Soybean proteins counteract heart remodeling in wistar rats fed a high sodium chloride diet

BACKGROUND. Increased salt intake is associated with a number of cardiovascular events, including increased blood pressure (BP) and the development of left ventricular hypertrophy (LVH). However, there is much evidence that a high content of sodium chloride in the diet does not always lead to an increase in BP, but almost inevitably causes cardiac remodeling, in particular, LVH. Many aspects of myocardial remodeling induced by high sodium content in the food have not been studied enough. THE AIM of the study was to trace the echocardiographic changes in Wistar rats fed the high salt ration and the high salt ration supplemented with soy proteins.MATERIAL AND METHODS. Echocardiography and BP measurements were performed on male Wistar rats, divided into three groups. The first (control; n = 8) included rats that received standard laboratory feed (20.16 % animal protein and 0.34 % NaCl); the second (n = 10) – animals that received standard feed and 8 % NaCl (high salt ration). The third group (n = 10) consisted of rats who consumed a low-protein diet containing 10 % soy protein isolate (SUPRO 760) and 8 % NaCl. The follow-up period was 2 and 4 months.THE RESULTS of the study showed that: (1) the intake of a large amount of salt with a diet does not necessarily lead to the formation of arterial hypertension; (2) despite the absence of a distinct increase in BP, under these conditions signs of cardiac remodeling, in particular, LVH, appear rather quickly; (3) supplementing a high-salt diet with soy isolates counteracts the development of LVH.CONCLUSION. High salt intake with food can cause heart remodeling, regardless of blood pressure, while soy proteins can counteract this process.

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MO079SOY PROTEINS PREVENT HEART REMODELING IN WISTAR RATS ON HIGH SODIUM CHLORIDE DIET

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab078.0015 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Olga Beresneva ◽

Marina Parastaeva ◽

Galina Ivanova ◽

Aleksander Kulikov ◽

Anatoly Kucher ◽

...

Keyword(s):

Blood Pressure ◽

Sodium Chloride ◽

Mitral Valve ◽

Left Ventricle ◽

Wistar Rats ◽

Interventricular Septum ◽

Soy Proteins ◽

High Sodium ◽

Group 3 ◽

Group 2

Abstract Background and Aims Increased salt intake has been linked to a number of poor effects, such as myocardial remodeling [1], independently of blood pressure level. Yet, many aspects of this remodeling are not well understood. The aim of the study was to find echocardiographic myocardial changes in Wistar rats on high sodium chloride (NaCl) diet, as well as to prove protective effects of diet, containing soy proteins. Method 28 male Wistar rats (age of 2.5-3.0 months) were enrolled in the observational prospective study (4 month) and subdivided into several groups. 1) Standard diet-Control group (C, n = 8, 20.16% protein of animal origin and 0.34% NaCl); 2) High salt diet (n = 10, 8% NaCl); 3) Low-protein diet (n=10, 10% soy protein (SUPRO 760) and 8% NaCl). Tail systolic blood pressure (BP) measurement, as well as echocardiographic examination were performed in anesthetized rats. Statistical analysis was performed with STATISTICA 10 software package. Fisher's LSD test was used. The significance level was <0.05. All data are presented as mean ± SEM. Results Keeping rats on a diet with 8% NaCl did not lead to significant changes in blood pressure (group 2 - 138.0 + 5.0, group 3 - 134.0 + 5.0 mm Hg), compared to C (135.0 + 5.0 mm Hg). On the contrary, left ventricle back wall width in rats of group 2 was significantly higher (1.83 ± 0.09 mm, p <0.02), than in C (1.49 ± 0.10 mm) or animals from group 3 (1, 47 ± 0.09mm). The values of end systolic left ventricle size, interventricular septum width, mitral valve systolic movement and tricuspid valve systolic movement in group 3 were significantly lower (1.67 ± 0.08 mm, 2.18 ± 0.13 mm, 2.70 ± 0.23 mm), than in group 2 (3.26 ± 0.33mm, p <0.037; 2.00 ± 0.12mm, p <0.043; 2.67mm ± 0.15, p <0.0124; 3.56 ± 0.34mm , p <0.0148, respectively). At the same time, left ventricular chamber size and thickness of interventricular septum did not differ significantly. In C animals, mitral valve movement (1.96 ± 0.09 mm; p <0.0008) and tricuspid valve movement (2.35 ± 0.07 mm; p<0.0012) were significantly lower than in rats of group 2 but not differed much from the values found in group 3. Conclusion High sodium containing diet does not necessarily lead to the development of arterial hypertension in Wistar rats, but may cause heart remodeling, while soy proteins counteracts the development of left ventricle hypertrophy, even in case of high sodium consumption.

