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

Pregnancy-induced hypertension may be linked with sodium pump inhibition and an increase in vascular myocytic tone and, hence, flow impedance. All of the findings of studies on circulating plasma and blood cells are not, however, consistent with this hypothesis. We therefore assessed sodium pump numbers and cation transport in lymphocytes from 23 women with untreated pregnancy-induced hypertension, 28 normotensive pregnant women and 28 healthy non-pregnant women. We measured the maximum 3H-ouabain binding capacity to determine the sodium pump activity and the apparent dissociation constant (the reciprocal of which estimates binding affinity) by Scatchard analysis, ouabain-sensitive (pump-mediated) 86rubidium influx and ouabain-resistant (pump-independent) influx in lymphocytes in vitro. Pregnant women, whether normotensive or hypertensive, had significantly more sodium pump activity and a higher pump-mediated and pump-independent 86rubidium influx than non-pregnant women. Sodium pump activity and the pump-mediated and pump-independent 86rubidium influx all reached normal, non-pregnant levels in normotensive pregnant women 6 weeks after delivery, but remained high in women with pregnancy-induced hypertension. The normotensive and hypertensive pregnant women and non-pregnant women all had similar ouabain binding affinity. The results of our study do not support the circulating sodium pump inhibitor hypothesis in pregnancy-induced hypertension.
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PMID:Sodium pump numbers and cation transport of lymphocytes in pregnancy-induced hypertension. 217 75

We have studied sodium potassium ATPase activity, the effect of endogenous plasma on sodium pump activity, potassium permeability and intracellular sodium and potassium concentrations in normotensive subjects without (n = 36) and with (n = 33) a positive family history of hypertension, and in patients with untreated essential hypertension (n = 52). Sodium pump activity was studied as ouabain sensitive uptake of rubidium 86 in washed red blood cells, incubated in an artificial medium closely resembling the anorganic constituents of plasma. Any influence of endogenous plasma on sodium pump activity was investigated by re-incubating the washed red blood cells in their own plasma and comparing ouabain sensitive rubidium uptake in the two media. To correct for any possible differences in external potassium concentration, a function for the relation between extracellular potassium concentration and absolute transport rates was derived experimentally. From this, actual transport rates in plasma were corrected by computer to an extracellular potassium concentration of 4.0 mmol/l. Sodium pump activity, concentration of circulating sodium transport inhibitor, potassium permeability and intracellular electrolytes were not statistically different in subjects with and without a positive family history of hypertension. Hypertensives had significantly raised sodium pump activity in artificial medium, but not when red cells were re-incubated in their own plasma. Thus, endogenous plasma inhibited the sodium pump by between 12% and 15%. Hypertensives also had a significantly raised potassium permeability. Potassium permeability and sodium pump activity were correlated significantly. Intracellular sodium concentrations were similar in normotensives and hypertensives, but the later showed a significantly lower intracellular potassium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Raised sodium pump activity and a circulating sodium transport inhibitor demonstrated on red blood cells of patients with untreated essential hypertension: correlation of pump activity with potassium permeability. 298 7

Sodium pump activity of blood vessels has been reported to decrease in several animal models of hypertension. We studied sodium-potassium-adenosine triphosphatase (Na-K-ATPase) activity of renal tubular segments in 12-week-old spontaneously hypertensive rats and in age-matched Wistar-Kyoto normotensive rats. The enzyme activity of the individual nephron segments was determined by a microfluorometric assay in which ATP hydrolysis is coupled with NADH oxidation. In the spontaneously hypertensive rats, systolic blood pressure was significantly higher (181 +/- 3 mm Hg) than in the Wistar-Kyoto rats (134 +/- 2 mm Hg). However, there was no difference in mean Na-K-ATPase activity in any of the nephron segments from the spontaneously hypertensive compared with the Wistar-Kyoto group. It is concluded that Na-K-ATPase activity does not change in any of the nephron segments with spontaneous hypertension.
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PMID:Sodium-potassium-adenosine triphosphatase in nephron segments of spontaneously hypertensive rats. 298 96

