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  1. Article ; Online: Quantifying salt sensitivity.

    Oberleithner, Hans

    Biological chemistry

    2021  Volume 402, Issue 12, Page(s) 1597–1602

    Abstract: Inner surfaces of blood vessels and outer surfaces of erythrocytes are coated with a negatively charged protective film of proteoglycans, which serves as an effective buffer system for the positively charged sodium ions. If this protective coating is ... ...

    Abstract Inner surfaces of blood vessels and outer surfaces of erythrocytes are coated with a negatively charged protective film of proteoglycans, which serves as an effective buffer system for the positively charged sodium ions. If this protective coating is poorly developed or impaired, it loses its buffering capacity. As a consequence, the organism becomes increasingly sensitive to sodium, which in the long run leads to organ damage, especially if daily salt consumption is high. Recently, it has become possible to quantify salt sensitivity using a technically simple method - the salt blood test (SBT). Aim of this mini-review is to explain the physiological concept underlying the SBT and its potential practical relevance in the prevention of cardiovascular disease.
    MeSH term(s) Erythrocytes ; Humans ; Hypertension ; Sodium
    Chemical Substances Sodium (9NEZ333N27)
    Language English
    Publishing date 2021-09-10
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1334659-3
    ISSN 1437-4315 ; 1431-6730 ; 1432-0355
    ISSN (online) 1437-4315
    ISSN 1431-6730 ; 1432-0355
    DOI 10.1515/hsz-2021-0206
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  2. Article ; Online: Sodium selective erythrocyte glycocalyx and salt sensitivity in man.

    Oberleithner, Hans

    Pflugers Archiv : European journal of physiology

    2014  Volume 467, Issue 6, Page(s) 1319–1325

    Abstract: Negatively charged surfaces of erythrocytes (RBC) reflect properties of the endothelial glycocalyx. Plasma electrolytes counteract these charges and thus control the repulsive forces between RBC and endothelium. Although Na(+) is supposed to exert a ... ...

    Abstract Negatively charged surfaces of erythrocytes (RBC) reflect properties of the endothelial glycocalyx. Plasma electrolytes counteract these charges and thus control the repulsive forces between RBC and endothelium. Although Na(+) is supposed to exert a rather high affinity to the RBC surface, a direct comparison between Na(+) and K(+) in counteracting the RBC surface has been never made. Therefore, we measured Na(+)/K(+) selectivity of the RBC surface in 20 healthy volunteers applying the previously published salt blood test (SBT). It turned out that the Na(+)/K(+) selectivity ratio of the RBC glycocalyx is on average 6.1 ± 0.39 (ranging from 3 to 9 in different individuals). Considering standard plasma Na(+) and K(+) concentrations, binding probability of Na(+)/K(+) at the RBC surface is about 180:1. The SBT reveals that plasma K(+) counteracts only about 7% of the negative charges in the RBC glycocalyx. As an in vivo proof of principle, a volunteer's blood was continuously tested over 6 months while applying a glycocalyx protective polyphenol-rich natural compound (hawthorn extract). It turned out that RBC Na(+) sensitivity (the inverse of Na(+) buffer capacity) decreased significantly by about 25% while Na(+)/K(+) selectivity of the RBC glycocalyx declined only slightly by about 8 %. Taken together, (i) plasma Na(+) selectively buffers the negative charges of the RBC glycocalyx, (ii) the contribution of K(+) in counteracting these negative surface charges is small, and (iii) natural polyphenols applied in vivo increase RBC surface negativity. In conclusion, low plasma Na(+) is supposed to favor frictionless RBC-slipping through blood vessels.
    MeSH term(s) Cell Membrane/drug effects ; Cell Membrane/metabolism ; Cells, Cultured ; Crataegus/chemistry ; Erythrocytes/drug effects ; Erythrocytes/metabolism ; Glycocalyx/drug effects ; Glycocalyx/metabolism ; Humans ; Plant Extracts/pharmacology ; Polyphenols/pharmacology ; Potassium/blood ; Potassium/pharmacology ; Sodium/blood ; Sodium/pharmacology ; Static Electricity ; Young Adult
    Chemical Substances Plant Extracts ; Polyphenols ; Sodium (9NEZ333N27) ; Potassium (RWP5GA015D)
    Language English
    Publishing date 2014-07-17
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-014-1577-0
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  3. Article ; Online: Vascular endothelium: a vulnerable transit zone for merciless sodium.

    Oberleithner, Hans

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2014  Volume 29, Issue 2, Page(s) 240–246

    Abstract: In humans, when plasma sodium concentration rises slightly beyond 140 mM, vascular endothelium sharply stiffens and nitric oxide release declines. In search of a vascular sodium sensor, the endothelial glycocalyx was identified as being a negatively ... ...