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P0147THE EFFECT OF HIGH SODIUM CHLORIDE CONTENT IN THE DIET ON THE CARDIOVASCULAR SYSTEM OF MACACUS FASCICULARIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0147 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Sergey Orlov ◽

Olga Beresneva ◽

Aleksander Kulikov ◽

Marina Parastaeva ◽

Anatoly Kucher ◽

...

Keyword(s):

Blood Pressure ◽

Sodium Chloride ◽

Heart Function ◽

Salt Content ◽

Chloride Content ◽

High Salt ◽

Soy Proteins ◽

High Sodium ◽

The Third

Abstract Background and Aims It is traditionally believed that high consumption of sodium chloride leads to the development of arterial hypertension, which, in turn, will cause heart remodeling. However, more and more evidence is accumulating that a high sodium chloride content in the diet can cause heart damage without increasing blood pressure (BP). This is confirmed in experiments on rats. In addition, in animals of this species, supplementing a high-salt diet with soy proteins can prevent cardiovascular damage. Whether such mechanisms operate in primates remains unclear. Method The study was performed on male Macacus fascicularis. Monkeys were included in the experiment at the age of 4.6 -7.0 years and had a body weight of 5,5-7,5kg. Animals were divided into 3 groups. The first (control) included 5 animals, received standard ration; the second – 5 animals, received diet with high sodium chloride content (8 g NaCl/1 kg of the feed); the third – 6 animals, who were on a diet with high salt contents supplemented by soya isolated proteins (200 g/kg of the feed). In anesthetized animals measured blood pressure and performed an echocardiographic investigation. Follow up period lasted four month. Results Initially, in all groups of animals, blood pressure levels (Mean(SEM)) and echocardiographic parameters did not significantly differ. During the observation period, the studied parameters did not change much. For example, in the first group, an ejection fraction (EF) increased from 61.7(1.67) to 71.6(4.74), %; P=0.045. In the same group, a tendency toward a decrease in the left ventricle end-systolic dimension (1.50(0.056)vs 1.29(0.118), mm; P=0.079) was noted. Whereas the level of systolic and diastolic blood pressures in this group (for example, systolic BP: 115.4(3.95)vs 126.0(5.39), mm Hg; P=0.134) as well as in other groups of monkeys did not change significantly. Nevertheless, after four months of observation, the level of systolic blood pressure in the second group (126.0(5.39) mm Hg) of animals was significantly higher than in the first (103.0(5.54), P=0.0118) and nonsignificantly - in the third (104.0(8.39), mm Hg; P=0.065). EF in the end of follow up period in second group (71.6(4.74%) was significantly higher than in control (58.1(2.72),%; P=0.039) but not in the third group (60.9(5.03),%; P=0.162). Tricuspid annular plane systolic excursion in second group (1.02(0.08), mm) had an insignificant tendency to increase in comparison to the first (0.782(0.096), mm; P=0.094) or third (0.818(0.049), mm; P=0.052) groups. Conclusion Our data do not exclude the possibility that a high salt content in the food of lower primates can contribute to an increase in blood pressure and a change in heart function. However, to resolve the issues of the relationship between changes in heart function and the level of blood pressure and the presence of the cardioprotective effect of soy proteins under these conditions, longer observations are needed.

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The Relationship Between Urine Uromodulin and Blood Pressure Changes: The DASH-Sodium Trial

American Journal of Hypertension ◽

10.1093/ajh/hpaa140 ◽

2020 ◽

Author(s):

Christine Y Bakhoum ◽

Cheryl A M Anderson ◽

Stephen P Juraschek ◽

Casey M Rebholz ◽

Lawrence J Appel ◽

...