Essential hypertension is fundamentally a genetic disease which emerges because of environmental impact. The genetic factors involve intracellular abnormalities which affect calcium metabolism within smooth muscle cells and possibly within the heart and sympathetic nervous system. These abnormalities are influenced by one or more proteins of which calmodulin is a candidate. Sodium pump abnormalities may be primary but may be secondary feedback effects. Homeostasis keeps the blood pressure and cardiac function normal, but eventually becomes less effective. Such homeostasis is produced by negative feedback, but positive external factors also influence the eventual results. Gross homeostasis is provided by the baroreceptors, the renin-angiotensin-aldosterone system, etc. The malfunction of any one or any combination of these systems may produce or accelerate hypertension. Hyperplasia and hypertrophy of arteriolar smooth muscle play their role but also multiply the genetic cellular defects. It is possible that in the early history of man essential hypertension had an advantage which now has become obsolete because normotensive man's potential lifespan has been increased by modern civilization.
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PMID:The relation of genetics to essential hypertension: a review. 713 17

Decreased activity of the electrogenic sodium pump of vascular smooth muscle has been reported in several forms of experimental hypertension and may play an important role in basic disease mechanisms. It has been proposed that such pump suppression may characterize volume-expanded forms of hypertension. The present investigation tested this latter hypothesis. Sodium pump activity was assessed in vitro in sodium-loaded tail artery and thoracic aorta freshly excised from Dahl salt-sensitive (S) and salt-resistant (R) rats on low (0.4%) or high (8%) NaCl diets for 5 to 7 weeks. Rubidium (86Rb) uptake in the absence (total uptake) and presence (ouabain-insensitive uptake) of 1.0mM ouabain was measured and ouabain-sensitive uptake (nmole/mg dry weight/10 min) was calculated. In S rats, salt feeding was accompanied by elevation of arterial pressure, cardiac hypertrophy, increases of 20% to 30% in total blood volume, and increases in the ouabain-sensitive, ouabain-insensitive, and total uptakes in the aorta, but no significant change in uptakes in the tail artery. However, ouabain-sensitive uptake in the tail artery of all S rats exceeded than in R rats. There was no evidence of a decrease in vascular sodium pump activity accompanying hypertension in either artery. Therefore, the results of this study provide no evidence in support of the hypothesis that pump suppression in vascular smooth muscle characterizes volume-expanded forms of hypertension. It is unlikely that the observed increases in vascular pump activity in S rats reflected intracellular sodium concentrations higher than those in the control rats. Rather, increases in the numbers of pump molecules or in their turnover rate are probably involved.
Hypertension
PMID:Sodium pump activity in arteries of Dahl salt-sensitive rats. 725 Oct 90

Normal aging is associated with different changes in the cardiovascular system that lead to an increase in pathological processes, such as hypertension, coronary artery disease, heart failure, and postural hypotension with enhancement of both morbidity and mortality. The vascular alterations consist of changes in the function and structure of the arteries, and increasing vascular stiffness, mainly when atherosclerosis is present, whose incidence is increased with age. The arteries accumulate lipids, collagen, and minerals. Cerebral perfusion may be reduced in the elderly, mainly regional cerebral blood flow, which leads to a deterioration of mental and physical functions. The degree of deterioration is increased when aging is associated with hypertension. Aging alters endothelial cells, which play an important role in vascular tone regulation. Such a process tends to reduce endothelium-dependent relaxations, and clearly reduces the vasodilation elicited by beta-adrenoceptor agonists. The contractions induced by different agents, such as 5-hydroxytryptamine, histamine, high potassium and angiotensin are barely affected with aging, whereas those elicited by noradrenaline or endothelin are usually reduced. However, plasma noradrenaline levels are increased with age, mainly due to a reduction in the sensitivity of presynaptic alpha 2-adrenoceptors and also of noradrenaline uptake. Sodium pump activity, that controls cellular ionic homeostasis, may be altered depending on animal species. Finally, vascular Ca2+ regulation appears to be altered and the extracellular Ca2+ dependence of contractile responses elicited by agonists is increased, which justifies the enhanced sensitivity to Ca2+ antagonists in senescence.
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PMID:Age-related changes in vascular responses: a review. 761 68

