Effects of AT1A receptor deletion on blood pressure  and sodium excretion during altered dietary salt intake

The present study was performed to investigate the role of type 1A ANG II (AT1A) receptors in regulating sodium balance and blood pressure maintenance during chronic dietary sodium variations in AT1A receptor-deficient (−/−) mice. Groups of AT1A (−/−) and wild-type mice were placed on a low (LS)-, normal (NS)-, or high-salt (HS) diet for 3 wk. AT1A(−/−) mice on an LS diet had high urinary volume and low blood pressure despite increased renin and aldosterone levels. On an HS diet, (−/−) mice demonstrated significant diuresis, yet blood pressure increased to levels greater than control littermates. There was no effect of dietary sodium intake on systolic blood pressures in wild-type animals. The pressure-natriuresis relationship in AT1A (−/−) mice demonstrated a shift to the left and a decreased slope compared with wild-type littermates. These studies demonstrate that mice lacking the AT1A receptor have blood pressures sensitive to changes in dietary sodium, marked alterations of the pressure-natriuresis relationship, and compensatory mechanisms capable of maintaining normal sodium balance across a wide range of sodium intakes.

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Sodium Intake and Hypertension

Nutrients ◽

10.3390/nu11091970 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1970 ◽

Cited By ~ 28

Author(s):

Grillo ◽

Salvi ◽

Coruzzi ◽

Salvi ◽

Parati

Keyword(s):

Blood Pressure ◽

Salt Intake ◽

Sodium Intake ◽

Peripheral Resistance ◽

Dietary Sodium ◽

Dietary Salt ◽

High Sodium ◽

Close Relationship ◽

And Function ◽

Modest Reduction

The close relationship between hypertension and dietary sodium intake is widely recognized and supported by several studies. A reduction in dietary sodium not only decreases the blood pressure and the incidence of hypertension, but is also associated with a reduction in morbidity and mortality from cardiovascular diseases. Prolonged modest reduction in salt intake induces a relevant fall in blood pressure in both hypertensive and normotensive individuals, irrespective of sex and ethnic group, with larger falls in systolic blood pressure for larger reductions in dietary salt. The high sodium intake and the increase in blood pressure levels are related to water retention, increase in systemic peripheral resistance, alterations in the endothelial function, changes in the structure and function of large elastic arteries, modification in sympathetic activity, and in the autonomic neuronal modulation of the cardiovascular system. In this review, we have focused on the effects of sodium intake on vascular hemodynamics and their implication in the pathogenesis of hypertension.

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Blood pressure and endocrine responses to changes in dietary sodium intake in cardiac transplant recipients. Implications for the control of sodium balance.

Circulation ◽

10.1161/01.cir.89.3.1153 ◽

1994 ◽

Vol 89 (3) ◽

pp. 1153-1159 ◽

Cited By ~ 25

Author(s):

D R Singer ◽

N D Markandu ◽

M G Buckley ◽

M A Miller ◽

G A Sagnella ◽

...

Keyword(s):

Blood Pressure ◽

Sodium Intake ◽

Dietary Sodium ◽

Sodium Balance ◽

Cardiac Transplant ◽

Transplant Recipients

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Dietary Sodium Restriction in the Management of Chronic Kidney Disease: A Systematic Review and Meta-Analysis of RCTs

10.21203/rs.3.rs-806377/v1 ◽

2021 ◽

Author(s):

Sai Sidharth Manikandan ◽

Murali Dhar

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Salt Intake ◽

Sodium Intake ◽

Meta Analysis ◽

Cost Effective ◽

Mean Difference ◽

Dietary Sodium ◽

High Sodium

Abstract Background: Non-pharmacological strategies such as lowering sodium intake aim to protect renal function and delay the initiation of renal replacement therapy. It might also be a cost-effective method to improve chronic kidney disease (CKD) prognosis. We decided to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of low versus high sodium intake in adults with CKD. Results:Our search strategy yielded seven studies from six countries with 465 participants. The overall effect on restricted sodium intake favored reduction in systolic blood pressure with an overall mean difference of -6.14(95% CI: -9.52, -2.76) and reduction in diastolic blood pressure with a mean difference of -3.08 (95% CI: -4.62, -1.55). There was lowering of estimated glomerular filtration rate (eGFR), however the same was not statistically significant.Conclusion:The study found that restricted salt intake could significantly reduce systolic and diastolic BP. Further, multi-center RCTs for longer durations across different stages of CKD could effectively assess the effects of restricted sodium intake on vital parameters. Such study designs could also help clinicians identify the optimal intake of dietary sodium to achieve better renal and cardio vascular outcomes.

