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10th International Congress "Cell Volume Regulation: Novel Therapeutic Targets and Pharmacological Approaches"
SALT: IT'S DAMAGING EFFECT ON THE CARDIOVASCULAR SYSTEM MacGregor, G.
Wolfson Institute of Preventive Medicine, Barts and London School of Medicine and Dentistry, United Kingdom
There is overwhelming evidence that a reduction in our salt intake from the current level in most countries of 9-12 g/day down to 6 g/day i.e. a 50% reduction lowers blood pressure and thereby reduces the number of people dying and suffering from strokes, heart attacks and heart failure - the commonest cause of death and disability in the world. Increasing evidence now suggests that salt has a direct damaging affect on the vascular system by increasing arterial stiffness and impairing endothelial function. These effects may be independent and/or additive to the effect that salt has on blood pressure.
There is now increasing evidence that small changes in plasma sodium could play an important role. For instance, increasing sodium concentration within the physiological range has been shown to increase endothelial stiffness, reduce nitric oxide release as well as having a stimulant effect on some cell cultures.
Clinical studies have shown that every time salt is eaten, even in quite modest amounts, there are changes in
plasma sodium in the blood. These are associated with an adverse effect on the vascular system, increasing arterial stiffness and reducing endothelial function.
At the same time, studies in patients on hemodialysis have shown that small changes in the dialysis fluid sodium which result in changes in plasma sodium in the patients, do seem to affect blood pressure at least in the short term. These studies are leading to a better understanding of the mechanism whereby salt could affect not only blood pressure but also have direct effects on the vascular system.
Public health policies to get the food industry to slowly reduce the large amounts of salt they add to food have been successful in Finland, and are being successful in the UK. Every country should now adopt a coherent and workable strategy to reduce salt intake in the whole population. Even a modest reduction in population salt intake will have major beneficial effects on health, along with major cost-savings.
REGULATED EXPRESSION OF NA+/K+ PUMP DURING HUMAN BLOOD LYMPHOCYTE PROLIFERATION
Marakhova, I.I. and Mityushova, E.V.
Institute of Cytology RAS, Saint Petersburg, Russian Federation
The mitogenic effect of growth factors is mediated by the transcriptional regulation of numerous genes which control cell cycle progression and DNA replication. In addition, in order to realize the mitogenic signal into cell functional response, genes involved in proliferation-related biochemical and physiological processes are co-regulated. In this study we show that in mitogen-stimulated human blood lymphocytes, enhanced ouabain-sensitive Rb+(K+) fluxes in the middle/late stage of Gq/Gj/S transit are associated with the increase of the amount of Na+,K+ pumps expressed at the cell surface (as determined by the [3H]ouabain binding). Analysis of total RNA (RT-PCR) and protein abundance (Western blotting) showed a 3-fold increase in the level of Na+,K+-ATPase al- and pi-subunits mRNAs and significant increase in the Na+,K+-ATPase al-subunit protein during the first day of mitogen-induced proliferation. In competent T lymphocytes, recombined interleukin-2 (IL-2) was revealed
to increase both the transport activity of Na+/K+ pump and the content of Na+,K+-ATPase al-protein. The pharmacological inhibition of MEK/ERK or JAK/STAT cascades suppressed the IL-2-induced proliferation and reduced the functional and protein expressions of Na+,K+-ATPase. These results suggest that in mitogen-induced human blood lymphocytes (l) the functional expression of Na+/K+ pump is closely associated with the cell cycle progression, being dependent on IL-2; (2) the cell cycle-associated enhancement of K+ transport is a result of increased number of newly synthesized functioning Na+/K+ pumps in cell membrane; (3) the cytokine signaling via the IL-2 receptor is necessary for the upregulation of Na+/K+ pump during the lymphocyte transition from quiescence to proliferation.
This work was supported by MCB RAS program, SS program (4957.2012.4), RFBR (13-04-00234).
Бюллетень сибирской медицины, 2013, том 12, № 4, с. 24-68
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