Although volume and vasoconstriction have been considered polar elements in a useful pathogenetic hypertension model, many observations suggest that vasoconstriction is involved in volume-dependent hypertension, reflecting the effect of a digitalis-like factor. To examine that possibility, we assessed the depressor responses to Digibind, an antibody Fab directed against digoxin, in a volume-dependent model--DOCA-salt-induced hypertension in rats. Digibind (10 mg/kg, intravenously) induced a gradual blood pressure fall over 2 h that was sustained for 4 h (P < .001). Blood pressure did not fall with Digibind when DOCA was administered without salt or a high-salt intake was provided without DOCA. The intracellular sodium content of the rat aorta, measured by atomic absorption spectroscopy after cold choline wash, was increased in the DOCA-high-salt rats (23.3 +/- 2.7 mEq/L) compared to control rats (12.1 +/- 0.8 mEq/L; P < .001). Aorta sodium content, in parallel with blood pressure, was not increased either by dietary salt supplementation without DOCA, or by DOCA with a low-salt diet. Sodium pump activity was measured as 86Rb uptake into vascular smooth muscle (VSM). Both ouabain-sensitive and ouabain-resistant 86Rb uptake were significantly higher in VSM from DOCA-high-salt animals (P < .01). Despite its effectiveness in reducing blood pressure in this model, Digibind influenced neither VSM sodium content nor 86Rb uptake. The results are consistent with a role for a circulating digitalis-like factor in this volume-dependent model, but events at the VSM level are complex.
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PMID:Volume sensitive hypertension and the digoxin-like factor. Reversal by a Fab directed against digoxin in DOCA-salt hypertensive rats. 854 Oct 8

We have previously demonstrated that vascular sodium pump activity is stimulated in several rat models of hypertension. In addition, others have reported an upregulation of mRNA for the Na+,K+-ATPase alpha1-subunit in hypertension. To test the effect of sustained, cyclic, stretch-relaxation stimuli on the expression of alpha1- and alpha2-subunits of Na+,K+-ATPase in vascular smooth muscle cells, we used the Flexercell strain unit to stretch rat aortic smooth muscle cells for several days on a collagen-coated silicone elastomer substratum. Six-second cycles of stretch-relaxation were applied to obtain 10% average surface elongation (22% maximum) for 4 days. Control cells were not stretched but were grown on a similar surface. The effect of Gd3+, a blocker of stretch-activated channels, was also investigated. At the end of 4 days, protein expression of alpha1- and alpha2-subunits was determined by Western blot analysis. Intensity of the bands for alpha1- and alpha2-subunits was quantified with the use of a computerized image analyzer. In the stretched cells, both the alpha1- and the alpha2-subunit protein-band intensities were significantly increased compared with those of the non-stretched cells. Treatment with 50 micromol/L Gd3+ during the application of stretch prevented the upregulation of alpha2-expression but not that of alpha1-expression. Sodium pump activity, the functional counterpart of Na+,K+-ATPase, was inhibited as a result of stretch; Gd3+ had no effect on this variable. Our results suggest that in vascular smooth muscle, stretch may be a signal for the upregulation of both the alpha1- and alpha2-isoforms. However, a differential response of the two isoforms to the blocker of stretch-activated channels implies involvement of different mechanisms. This alteration in protein expression is not reflected in the function of the enzyme.
Hypertension 1996 Mar
PMID:Regulation of Na+,K+-ATPase alpha-subunit expression by mechanical strain in aortic smooth muscle cells. 861 48