    Abstract In humans, when plasma sodium concentration rises slightly beyond 140 mM, vascular endothelium sharply stiffens and nitric oxide release declines. In search of a vascular sodium sensor, the endothelial glycocalyx was identified as being a negatively charged biopolymer capable of selectively buffering sodium ions. Sodium excess damages the glycocalyx and renders vascular endothelium increasingly permeable for sodium. In the long term, sodium accumulates in the interstitium and gradually damages the organism. It was discovered that circulating red blood cells (RBC) 'report' surface properties of the vascular endothelium. To some extent, the RBC glycocalyx mirrors the endothelial glycocalyx. A poor (charge-deprived) endothelial glycocalyx causes a poor RBC glycocalyx and vice versa. This observation led to the assumption that the current state of an individual's vascular endothelium in terms of electrical surface charges and sodium-buffering capabilities could be read simply from a blood sample. Recently, a so-called salt blood test was introduced that quantifies the RBC sodium buffer capacity and thus characterizes the endothelial function. The arguments are outlined in this article spanning a bridge from cellular nano-mechanics to clinical application.
    MeSH term(s) Biological Transport/physiology ; Cell Membrane Permeability/physiology ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Erythrocytes/metabolism ; Erythrocytes/pathology ; Extracellular Space/metabolism ; Glycocalyx/metabolism ; Humans ; Hypertension/metabolism ; Hypertension/pathology ; Hypertension/physiopathology ; Sodium/metabolism ; Sodium Chloride/pharmacokinetics
    Chemical Substances Sodium Chloride (451W47IQ8X) ; Sodium (9NEZ333N27)
    Language English
    Publishing date 2014-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gft461
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  4. Article ; Online: Vascular endothelium leaves fingerprints on the surface of erythrocytes.

    Oberleithner, Hans

    Pflugers Archiv : European journal of physiology

    2013  Volume 465, Issue 10, Page(s) 1451–1458

    Abstract: Gliding of red blood cells (RBC) through blood vessels is mediated by the negatively charged glycocalyx located on the surfaces of both RBC and endothelial cells (EC). In various vasculopathies, EC gradually lose this protective surface layer. As a ... ...

    Abstract Gliding of red blood cells (RBC) through blood vessels is mediated by the negatively charged glycocalyx located on the surfaces of both RBC and endothelial cells (EC). In various vasculopathies, EC gradually lose this protective surface layer. As a consequence, RBC come into close physical contact with the vascular endothelium. It is hypothesized that the RBC glycocalyx could be adversely affected by a poor EC glycocalyx. This hypothesis was tested by evaluating the RBC and EC surface layers with atomic force microscopy techniques. In the first series of experiments, EC monolayers grown in culture were exposed to rhythmic drag forces exerted from a blood overlay (drag force treatment), and thereafter, the EC surface was investigated in terms of thickness and adhesiveness. In the second series, the glycocalyx of the EC monolayers was disturbed by enzymatic cleavage of negatively charged heparan sulfates before drag force treatment, and thereafter, the RBC surface was evaluated. In the third series, the RBC glycocalyx of the blood overlay was enzymatically disturbed before drag force treatment, and thereafter, the EC surface was evaluated. A strong positive correlation between the RBC and EC surface properties was found (r (2) = 0.95). An enzymatically affected EC glycocalyx lead to the shedding of the RBC glycocalyx and vice versa. It is concluded that there is physical interaction between the blood and endothelium. Apparently, the RBC glycocalyx reflects properties of the EC glycocalyx. This observation could have a significant impact on diagnosis and treatment of cardiovascular diseases.
    MeSH term(s) Cell Line ; Cells, Cultured ; Endothelial Cells/metabolism ; Endothelial Cells/ultrastructure ; Endothelium, Vascular/cytology ; Endothelium, Vascular/metabolism ; Erythrocyte Membrane/metabolism ; Erythrocyte Membrane/ultrastructure ; Erythrocytes/metabolism ; Erythrocytes/ultrastructure ; Glycocalyx/metabolism ; Heparitin Sulfate/metabolism ; Humans
    Chemical Substances Heparitin Sulfate (9050-30-0)
    Language English
    Publishing date 2013-05-11
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-013-1288-y
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  5. Article ; Online: Two barriers for sodium in vascular endothelium?