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Hypertension and nutrition in the young: early intervention?

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y86-146 ◽

1986 ◽

Vol 64 (6) ◽

pp. 849-851 ◽

Cited By ~ 1

Author(s):

W. H. Weidman

Keyword(s):

Blood Pressure ◽

Body Size ◽

Early Intervention ◽

Family History ◽

Children And Adolescents ◽

Salt Intake ◽

Sodium Intake ◽

Primary Hypertension ◽

Dietary Sodium ◽

History Of

The few studies, carried out on infants, children, and adolescents, relating blood pressure to sodium intake have shown a weak positive correlation in some but not all individuals. The effect of body size on blood pressure confounds the interpretation of the effect of dietary sodium on blood pressure. There appear to be sodium-sensitive and sodium-unsensitive infants, children, and adolescents and is probably genetically transmitted. Most infants, children, and adolescents in industrialized populations have a salt intake far greater than required, and reduction in dietary sodium is safe and may be beneficial to those individuals with a family history of primary hypertension.

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

Hypertension ◽

10.1161/hypertensionaha.120.16186 ◽

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.

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Immunoreactive Substance P in Human Plasma: Response to Changes in Posture and Sodium Balance

Clinical Science ◽

10.1042/cs0590075 ◽

1980 ◽

Vol 59 (1) ◽

pp. 75-77 ◽

Cited By ~ 6

Author(s):

H. J. Kramer ◽

R. Düsing ◽

H. Stelkens ◽

R. Heinrich ◽

J. Kipnowski ◽

...

Keyword(s):

Substance P ◽

Salt Intake ◽

Sodium Intake ◽

Plasma Concentrations ◽

Mean Value ◽

Dietary Sodium ◽

Sodium Balance ◽

Dietary Salt ◽

Dietary Salt Intake ◽

High Sodium

1. In healthy volunteers plasma concentrations of immunoreactive substance P were measured in response to changes in posture and dietary salt intake. 2. In 14 subjects plasma immunoreactive substance P was 168 ± 31 pmol/l when subjects were supine and 401 ± 51 pmol/l (P < 0.001) when they were ambulant. 3. Measurement of supine plasma immunoreactive substance P at 6 h intervals gave a mean value of 240 ± 39 pmol/l at 14.00 hours and a lowest value of 76 ± 9 pmol/l at 02.00 hours. 4. In eight healthy subjects plasma immunoreactive substance P rose only slightly from 169 ± 41 pmol/l, on a sodium intake ad lib., to 244 ± 45 pmol/l by day 4 of dietary sodium restriction (35 mmol/day) and significantly fell to 51 ± 20 pmol/l (P < 0.001) by day 4 of high sodium intake (350 mmol/day). 5. Although exogenous substance P was shown to be natriuretic in dog and rat, the present results do not favour a role of endogenous substance P as a circulating natriuretic factor in man.

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Role of renal nerves in maintaining sodium balance in unrestrained conscious rats

AJP Renal Physiology ◽

10.1152/ajprenal.1985.249.6.f819 ◽

1985 ◽

Vol 249 (6) ◽

pp. F819-F826 ◽

Cited By ~ 3

Author(s):

E. Fernandez-Repollet ◽

C. R. Silva-Netto ◽

R. E. Colindres ◽

C. W. Gottschalk

Keyword(s):

