scispace - formally typeset
Search or ask a question
Journal ArticleDOI

23Na Magnetic Resonance Imaging-Determined Tissue Sodium in Healthy Subjects and Hypertensive Patients

01 Mar 2013-Hypertension (Lippincott Williams & WilkinsHagerstown, MD)-Vol. 61, Iss: 3, pp 635-640
TL;DR: 23Na magnetic resonance imaging could have utility in assessing the role of tissue Na+ storage for cardiovascular morbidity and mortality in longitudinal studies, and it is suggested that patients with refractory hypertension had increased tissueNa+ content, compared with normotensive controls.
Abstract: High dietary salt intake is associated with hypertension; the prevalence of salt-sensitive hypertension increases with age. We hypothesized that tissue Na(+) might accumulate in hypertensive patients and that aging might be accompanied by Na(+) deposition in tissue. We implemented (23)Na magnetic resonance imaging to measure Na(+) content of soft tissues in vivo earlier, but had not studied essential hypertension. We report on a cohort of 56 healthy control men and women, and 57 men and women with essential hypertension. The ages ranged from 22 to 90 years. (23)Na magnetic resonance imaging measurements were made at the level of the calf. We observed age-dependent increases in Na(+) content in muscle in men, whereas muscle Na(+) content did not change with age in women. We estimated water content with conventional MRI and found no age-related increases in muscle water in men, despite remarkable Na(+) accumulation, indicating water-free Na(+) storage in muscle. With increasing age, there was Na(+) deposition in the skin in both women and men; however, skin Na(+) content remained lower in women. Similarly, this sex difference was found in skin water content, which was lower in women than in men. In contrast to muscle, increasing Na(+) content was paralleled with increasing skin water content. When controlled for age, we found that patients with refractory hypertension had increased tissue Na(+) content, compared with normotensive controls. These observations suggest that (23)Na magnetic resonance imaging could have utility in assessing the role of tissue Na(+) storage for cardiovascular morbidity and mortality in longitudinal studies.
Citations
More filters
Journal ArticleDOI
TL;DR: The results suggest that the skin contains a hypertonic interstitial fluid compartment in which MPS cells exert homeostatic and blood pressure-regulatory control by local organization of interstitial electrolyte clearance via TONEBP and VEGFC/VEGFR3-mediated modification of cutaneous lymphatic capillary function.
Abstract: The skin interstitium sequesters excess Na+ and Cl- in salt-sensitive hypertension. Mononuclear phagocyte system (MPS) cells are recruited to the skin, sense the hypertonic electrolyte accumulation in skin, and activate the tonicity-responsive enhancer-binding protein (TONEBP, also known as NFAT5) to initiate expression and secretion of VEGFC, which enhances electrolyte clearance via cutaneous lymph vessels and increases eNOS expression in blood vessels. It is unclear whether this local MPS response to osmotic stress is important to systemic blood pressure control. Herein, we show that deletion of TonEBP in mouse MPS cells prevents the VEGFC response to a high-salt diet (HSD) and increases blood pressure. Additionally, an antibody that blocks the lymph-endothelial VEGFC receptor, VEGFR3, selectively inhibited MPS-driven increases in cutaneous lymphatic capillary density, led to skin Cl- accumulation, and induced salt-sensitive hypertension. Mice overexpressing soluble VEGFR3 in epidermal keratinocytes exhibited hypoplastic cutaneous lymph capillaries and increased Na+, Cl-, and water retention in skin and salt-sensitive hypertension. Further, we found that HSD elevated skin osmolality above plasma levels. These results suggest that the skin contains a hypertonic interstitial fluid compartment in which MPS cells exert homeostatic and blood pressure-regulatory control by local organization of interstitial electrolyte clearance via TONEBP and VEGFC/VEGFR3-mediated modification of cutaneous lymphatic capillary function.

345 citations


Cites background from "23Na Magnetic Resonance Imaging-Det..."

  • ...org Volume 123 Number 7 July 2013 2811 magnetic resonance imaging techniques to make Na+ storage visible in animals and patients (67, 68) and have shown that essential hypertension in humans is paralleled by tissue Na+ storage (69)....

    [...]

Journal ArticleDOI
TL;DR: Understanding of its pivotal mechanisms may lead to specific therapies to decrease the cardiovascular risk associated with this trait in humans, and identification of biochemical or genetic markers of salt-sensitivity for use in the clinic would improve risk stratification of hypertensive and prehypertensive subjects.
Abstract: Salt-sensitivity of blood pressure is an abnormal phenotype that confers increased cardiovascular morbidity. We discuss its underlying renal mechanisms, including the role of systems that regulate renal salt handling. We review knockout and congenic strains that have unraveled participation of several genes in rodents inbred to produce pure salt-sensitive and salt-resistant substrains. In humans, salt-sensitivity is a continuous variable, hence, defined with arbitrary cutoffs for blood pressure responses to salt-loading or deprivation. Nonetheless, clustering of phenotypic characteristics in salt-sensitive subjects suggests an inherited component for this trait. This is supported by relationships between salt-sensitivity and gene polymorphisms in renal transporters, vasoactive substances and oxidative systems. Identification of biochemical or genetic markers of salt-sensitivity for use in the clinic would improve risk stratification of hypertensive and prehypertensive subjects. Understanding of its pivotal mechanisms may lead to specific therapies to decrease the cardiovascular risk associated with this trait in humans.

