 12128±40 vs ISS Aldosterone 13506±128, n=3, p<0.001, two-way ANOVA; αENaC: SR VEH 5023±46; SR Aldosterone 4895±55; ISS VEH 4270±21 vs ISS Aldosterone 5013±113, n=3, p<0.001, two-way ANOVA). High salt treatment further decreased MR in ISS but not in SR cells (ISS: 142mM 11066±188 vs 192mM 10425±74; p<0.05, n=3 two-way ANOVA). These results are consistent with the hypothesis that ISS individuals retain excess Na + and exhibit decreased BP when compared to SR or SS individuals under high salt diet, but reabsorb more sodium and exhibit elevated blood pressure under low salt diet. Higher circulating aldosterone and ex-vivo urine derived renal cell aldosterone sensitivity under low salt conditions may be a novel diagnostic test to identify ISS individuals.

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