Blood Pressure ◽

Renal Denervation ◽

Sodium Intake ◽

Plasma Renin ◽

Dietary Sodium ◽

Sodium Balance ◽

Renal Nerves ◽

Sodium Restriction ◽

Low Sodium ◽

Dietary Sodium Restriction

This study was designed to investigate the effects of bilateral renal denervation on sodium and water balance, the renin-angiotensin system, and systemic blood pressure in unrestrained conscious rats maintained on a normal- or low-sodium diet. Renal denervation was proven by chemical and functional tests. Both bilaterally denervated rats (n = 18) and sham-denervated rats (n = 15) maintained positive sodium balance while on a normal sodium intake. Both groups were in negative sodium balance for 1 day after dietary sodium restriction was instituted but were in positive sodium balance for the following 9 days. Systolic blood pressure was higher in sham-denervated (115 +/- 3 mmHg) than in denervated rats (102 +/- 3 mmHg) while on a normal diet (P less than 0.05) and remained so during sodium restriction. Plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were significantly diminished in the denervated rats during normal sodium intake (P less than 0.05). After dietary sodium restriction, PRC increased in both groups but remained significantly lower in the denervated rats (P less than 0.05). Following dietary sodium restriction, PAC also increased significantly to levels that were similar in both groups of rats. These results demonstrate that awake unrestrained growing rats can maintain positive sodium balance on a low sodium intake even in the absence of the renal nerves. However, efferent renal nerve activity influenced plasma renin activity in these animals.

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The role of caloric intake in the association of high salt intake with high blood pressure

Scientific Reports ◽

10.1038/s41598-021-95216-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Naftali Stern ◽

Assaf Buch ◽

Rebecca Goldsmith ◽

Lesley Nitsan ◽

Miri Margaliot ◽

...

Keyword(s):

Blood Pressure ◽

Sodium Excretion ◽

Salt Intake ◽

Sodium Intake ◽

Substantial Reduction ◽

Caloric Intake ◽

Community Dwelling ◽

Dietary Sodium ◽

Cross Sectional Survey ◽

High Salt Intake

AbstractSince current recommendations call for a substantial reduction in overall sodium consumption, we tested whether or not these recommendations are implemented in common large subpopulations such as those with abnormal weight or hypertension in the current high sodium, high-calorie nutritional environment. In a national representative cross-sectional survey of the community-dwelling subjects aged 25–65 years conducted in Israel between 2015 and 2017, 582 randomly selected subjects completed health and dietary questionnaires, underwent blood pressure and anthropometric measurements and collected 24-h urine specimens, to assess dietary sodium intake. Overall mean 24-h sodium excretion was 3834 mg, more than double the recommended upper intake for adults < 1500 mg/day. Sodium excretion was directly related to caloric intake and blood pressure and linked to the presence of hypertension and overweight/obesity. The highest sodium excretion was seen in overweight/obese hypertensive subjects. This recent national survey shows a high consumption of sodium in the Israeli population and a dose–response association between caloric intake and urinary sodium excretion, independent of BMI and hypertension. Nevertheless, overweight/obese subjects with hypertension consume (excrete) more sodium than other BMI/ blood pressure-related phenotypes and may thus comprise a target subpopulation for future efforts to reduce sodium intake.

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Estimation of salt intake, potassium intake and sodium-to-potassium ratio by 24-hour urinary excretion: an urban rural study in Sri Lanka

10.1101/2020.04.17.20068833 ◽

2020 ◽

Author(s):

R Jayatissa ◽

Y Yamori ◽

AH De Silva ◽

M Mori ◽

PC De Silva ◽

...

Keyword(s):