Keyword(s):

Blood Pressure ◽

Salt Intake ◽

Control Diet ◽

Random Order ◽

High Salt ◽

Thick Ascending Limb ◽

Feeding Period ◽

High Sodium ◽

Sodium Diet ◽

High Salt Intake

Abstract BACKGROUND Uromodulin modulates the sodium-potassium-two-chloride transporter in the thick ascending limb of the loop of Henle, and its overexpression in murine models leads to salt-induced hypertension. We hypothesized that individuals with higher baseline levels of urine uromodulin would have a greater increase in systolic blood pressure (SBP) for the same increase in sodium compared with those with lower uromodulin levels. METHODS We used data from 157 subjects randomized to the control diet of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial who were assigned to 30 days of low (1,500 mg/d), medium (2,400 mg/d), and high salt (3,300 mg/d) diets in random order. Blood pressure was measured prerandomization and then weekly during each feeding period. We evaluated the association of prerandomization urine uromodulin with change in SBP between diets, as measured at the end of each feeding period, using multivariable linear regression. RESULTS Baseline urine uromodulin stratified by tertiles was ≤17.64, 17.65–31.97, and ≥31.98 µg/ml. Across the tertiles, there were no significant differences in SBP at baseline, nor was there a differential effect of sodium diet on SBP across tertiles (low to high, P = 0.81). After adjusting for age, sex, body mass index, and race, uromodulin levels were not significantly associated with SBP change from low to high sodium diet (P = 0.42). CONCLUSIONS In a randomized trial of different levels of salt intake, higher urine uromodulin levels were not associated with a greater increase in blood pressure in response to high salt intake.

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Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases

Physiological Reviews ◽

10.1152/physrev.00056.2003 ◽

2005 ◽

Vol 85 (2) ◽

pp. 679-715 ◽

Cited By ~ 426

Author(s):

Pierre Meneton ◽

Xavier Jeunemaitre ◽

Hugh E. de Wardener ◽

Graham A. Macgregor

Keyword(s):

Blood Pressure ◽

Cardiovascular Diseases ◽

Salt Intake ◽

Causal Link ◽

Left Ventricular ◽

High Salt ◽

Human Populations ◽

Dietary Salt ◽

Dietary Salt Intake ◽

High Salt Intake

Epidemiological, migration, intervention, and genetic studies in humans and animals provide very strong evidence of a causal link between high salt intake and high blood pressure. The mechanisms by which dietary salt increases arterial pressure are not fully understood, but they seem related to the inability of the kidneys to excrete large amounts of salt. From an evolutionary viewpoint, the human species is adapted to ingest and excrete <1 g of salt per day, at least 10 times less than the average values currently observed in industrialized and urbanized countries. Independent of the rise in blood pressure, dietary salt also increases cardiac left ventricular mass, arterial thickness and stiffness, the incidence of strokes, and the severity of cardiac failure. Thus chronic exposure to a high-salt diet appears to be a major factor involved in the frequent occurrence of hypertension and cardiovascular diseases in human populations.

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Abstract 14650: A Monoclonal Antibody to a Sodium Pump Inhibitor Marinobufagenin Reversed Aortic Remodeling and Stiffness in Normotensive Rats on a High Salt Intake

Circulation ◽

10.1161/circ.130.suppl_2.14650 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Yulia Grigorova ◽

Wen Wei ◽

Valentina Zernetkina ◽

Ondrej Juhasz ◽

Edward Lakatta ◽

...

Keyword(s):