314 citations

Journal ArticleDOI
TL;DR: An overview of some of the latest methodological developments in human ultra-high field MRI/MRS as well as associated clinical and scientific applications is presented, with emphasis on techniques that particularly benefit from the changing physical characteristics at high magnetic fields.

300 citations


Cites background from "23Na Magnetic Resonance Imaging-Det..."

  • ...myotonic dystrophy [358,359], Duchenne muscular dystrophy [360,361], hypertension [362], severe kidney disease [363], heart failure [364], and muscular channelopathies [365–367]....

    [...]

Journal ArticleDOI
TL;DR: The effects of sodium intake on vascular hemodynamics and their implication in the pathogenesis of hypertension are focused on and include changes in the structure and function of large elastic arteries, modification in sympathetic activity, and in the autonomic neuronal modulation of the cardiovascular system.
Abstract: 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.

266 citations


Cites background from "23Na Magnetic Resonance Imaging-Det..."

  • ...The emerging magnetic resonance imaging–based techniques that directly detect Na+ in tissues [81] have recently provided confirmation and further evidence about the compartmentalized sodium storage in humans, also in relation to cardiovascular morbidities [82]....

    [...]

Journal ArticleDOI
TL;DR: The simplest definition of salt sensitivity of blood pressure (SSBP) states that it is a physiological trait present in rodents and other mammals, including humans, by which the blood pressure of some members of the population exhibits changes parallel to changes in salt intake as discussed by the authors.
Abstract: The simplest definition of salt sensitivity of blood pressure (SSBP) states that it is a physiological trait present in rodents and other mammals, including humans, by which the blood pressure (BP) of some members of the population exhibits changes parallel to changes in salt intake. In animals, the trait has been inbred such that the salt-sensitive (SS) ones will sustain increases in BP with salt loading and decreases with salt depletion, whereas the salt resistant (SR) ones will not. In humans, the trait is normally distributed; therefore, the distinction between SS and SR members of the population has been made by choosing an arbitrary magnitude of the salt-induced change in BP to define the groups. Regardless of possible causation by abnormalities of sodium handling, the SS phenotype is not usually characterized by alterations in salt balance (eg, impaired natriuresis or expanded plasma volume) but rather by a hypertensive response to maintain it. In an unselected population, SSBP is a continuous, normally distributed quantitative trait.1 As with any other trait with these characteristics, there is the issue of whether population members with the largest and smallest quantities of the trait represent the randomness of its distribution or are qualitatively different from the population at large. An example of this controversy is the old analyses of the unimodality versus bimodality of BP incidence or prevalence in humans that tried to determine whether hypertension is a distinct entity or simply an extreme of the gaussian distribution of BP.2 The development of the spontaneously hypertensive rat by Japanese investigators3 showing that the trait could be selected by inbreeding made it clear that hypertension had a genetic component. The gaussian distribution of population BP is probably the result of a random mixture of prohypertensive and antihypertensive genes and genetic variants in a …

251 citations

References
More filters
Journal ArticleDOI
TL;DR: awareness, treatment, and control of hypertension have improved substantially since the 1976-1980 National Health and Nutrition Examination Survey but continue to be suboptimal, especially in Mexican Americans.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The purpose of this study was to estimate the current prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment, and control in the US adult population. The study used a cross-sectional survey of the civilian, noninstitutionalized population of the United States, including an in-home interview and a clinic examination, each of which included measurement of blood pressure. Data for 9901 participants 18 years of age and older from phase 1 of the third National Health and Nutrition Examination Survey, collected from 1988 through 1991, were used. Twenty-four percent of the US adult population representing 43 186 000 persons had hypertension. The age-adjusted prevalence in the non-Hispanic black, non-Hispanic white, and Mexican American populations was 32.4%, 23.3%, and 22.6%, respectively. Overall, two thirds of the population with hypertension were aware of their diagnosis (69%), and a majority were taking prescribed medication (53%). Only one third of Mexican Americans with hypertension were being treated (35%), and only 14% achieved control in contrast to 25% and 24% of the non-Hispanic black and non-Hispanic white populations with hypertension, respectively. Almost 13 million adults classified as being normotensive reported being told on one or more occasions that they had hypertension; 51% of this group reported current adherence to lifestyle changes to control their hypertension. Hypertension continues to be a common finding in the general population. Awareness, treatment, and control of hypertension have improved substantially since the 1976-1980 National Health and Nutrition Examination Survey but continue to be suboptimal, especially in Mexican Americans. Consideration should be given to revision of the criteria for classification of hypertension to reflect the widespread use of lifestyle modification for treatment of hypertension.

3,051 citations

Journal ArticleDOI
23 Feb 2001-Cell
TL;DR: Supported in part by a Specialized Center of Research in Hypertension and NIH K08 awards (to A. G. and D. S. G.) and a grant from the Howard Hughes Medical Institute.