Blood Pressure ◽

Waist Circumference ◽

Sri Lanka ◽

Salt Intake ◽

Sodium Intake ◽

Dietary Sodium ◽

Sodium Potassium ◽

Salt Reduction ◽

Potassium Intake ◽

Salt Consumption

AbstractBackgroundSodium intakes of different populations around the world became of interest after a positive correlation was drawn between dietary sodium intake and prevalence of hypertension. Sri Lanka has adopted a salt reduction strategy to combat high blood pressure in the population with escalation of non-communicable diseases.ObjectiveTo measure intake of salt, potassium and sodium/potassium ratio of adults in urban and rural settings.DesignA community based study of 328 adults between 30-59 years, including equal numbers from urban and rural sectors. Weight, height and waist circumference were measured. Blood pressure was measured by a standardized automated measurement system and the mean of two readings was used for analysis. 24-hour urine was collected and measured for creatinine, sodium, potassium levels.ResultsMean daily salt consumption was 8.3g (95%CI:7.9,8.8), which is 1.6 times higher than WHO recommendation. Mean daily potassium intake was 1,265g (95%CI:1191.0,1339.3), which is 2.8 times lower and sodium/potassium ratio was 4.3 (95%CI:4.2,4.5), which is 7 times higher than WHO recommendation. Daily salt consumption was significantly higher in males (9.0g;95%CI:8.3,9.8) than females (7.7g;95%CI:7.2,8.2); rural (8.9g;95%CI:8.2-9.6,) than urban (7.7g;95%CI:7.2,8.3) with increasing body mass index (8.2g;95%CI:6.1,10.2 to 10.0g;95%CI:8.5,11.6). Systolic blood pressure was significantly positively correlated with high BMI and waist circumference.ConclusionsHigh salt consumption, low potassium intake and high sodium/potassium ratio was found in this population. This information can be used to set targets to reduce salt intake in the population. Need to create awareness to enhance the consumption of potassium rich food while reducing salt intake to minimize future NCD burden.

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Sensory Afferent Renal Nerve Activated Gαi2 Subunit Proteins Mediate the Natriuretic, Sympathoinhibitory and Normotensive Responses to Peripheral Sodium Challenges

Frontiers in Physiology ◽

10.3389/fphys.2021.771167 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jesse D. Moreira ◽

Kayla M. Nist ◽

Casey Y. Carmichael ◽

Jill T. Kuwabara ◽

Richard D. Wainford

Keyword(s):

Blood Pressure ◽

Volume Expansion ◽

Salt Intake ◽

Sodium Intake ◽

Salt Sensitivity ◽

Dietary Sodium ◽

Whole Body ◽

Renal Nerves ◽

Acute Administration ◽

Resistant Phenotype

We have previously reported that brain Gαi2 subunit proteins are required to maintain sodium homeostasis and are endogenously upregulated in the hypothalamic paraventricular nucleus (PVN) in response to increased dietary salt intake to maintain a salt resistant phenotype in rats. However, the origin of the signal that drives the endogenous activation and up-regulation of PVN Gαi2 subunit protein signal transduction pathways is unknown. By central oligodeoxynucleotide (ODN) administration we show that the pressor responses to central acute administration and central infusion of sodium chloride occur independently of brain Gαi2 protein pathways. In response to an acute volume expansion, we demonstrate, via the use of selective afferent renal denervation (ADNX) and anteroventral third ventricle (AV3V) lesions, that the sensory afferent renal nerves, but not the sodium sensitive AV3V region, are mechanistically involved in Gαi2 protein mediated natriuresis to an acute volume expansion [peak natriuresis (μeq/min) sham AV3V: 43 ± 4 vs. AV3V 45 ± 4 vs. AV3V + Gαi2 ODN 25 ± 4, p < 0.05; sham ADNX: 43 ± 4 vs. ADNX 23 ± 6, AV3V + Gαi2 ODN 25 ± 3, p < 0.05]. Furthermore, in response to chronically elevated dietary sodium intake, endogenous up-regulation of PVN specific Gαi2 proteins does not involve the AV3V region and is mediated by the sensory afferent renal nerves to counter the development of the salt sensitivity of blood pressure (MAP [mmHg] 4% NaCl; Sham ADNX 124 ± 4 vs. ADNX 145 ± 4, p < 0.05; Sham AV3V 125 ± 4 vs. AV3V 121 ± 5). Additionally, the development of the salt sensitivity of blood pressure following central ODN-mediated Gαi2 protein down-regulation occurs independently of the actions of the brain angiotensin II type 1 receptor. Collectively, our data suggest that in response to alterations in whole body sodium the peripheral sensory afferent renal nerves, but not the central AV3V sodium sensitive region, evoke the up-regulation and activation of PVN Gαi2 protein gated pathways to maintain a salt resistant phenotype. As such, both the sensory afferent renal nerves and PVN Gαi2 protein gated pathways, represent potential targets for the treatment of the salt sensitivity of blood pressure.

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