    Oberleithner, Hans

    Annals of medicine

    2012  Volume 44 Suppl 1, Page(s) S143–8

    Abstract: Vascular endothelium plays a key role in blood pressure regulation. Recently, it has been shown that a 5% increase of plasma sodium concentration (sodium excess) stiffens endothelial cells by about 25%, leading to cellular dysfunction. Surface ... ...

    Abstract Vascular endothelium plays a key role in blood pressure regulation. Recently, it has been shown that a 5% increase of plasma sodium concentration (sodium excess) stiffens endothelial cells by about 25%, leading to cellular dysfunction. Surface measurements demonstrated that the endothelial glycocalyx (eGC), an anionic biopolymer, deteriorates when sodium is elevated. In view of these results, a two-barrier model for sodium exiting the circulation across the endothelium is suggested. The first sodium barrier is the eGC which selectively buffers sodium ions with its negatively charged proteoglycans. The second sodium barrier is the endothelial plasma membrane which contains sodium channels. Sodium excess, in the presence of aldosterone, leads to eGC break-down and, in parallel, to an up-regulation of plasma membrane sodium channels. The following hypothesis is postulated: Sodium excess increases vascular sodium permeability. Under such conditions (e.g. high-sodium diet), day-by-day ingested sodium, instead of being readily buffered by the eGC and then rapidly excreted by the kidneys, is distributed in the whole body before being finally excreted. Gradually, the sodium overload damages the organism.
    MeSH term(s) Blood Pressure ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Glycocalyx/metabolism ; Homeostasis ; Humans ; Permeability ; Sodium/blood ; Sodium/pharmacokinetics ; Sodium/pharmacology ; Sodium Channels/metabolism
    Chemical Substances Sodium Channels ; Sodium (9NEZ333N27)
    Language English
    Publishing date 2012-04-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1004226-x
    ISSN 1365-2060 ; 1651-2219 ; 0785-3890 ; 1743-1387
    ISSN (online) 1365-2060 ; 1651-2219
    ISSN 0785-3890 ; 1743-1387
    DOI 10.3109/07853890.2011.653397
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  6. Article ; Online: A physiological concept unmasking vascular salt sensitivity in man.

    Oberleithner, Hans

    Pflugers Archiv : European journal of physiology

    2012  Volume 464, Issue 3, Page(s) 287–293

    Abstract: About one third of the population worldwide is supposed to be salt sensitive which is a major cause for arterial hypertension later in life. For preventive actions it is thus desirable to identify salt-sensitive individuals before the appearance of ... ...

    Abstract About one third of the population worldwide is supposed to be salt sensitive which is a major cause for arterial hypertension later in life. For preventive actions it is thus desirable to identify salt-sensitive individuals before the appearance of clinical symptoms. Recent observations suggest that the vascular endothelium consists of two salt-sensitive barriers in series, the glycocalyx that buffers sodium and the endothelial cell membrane that contains sodium channels. Glycocalyx sodium buffer capacity and sodium channel activity are conversely related to each other. For proof of concept, a so-called salt provocation test (SPT) was developed that should unmask vascular salt sensitivity in humans at virtually any age. Nineteen healthy subjects, ranging from 25 to 63 years of age, underwent two series of 1-h blood pressure measurements after acute ingestion of a salt cocktail with or without addition of a sodium channel blocker effective in vascular endothelium. Differential analysis of the changes in diastolic blood pressure (net ∆DP) identified 12 individuals (63%) as being salt resistant (net ∆DP = -0.05 ± 0.62 mmHg) and seven individuals (37%) as being salt sensitive (net ∆DP = +6.98 ± 0.75 mmHg). Vascular salt sensitivity was not related to the age of the study participants. It is concluded that the SPT could be useful for identifying vascular salt sensitivity in humans already early in life.
    MeSH term(s) Adult ; Age Factors ; Blood Pressure/drug effects ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/physiology ; Epithelial Sodium Channel Blockers/pharmacology ; Female ; Humans ; Male ; Middle Aged ; Salt Tolerance/physiology ; Sodium Chloride/blood ; Sodium Chloride/pharmacology
    Chemical Substances Epithelial Sodium Channel Blockers ; Sodium Chloride (451W47IQ8X)
    Language English
    Publishing date 2012-06-29
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-012-1128-5
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  7. Article: Nanophysiology: fact or fiction?

    Oberleithner, Hans

    Pflugers Archiv : European journal of physiology

    2008  Volume 456, Issue 1, Page(s) 1–2

    MeSH term(s) Animals ; Cell Physiological Phenomena ; Cells/cytology ; Cells/ultrastructure ; Humans ; Microscopy, Atomic Force/trends
    Language English
    Publishing date 2008-02-01
    Publishing country Germany
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-008-0464-y
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  8. Article ; Online: Salt Sensitivity Determined From Capillary Blood.