1,628 citations


"23Na Magnetic Resonance Imaging-Det..." refers background in this paper

  • ...Mendelian forms of hypertension have underscored the role of salt intake in the development of hypertension.(2) Clinicians have advised patients in terms of their dietary intake and have relied on 24 hour urine collections to verify dietary compliance....

    [...]

Journal ArticleDOI
TL;DR: It is shown that a high-salt diet in rats leads to interstitial hypertonic Na+ accumulation in skin, resulting in increased density and hyperplasia of the lymphcapillary network and VEGFC is identified as an osmosensitive, hypertonicity-driven gene intimately involved in salt-induced hypertension.
Abstract: In salt-sensitive hypertension, the accumulation of Na(+) in tissue has been presumed to be accompanied by a commensurate retention of water to maintain the isotonicity of body fluids We show here that a high-salt diet (HSD) in rats leads to interstitial hypertonic Na(+) accumulation in skin, resulting in increased density and hyperplasia of the lymphcapillary network The mechanisms underlying these effects on lymphatics involve activation of tonicity-responsive enhancer binding protein (TonEBP) in mononuclear phagocyte system (MPS) cells infiltrating the interstitium of the skin TonEBP binds the promoter of the gene encoding vascular endothelial growth factor-C (VEGF-C, encoded by Vegfc) and causes VEGF-C secretion by macrophages MPS cell depletion or VEGF-C trapping by soluble VEGF receptor-3 blocks VEGF-C signaling, augments interstitial hypertonic volume retention, decreases endothelial nitric oxide synthase expression and elevates blood pressure in response to HSD Our data show that TonEBP-VEGF-C signaling in MPS cells is a major determinant of extracellular volume and blood pressure homeostasis and identify VEGFC as an osmosensitive, hypertonicity-driven gene intimately involved in salt-induced hypertension

838 citations


"23Na Magnetic Resonance Imaging-Det..." refers background in this paper

  • ...Our earlier ashing studies indicated that the bone storage is minimal, and that instead large quantities are stored in the skin.(5,6) The skin is abundant in branching glycosaminoglycans that possess a strong negative charge, largely because of their sulfate content....

    [...]

  • ...We showed recently that signaling mechanisms exist in skin that control skin electrolyte storage.(6) When these mechanisms are perturbed, salt-sensitive hypertension results....

    [...]

Journal ArticleDOI
TL;DR: Long-term follow-up of normotensive salt-sensitive subjects in whom assessment of salt sensitivity of blood pressure was performed as long as 27 years ago provides unique evidence of a relationship between salt sensitivity and mortality that is independent of elevated blood pressure.
Abstract: Although factors such as age, blood pressure, and its responsiveness to changes in sodium balance and extracellular fluid volume status (salt sensitivity) are associated with an increased risk of end-organ disease and cardiovascular events in hypertensive subjects, no such relationship with mortality has been demonstrated for salt sensitivity in normotensive subjects. We conducted long-term follow-up of 430 normal and 278 hypertensive subjects in whom assessment of salt sensitivity of blood pressure was performed as long as 27 years ago. We ascertained the status of 596 subjects (85% of the total population), 123 (21%) of whom had died. The following initial measurements were significantly (P 25 years when initially studied were found to have a cumulative mortality similar to that of hypertensive subjects, whereas salt-resistant normotensive subjects had increased survival ( P

509 citations


"23Na Magnetic Resonance Imaging-Det..." refers background in this paper

  • ...The issue is important, as salt-sensitivity portends an earlier death.(4) Na is bound to negatively charged proteoglycans that are very abundant in the skin, the body’s largest organ....

    [...]

Journal ArticleDOI
TL;DR: This article reviews the most commonly used techniques for fat suppression and fat–water imaging including 1) chemically selective fat suppression pulses “FAT‐SAT”; 2) spatial‐spectral pulses (water excitation); 3) short inversion time (TI) inversion recovery (STIR) imaging; 4) chemical shift based water–fat separation methods; and finally 5)Fat suppression and balanced steady‐state free precession (SSFP) sequences.
Abstract: A wide variety of fat suppression and water-fat separation methods are used to suppress fat signal and improve visualization of abnormalities. This article reviews the most commonly used techniques for fat suppression and fat-water imaging including 1) chemically selective fat suppression pulses "FAT-SAT"; 2) spatial-spectral pulses (water excitation); 3) short inversion time (TI) inversion recovery (STIR) imaging; 4) chemical shift based water-fat separation methods; and finally 5) fat suppression and balanced steady-state free precession (SSFP) sequences. The basic physical background of these techniques including their specific advantages and disadvantages is given and related to clinical applications. This enables the reader to understand the reasons why some fat suppression methods work better than others in specific clinical settings.

328 citations


"23Na Magnetic Resonance Imaging-Det..." refers methods in this paper

  • ...5×5 mm(3)), as described by other investigators.(8) Here, the 10 mmol/L NaCl tube served as a calibration standard for tissue water....

    [...]

Related Papers (5)