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

Background: High-salt intake often predisposes patients with left ventricular hypertrophy (LVH) to congestive heart failure. We hypothesized that high-salt intake superimposed on LVH activates brain epithelial Na channels (ENaC) and leads to sympathetic hyperactivation and LV dysfunction. Methods and Results: We used ICR mice and applied aortic banding (AB) to create LVH. Sham-operated mice served as control. Four weeks after AB, 24-h urinary norepinephrine excretion (U-NE) tended to increase rather than that in control (481±46 vs 354±42, n=10, p=0.09). AB hypertrophied LV wall thickness (WT) (2.2±0.6 vs 1.8±0.6 mm, n=8, p<0.05) without changing fractional shortening (%FS). We then fed the AB mice a high salt (8%) (AB-H) or regular salt (AB-R) diet for additional 4 weeks. AB-H depressed LV function (%FS: 27±2 vs 37±1%, n=8, p<0.05) and hypertrophied LVWT more than those in AB-R (WT: 2.8±0.5 vs 2.5±0.3 mm, n=8, p<0.05). U-NE was higher in AB-H than in AB-R (758±86 vs 459±35 ng/day, n=10, p<0.05). To examine the role of brain ENaC, we intracerebroventriculary (ICV) infused ENaC blocker (benzamil, 0.11μg/hr by osmotic pump) in AB-H for 4weeks. ENaC blocker decreased U-NE (567±35 vs 758±86 ng/day, n=10, p<0.05) and improved depressed LV function (%FS: 39±1 vs 28±3 %, n=10, p<0.05). To confirm the role of central Na in sympathetic hyperactivation and LV dysfunction, we administered, in AB with regular salt diet, high-Na (0.2 M) cerebrospinal fluid ICV (Na-ICV) (0.25μl/hr) for 2 weeks. Na-ICV significantly increased U-NE and deteriorates LV function (U-NE:987±103 ng/day, %FS: 31±1 %n=6) Conclusions: These results suggested that high-salt intake in the presence of LVH activates brain ENaC and leads to sympathetic hyperactivation and LV dysfunction.

Download Full-text

Blood pressure independent association of microalbuminuria and left ventricular hypertrophy in hypertensive men

Journal of Internal Medicine ◽

10.1046/j.1365-2796.2003.01155.x ◽

2003 ◽

Vol 254 (1) ◽

pp. 76-84 ◽

Cited By ~ 28

Author(s):

G. Dell'omo ◽

D. Giorgi ◽

V. Di Bello ◽

M. Mariani ◽

R. Pedrinelli

Keyword(s):

Blood Pressure ◽

Left Ventricular Hypertrophy ◽

Ventricular Hypertrophy ◽

Left Ventricular ◽

Pressure Independent ◽

Independent Association

Download Full-text

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.

Download Full-text

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.

Download Full-text

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

Download Full-text

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.

Download Full-text