Blood Pressure ◽

Atpase Activity ◽

Salt Intake ◽

Left Ventricular ◽

High Salt ◽

Collagen Deposition ◽

Antibody Treatment ◽

Salt Diet ◽

Vasorelaxant Effect ◽

High Salt Intake

Background: Marinobufagenin (MBG), an endogenous cardiotonic steroid, is a Na/K-ATPase inhibitor and a vasoconstrictor. Previously it was demonstrated, that administration of 3E9 anti-MBG-antibody (mAb) reduced blood pressure (BP) and reversed left ventricular fibrosis in animal models of salt-sensitive hypertension and nephropathy. In the present study we investigated whether mAb alleviates BP and vascular remodeling in normotensive rats on a high salt intake. Methods: Wistar rats (5 months old) received normal salt diet (CTRL; n=8) or high salt intake (2% NaCl in drinking water) for 4 weeks. Rats on a high salt were administered vehicle (SALT; n=8) or mAb (50 ug/kg) (SALT-AB; n=8) 3 times during the last week of a high salt diet. BP was measured at baseline, after 3 and 4 weeks of experiment. Na/K-ATPase activity was measured in erythrocytes. Aortas were weighed, and were used to study sensitivity to the vasorelaxant effect of sodium nitroprusside (SNP), and for the histochemistry analysis of collagen deposition. Renal 24-hr MBG excretion was measured at week 4. Results: In SALT vs. CTRL, in the absence of BP changes, elevated levels of MBG (14.1±1.1 vs. 9.0±1.6 pmol/24hr, p<0.05) were associated with inhibition of erythrocyte Na/K-ATPase (12.6±0.3 vs. 14.2±0.35 μmol Pi/ml/hr, p<0.05), increased aortic weights (217±15 vs. 158±9 mg/kg BW, p<0.01), increased levels of collagen in aorta (2.5-fold; p<0.05), and compromised SNP vasorelaxant effect in aortic explants (EC50=167±19.3 nM vs. 99±2.0 nM; P<0.01). Antibody treatment in SALT-AB vs. SALT increased Na/K-ATPase activity (13.93±0.54 μmol Pi/ml/hr, p<0.05), reduced the aortic weight (180±12 mg/kg; P<0.05) and collagen deposition 3-fold (P<0.05), and restored the vasorelaxation of aortic rings by SNP to the levels in CTRL (70±1.5 nM, p<0.01). Conclusion: These findings for the first time demonstrated that in normotensive rats on a high salt intake heightened MBG levels induced vascular fibrosis and impairment of vasorelaxation in the absence of blood pressure changes. Immunoneutralization of MBG reversed these changes. Thus, high dietary NaCl intake in normotensive animals can stimulate vascular fibrosis via pressure-independent/ MBG-dependent mechanisms, and this remodeling is reversible.

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High salt intake: a cause of blood pressure-independent left ventricular hypertrophy?

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfm321 ◽

2007 ◽

Vol 22 (9) ◽

pp. 2426-2429 ◽

Cited By ~ 21

Author(s):

M. Burnier ◽

O. Phan ◽

Q. Wang

Keyword(s):

Blood Pressure ◽

Left Ventricular Hypertrophy ◽

Ventricular Hypertrophy ◽

Salt Intake ◽

Left Ventricular ◽

High Salt ◽

High Salt Intake ◽

Pressure Independent

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Sympathetic Regulation of the NCC (Sodium Chloride Cotransporter) in Dahl Salt–Sensitive Hypertension

Hypertension ◽

10.1161/hypertensionaha.120.15928 ◽

2020 ◽

Vol 76 (5) ◽

pp. 1461-1469

Author(s):

Franco Puleo ◽

Kiyoung Kim ◽

Alissa A. Frame ◽

Kathryn R. Walsh ◽

Mohammed Z. Ferdaus ◽

...

Keyword(s):

Blood Pressure ◽

Sodium Chloride ◽

Salt Intake ◽

High Salt ◽

Sodium Reabsorption ◽

Sprague Dawley ◽

Sodium Chloride Cotransporter ◽

High Salt Intake ◽

Sympathetic Regulation ◽

Salt Sensitive Hypertension

Increased sympathoexcitation and renal sodium retention during high salt intake are hallmarks of the salt sensitivity of blood pressure. The mechanism(s) by which excessive sympathetic nervous system release of norepinephrine influences renal sodium reabsorption is unclear. However, studies demonstrate that norepinephrine can stimulate the activity of the NCC (sodium chloride cotransporter) and promote the development of SSH (salt-sensitive hypertension). The adrenergic signaling pathways governing NCC activity remain a significant source of controversy with opposing studies suggesting a central role of upstream α 1 - and β-adrenoceptors in the canonical regulatory pathway involving WNKs (with-no-lysine kinases), SPAK (STE20/SPS1-related proline alanine-rich kinase), and OxSR1 (oxidative stress response 1). In our previous study, α 1 -adrenoceptor antagonism in norepinephrine-infused male Sprague-Dawley rats prevented the development of norepinephrine-evoked SSH in part by suppressing NCC activity and expression. In these studies, we used selective adrenoceptor antagonism in male Dahl salt–sensitive rats to test the hypothesis that norepinephrine-mediated activation of the NCC in Dahl SSH occurs via an α 1 -adrenoceptor dependent pathway. A high-salt diet evoked significant increases in NCC activity, expression, and phosphorylation in Dahl salt–sensitive rats that developed SSH. Increases were associated with a dysfunctional WNK1/4 dynamic and a failure to suppress SPAK/OxSR1 activity. α 1 -adrenoceptor antagonism initiated before high-salt intake or following the establishment of SSH attenuated blood pressure in part by suppressing NCC activity, expression, and phosphorylation. Collectively, our findings support the existence of a norepinephrine-activated α 1 -adrenoceptor gated pathway that relies on WNK/SPAK/OxSR1 signaling to regulate NCC activity in SSH.

