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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The number of sodium pump sites on erythrocytes was measured on 1,847 individuals in 80 Utah kindreds ascertained through probands with cardiovascular disease. Likelihood analysis supported recessive inheritance of high pump number. The major locus explained 14.0% of the variance in pump number; polygenic inheritance explained another 63.4%. Homozygotes for the recessive allele occurred with a frequency of 1.74% and had a mean pump number estimated as 566.0 sites/red blood cell (RBC) versus a mean of 312.2 sites/RBC for the other genotypes. Young individuals with the high pump number genotype were leaner, and older adults with the high pump number genotype were heavier. Diabetes and early hypertension were more prevalent in women with the high pump number genotype. Although not significant, obesity in adults of both sexes and early coronary heart disease in men were more prevalent in individuals with the high pump number genotype.
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PMID:Recessive inheritance of a high number of sodium pump sites. 255 21

In this review, we first summarize the evidence which indicates that the inability of the kidney to excrete salt and water normally, particularly when combined with increased salt intake, is frequently associated with hypertension. We then concentrate on the link between sodium and water retention and hypertension. The increase in blood pressure probably results from the increase in volume rather than from the increase in salt. Recent evidence suggests that an increase in volume in the lesser circulation stimulates the release of a sodium pump inhibitor, probably the putative natriuretic hormone, from the hypothalamus. This agent appears to affect cardiac and vascular smooth muscle by suppressing Na+,K+-ATPase, and hence Na+-K+ pump activity in both muscle cells and adrenergic nerve terminals. The sodium pump inhibitor is a heat stable small molecule but its chemical structure is still unknown. It is clearly different from atrial natriuretic factor. We conclude the review with speculations on the possible role of renotropin and various growth and growth inhibitory factors in the vascular structural changes.
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PMID:The kidney in the pathogenesis of hypertension: the role of sodium. 258 44

Leucocyte sodium content and sodium pump activity was studied in overweight and lean hypertensive subjects and normotensive controls, all in the fasting state. In lean subjects (body mass index less than 27 kg m-2), hypertensives did not have altered leucocyte sodium content or pump activity. In the overweight (mostly obese) subjects, the leucocyte sodium content was higher in hypertensive than in normotensive subjects (median (range) 56.1 (42.0-84.1) vs 32.0 (18.2-59.4) mmol kg-1, P less than 0.001). This raised sodium content in overweight hypertensives was associated with a lower (ouabain-sensitive) 22Na efflux rate constant (2.25 (1.15-3.01) vs 2.64 (1.98-3.61) h-1, P less than 0.05) and a higher passive (or ouabain-insensitive) 22Na efflux rate constant (0.90(0.53-1.18) vs 0.63 (0.21-1.09) h-1, P less than 0.01). The systolic and diastolic blood pressures were significantly correlated to intracellular Na+ in the overweight group (r = 0.41 and 0.56, P less than 0.02 and 0.001 respectively). Thus, hypertension in the overweight subjects is associated with accumulation of intracellular sodium that may be due to abnormalities of the active sodium pump, though changes in ouabain-insensitive mechanisms also occur.
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PMID:Leucocyte sodium content and sodium pump activity in overweight and lean hypertensives. 261 17

The mechanisms that define the relation between blood pressure and sodium handling are not yet well understood. Although several abnormalities in sodium transport have been associated with hypertension, a link between the blood pressure of normotensive subjects and the erythrocyte sodium-potassium adenosine triphosphatase pump, the principal sodium transporter of sodium, has not been previously demonstrated. Data from independent measurements of erythrocyte intracellular sodium, ouabain-sensitive sodium efflux, and the number of sodium pump sites per red blood cell were used to calculate a second-order rate constant for ouabain-sensitive sodium efflux. Among 20 normotensive white subjects, this rate constant correlated significantly (p less than 0.005) with mean arterial blood pressure. A significant correlation was not observed between the rate constant and the blood pressure of 22 hypertensive subjects. A hypothesis is proposed, which suggests that the sodium efflux rate constant of erythrocytes is related to the control of sodium reabsorption via the sodium pump of the renal tubules and that an elevated erythrocyte rate constant may be associated with chronic increased sodium reabsorption, which leads to volume expansion and the development of hypertension.
Hypertension 1989 Jun
PMID:Erythrocyte sodium transport and blood pressure in white subjects. 266 27

This review considers in some detail the hypothetical relationships between sodium fluxes, both active and passive, across the cell membrane, and intracellular sodium concentration in vascular smooth muscle in the animal models of hypertension. It appears that two basic types of transport defects, increased cell membrane permeability to sodium and decreased active pumping of sodium at a given internal sodium concentration, can exist in vascular smooth muscle in experimental hypertension, and that sometimes the two defects coexist, further increasing internal sodium concentration. It is possible that eventually we may find similar transport defects in vascular smooth muscle in humans with arterial hypertension. Decreased active pumping at a given internal sodium concentration appears to result from a humoral sodium pump inhibitor. Future directions for research in the area are also considered. First priority should be given efforts to determine the chemical structure of the sodium pump inhibitor(s). High priority should also be given to attempts to measure passive and active sodium fluxes and intracellular sodium concentration in vascular smooth muscle cells in vivo, and to determine the role of atrial natriuretic factor in the genesis and maintenance of hypertension.
Hypertension 1987 Nov
PMID:Pathophysiological role of cation transport and natriuretic factors in hypertension. 282 58