Angiotensin (Ang) II stimulates secretions of aldosterone and an endogenous ouabain-like steroid (EO) from bovine adrenal zona glomerulosa (BAG) cells. The BAG cell sodium pump, a possible target of EO, affects aldosterone secretion although little is known about this pump. Here, we describe the effects of Ang II on the characteristics of this transporter and steroid secretions. Under serum-free conditions, 3H-ouabain bound to a single class of sites on BAG cells. Binding of label was time and concentration dependent, was sensitive to extracellular potassium ions, and was displaced by ouabain and digoxin with EC50 of approximately 218 and approximately 232 nmol/L, respectively. Sodium pump-mediated 86Rb uptake was inhibited by ouabain (EC50 approximately 301 nmol/L). Ang II dose dependently augmented secretions of EO and aldosterone, increased ouabain-sensitive 86Rb uptake and 3H-ouabain binding, and increased the affinity for 3H-ouabain binding (Kd, from 205 to 80 nmol/L) with no change in the maximal number of sodium pumps (5.45x10(6)) per cell. Losartan blocked all effects of Ang II except EO secretion, which was inhibited by PD123319. We conclude that BAG cells express sodium pumps in high density and bind ouabain to a single class of low-affinity sites. The characteristics of the sodium pumps protect BAG cells from EO autotoxicity but may exclude them from mediating feedback inhibition of EO secretion. The effects of Ang II on sodium pump activity, ouabain binding affinity, and aldosterone secretion are mediated via Ang II type 1 receptors, whereas Ang II type 2 receptors augment EO secretion. The role of the Ang II-mediated increase in the ouabain sensitivity of BAG cell sodium pumps in the secretions of aldosterone and EO remains to be elucidated.
Hypertension 1999 Jan
PMID:Effects of angiotensin II on sodium potassium pumps, endogenous ouabain, and aldosterone in bovine zona glomerulosa cells. 993 Nov 32

Dahl salt-sensitive rats (DS), which have a mutation in the alpha-1 subunit of Na(+)/K(+)-ATPase, exhibit impaired pressure natriuresis and on a high-salt diet, retain Na(+) and exhibit increased blood pressure. Recently, we have shown that mammalian tissues contain a bufadienolide Na(+)/K(+)-ATPase inhibitory factor, marinobufagenin (MBG), that exhibits greater affinity for the alpha-1 than alpha-3 sodium pump isoform. The present study investigated the possible role of MBG in hypertension in DS on a high NaCl intake. Eight DS and 8 Dahl salt-resistant rats (DR) were placed on an 8% NaCl diet. Within 2 weeks, systolic blood pressure increased in DS (162+/-9 mm Hg at week 2 versus 110+/-2 mm Hg in baseline, P<0.01), and increased less in DR (124+/-3 mm Hg at week 2 versus 112+/-2 mm Hg in baseline). Renal excretion of MBG increased 4-fold (38.9+/-7.6 pmol versus 9.1+/-1.3 pmol in baseline, P<0.01) in DS, but by only 25% in DR (13.2+/-0.9 pmol versus 10.3+/-0.7 pmol in baseline). Excretion of endogenous ouabain did not change in either strain. MBG-immunoreactive material was purified from the urine of hypertensive DS by means of 2 steps of reverse-phase high performance liquid chromatography (HPLC) and compared with plant ouabain and amphibian MBG for its ability to inhibit the Na(+)/K(+)-ATPase from rat kidney (which expresses only alpha-1 Na(+)/K(+)-ATPase isoform). Unlike ouabain (IC(50)=248 micromol/L), serially diluted, HPLC-purified MBG immunoreactivity from DS and authentic MBG potently inhibited rat kidney Na(+)/K(+)-ATPase (IC(50)=70 and 78 nmol/L, respectively). Our results suggest that an alpha-1 Na(+)/K(+)-ATPase ligand, MBG, is elaborated to promote natriuresis in hypertensive DS. MBG acts as a selective inhibitor of the ouabain-resistant alpha-1 Na(+)/K(+)-ATPase subunit, ie, the major sodium pump isoform of the kidneys, as would be expected of a putative natriuretic hormone.
Hypertension 2001 Feb
PMID:Marinobufagenin, an endogenous alpha-1 sodium pump ligand, in hypertensive Dahl salt-sensitive rats. 1123 Mar 19


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