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High salt intake induces left ventricular interstitial fibrosis by a blood pressure and angiotensin II type 1 receptor‐independent mechanism

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.626.9 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Daniele Nunes Ferreira ◽

Isis A. Katayama ◽

Ivone B. Oliveira ◽

Kaleizu T. Rosa ◽

Michella S. Coelho ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Salt Intake ◽

Interstitial Fibrosis ◽

Left Ventricular ◽

High Salt ◽

High Salt Intake ◽

Independent Mechanism

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Developing essential hypertension: a syndrome involving ANF deficiency?

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-235 ◽

1991 ◽

Vol 69 (10) ◽

pp. 1582-1591 ◽

Cited By ~ 13

Author(s):

P. Weidmann ◽

P. Ferrari ◽

Y. Allemann ◽

C. Ferrier ◽

S. G. Shaw

Keyword(s):

Blood Pressure ◽

Essential Hypertension ◽

Cyclic Gmp ◽

Vascular Reactivity ◽

Salt Intake ◽

Deficiency Syndrome ◽

Left Ventricular ◽

High Salt ◽

Cardiac Complications ◽

High Salt Intake

The pathogenesis of essential hypertension may possibly involve a deficiency in, or a decreased response to, endogenous vasodilator and natriuretic factor(s). Searching for hereditary or familial defects, it is plausible to evaluate blood pressure (BP) regulating factors in (yet) normotensive offspring of hypertensive parents (OHyp), some of whom are in fact in a stage of prehypertension. Studies by our group demonstrated that compared with healthy offspring of normotensive parents, OHyp have plasma atrial natriuretic (ANF) factor levels that are unaltered on a low salt intake but often fail to increase normally in response to a high salt intake. Plasma levels of cyclic GMP, the presumed second messenger of ANF, also may tend to be decreased in certain OHyp. On the other hand, renal excretory responses of cyclic GMP and electrolytes to ANF infused in "physiological" dose were unchanged in some OHyp tested so far. In borderline to moderate, uncomplicated essential hypertension, plasma ANF levels are often "normal." This may be inappropriately low relative to the existing BP, although the relationship of circulating ANF to atrial pressures in essential hypertension remains to be clarified. A conversion to higher plasma ANF values may occur with cardiac complications such as left ventricular hypertrophy, enlargement, dysfunction, or overt heart failure. Acute or short-term elevation of circulating ANF within the physiological and pathophysiological range by ANF infusion produces an exaggerated natriuresis and lowers BP in essential hypertensive patients. We postulate a syndrome of ANF deficiency, characterized by an impaired response of circulating ANF to high salt intake and by low cyclic GMP levels in certain yet normotensive offspring of essential hypertensive parents and by inappropriately "normal" plasma ANF in some patients with uncomplicated essential hypertension. At the stage of prehypertension, a disturbance in the ANF – cyclic GMP pathway may be expressed primarily at the circulatory rather than at the renal level. Hypertension-prone humans also tend to have an exaggerated vascular reactivity to norepinephrine. Whether the two disturbances may be interrelated is presently unknown. Both defects may potentially predispose to the development of essential hypertension. Relative ANF deficiency, an enhanced natriuretic response to ANF, and a sustained antihypertensive effect of infused ANF may represent a rational basis for treatment of essential hypertension with agents that activate the ANF system.Key words: offspring of hypertensive parents, essential hypertension, ANF, ANF deficiency syndrome, cyclic GMP, blood pressure regulation, vascular reactivity, renal function.

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