Plasma from volume-expanded and salt-loaded hypertensive animals and from patients with essential hypertension has been reported to inhibit Na+, K+-adenosine triphosphatase (ATPase). Inhibition of the sodium pump in vascular smooth muscle caused by such a circulating factor could increase vascular tone and sensitivity to vasoactive agents, and thereby result in arterial hypertension. Numerous efforts in the past failed to isolate the putative factor from urine and plasma. Recent studies have suggested that the hypothalamus is an important source of an endogenous Na+, K+-ATPase inhibitor, but its isolation from the tissue extracts has been rendered difficult by the presence of other cellular constituents that cause artifactual interference with the assays and purification procedures. Using an alternative approach of isolating the inhibitor from culture medium, we found that dispersed fetal rat hypothalamic neurons in a capillary culture system release a heat-stable, peptidic, low-molecular-weight, active sodium transport inhibitor that causes a reversible increase in vascular tone, sensitizes vascular smooth muscle to the vasoactive effect of norepinephrine, and possesses several characteristics of the putative endogenous digitalislike factor. This inhibitor may be a chemical mediator linking kidney, brain, and cardiovascular system in the genesis of experimental volume-expanded and salt-loaded hypertension and human essential hypertension.
Hypertension 1987 Nov
PMID:Problems and pitfalls in the isolation of an endogenous Na+, K+-ATPase inhibitor. 282 67

This review summarizes our bioassay methods for determining the level of humoral sodium pump inhibiting factor after acute volume expansion in experimental animals and humans, and in low renin experimental and human essential hypertension. In brief, ouabain-sensitive 86Rb uptake and membrane potential in blood vessels from normal animals are measured after incubation in plasma supernate from experimental subjects and animals and their respective controls. The data show that humoral sodium pump inhibitor is elevated after acute volume expansion in normal animals (dogs and rats) and in normal humans. The level of inhibitor is also elevated in patients with low renin essential hypertension and in experimental animals with low renin, volume-dependent types of hypertension, namely, one-kidney, one wrapped hypertension in dogs, and one-kidney, one clip and reduced renal mass-saline hypertension in rats. Humoral sodium pump inhibiting factor inhibits the Na+-K+ pump in the cardiovascular system. Such inhibition by other means (hypokalemia, cardiac glycosides) activates the system. Therefore, we also discuss the possible role of humoral sodium pump inhibitor in low renin volume-dependent hypertension.
Hypertension 1987 Nov
PMID:Humoral sodium transport inhibitor in acute volume expansion and low renin hypertension. 282 71

The possibility that endogenous inhibitors of the sodium pump exist and bind to the cardiac glycoside binding site on Na+,K+-adenosine triphosphatase (ATPase) has been a source of much controversy. Although numerous hormones and inorganic ions that modulate Na+,K+-ATPase activity have been described, most of these affect the sodium pump indirectly by varying the intracellular sodium concentration or by increasing the number of enzyme units. None of these endogenous compounds has been shown conclusively to modulate sodium pump activity by binding to the cardiac glycoside binding site on Na+,K+-ATPase. However, the near-universal presence of three high-affinity binding sites on the alpha-subunit of the enzyme has engendered much speculation that endogenous ligands for these receptors must exist. In addition, none of the hormones known to indirectly affect sodium pump activity in vivo has been shown to modulate Na+,K+-ATPase activity in response to extracellular volume expansion or to play a role in the pathogenesis of hypertension or chronic renal failure, conditions in which a circulating inhibitor of Na+,K+-ATPase has been implicated. This report presents a condensed history of the search for endogenous inhibitors of Na+,K+-ATPase and describes recent advances in the field. Despite progress in identifying and characterizing compounds that could affect Na+,K+-ATPase activity in vivo, definitive proof for the existence of endogenous ligands for the cardiac glycoside binding site remains elusive.
Hypertension 1987 Nov
PMID:Endogenous cardiac glycosidelike compounds. 282 72

The role of an endogenous sodium pump inhibitor in the pathogenesis of hypertension has been reported in several papers. Unfortunately, because of the unknown structure and lack of biochemical characterization, some discrepancies have arisen. In this study we report a method to obtain extracts from human plasma that are able to inhibit Na+/K+-ATPase in vitro. Preliminary characterization was carried out, which showed that the extracts are able to inhibit Na+/K+-ATPase, pNPPase, and [3H]ouabain binding to red blood cells. The enzyme inhibition is not due to vanadate, FFA, or bivalent cations, and it seems to be reversible, dose-dependent, and largely prevented in E1 conformation of the enzyme. These results seem to support the hypothesis that human plasma contains a sodium pump inhibitor with many characteristics of a "ouabainlike" compound.
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PMID:Characterization of a Na+/K+-ATPase inhibitor from human plasma: preliminary data. 284

These studies were designed to investigate whether alterations in the sodium transport could account for the enhanced transmitter release observed during sympathetic nerve stimulation in SHR. In the isolated in vitro perfused rat kidneys, norepinephrine (NE) storage sites were labelled with [3H]-NE and the transmitter overflow was evaluated at various frequencies during the periarterial nerve stimulation. Stimulus-induced transmitter overflow was consistently greater and the maximal overflow was 2-fold higher in the kidneys of SHR when compared to that of normotensive WKY. Addition of ouabain, a selective inhibitor of the sodium pump, (10(-3)M in the medium) significantly enhanced stimulus induced overflow in both the groups. However, the magnitude of these changes was significantly greater in WKY than in SHR kidneys suggesting that the membrane Na+-pump was functionally less efficient in the SHR. Ouabain virtually eliminated the differences between the two groups in that the transmitter overflow was essentially identical in SHR and WKY in the presence of the Na+-pump inhibitor. These observations suggest that a genetic abnormality in the neuronal sodium pump could account for the enhanced sympathetic transmitter overflow and contribute to hypertension in the spontaneously hypertensive rats.
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PMID:Abnormalities in the sodium transport as the causative factor for enhanced norepinephrine overflow in the spontaneously hypertensive rat. 284 15


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