    Oberleithner, Hans / Wilhelmi, Marianne

    Kidney & blood pressure research

    2016  Volume 41, Issue 4, Page(s) 355–364

    Abstract: Background/aims: A significant rise of blood pressure in response to a given salt load is a weak indication of high salt sensitivity, supposed to foster the development of arterial hypertension and related diseases in later life. In search of an ... ...

    Abstract Background/aims: A significant rise of blood pressure in response to a given salt load is a weak indication of high salt sensitivity, supposed to foster the development of arterial hypertension and related diseases in later life. In search of an alternative method we recently developed the salt blood test (SBT), a new concept for quantifying salt sensitivity (SS). Based on this concept, namely that red blood cells (RBC) report on salt sensitivity, the SBT-mini was developed.
    Methods: The SBT-mini utilizes a droplet of capillary blood mixed with a 'smart' Na+ cocktail. Red blood cells (RBC) of this mixture are allowed to sediment by gravity in a glass tube. SS is quantified by measuring RBC sedimentation rate. 90 healthy volunteers (39 males, 51 females; mean age: 23±0.5 years) were evaluated and 'standard values' for males and females were derived.
    Results: Sodium buffer capacity of female blood is about 20 % smaller as compared to male blood due to the lower hematocrit of females. SS of an individual is related to the mean standard value (set to 100 %) of the respective male/female cohort. High SS (> 120 %) has been found in 31 % of males and 28 % of females.
    Conclusions: SS can be estimated derived from the individual RBC sodium buffer capacity as measured by the SBT-mini. About one third of a healthy test cohort exhibits a high sensitivity to salt. Reduction of sodium consumption to at least two grams per day (equals five grams of NaCl per day as suggested by the WHO) is recommended, particularly for individuals with high salt sensitivity.
    MeSH term(s) Blood Pressure/drug effects ; Blood Sedimentation/drug effects ; Erythrocytes/drug effects ; Female ; Humans ; Hypertension/prevention & control ; Male ; Sodium Chloride, Dietary/pharmacology ; Young Adult
    Chemical Substances Sodium Chloride, Dietary
    Language English
    Publishing date 2016
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1326018-2
    ISSN 1423-0143 ; 1420-4096
    ISSN (online) 1423-0143
    ISSN 1420-4096
    DOI 10.1159/000443438
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  9. Article ; Online: Salty stories.

    Kurtz, Armin / Oberleithner, Hans

    Pflugers Archiv : European journal of physiology

    2015  Volume 467, Issue 3, Page(s) 443

    MeSH term(s) Animals ; Humans ; Sodium Chloride, Dietary/adverse effects ; Sodium Chloride, Dietary/metabolism ; Water-Electrolyte Balance
    Chemical Substances Sodium Chloride, Dietary
    Language English
    Publishing date 2015-03
    Publishing country Germany
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-015-1691-7
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  10. Article: Is the vascular endothelium under the control of aldosterone? Facts and hypothesis.

    Oberleithner, Hans

    Pflugers Archiv : European journal of physiology

    2007  Volume 454, Issue 2, Page(s) 187–193

    Abstract: Fluid and electrolyte balance in the human organism is controlled by aldosterone, a mineralocorticoid hormone of the suprarenal glands. The major target cells are localized in the kidney where the hormone controls transepithelial salt transport. Over the ...

    Abstract Fluid and electrolyte balance in the human organism is controlled by aldosterone, a mineralocorticoid hormone of the suprarenal glands. The major target cells are localized in the kidney where the hormone controls transepithelial salt transport. Over the past few years, evidence has been accumulated that cells of the cardiovascular system are also targeted by the hormone. As an example, endothelial cells resemble similar mechanisms triggered by aldosterone as shown for the kidney. Although the pathological alterations induced by aldosterone excess are obvious, the physiological changes are largely unknown. On the basis of recent experiments, using atomic force microscopy as an imaging tool and a mechanical sensor, I present a hypothesis on the physiological role of aldosterone in endothelial function and its potential implications in the control of blood pressure.
    MeSH term(s) Aldosterone/pharmacology ; Aldosterone/physiology ; Animals ; Blood Pressure/physiology ; Cell Shape/drug effects ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiology ; Humans ; Models, Biological ; Nitric Oxide/metabolism ; Sodium/metabolism ; Water-Electrolyte Balance/physiology
    Chemical Substances Nitric Oxide (31C4KY9ESH) ; Aldosterone (4964P6T9RB) ; Sodium (9NEZ333N27)
    Language English
    Publishing date 2007-05
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-007-0205-7
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