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

The role of endogenous inhibitors of vascular Na,K-ATPase (NKA) activity in salt-induced hypertension was evaluated by examining the inhibition of 86Rb+ uptake in aortae of Sprague-Dawley (SD) rats by plasma derived from Dahl sensitive (DS) and resistant (DR) rats given high (8%) and low (0.4%) NaCl diet for four weeks. With 4 weeks of high salt diet DS rats demonstrated marked increase in systolic blood pressure. When compared to DR and DS rats on low salt diet, plasma from DR and DS rats on high salt diet had a stimulatory (not inhibitory) effect on NKA as measured by 86Rb+ uptake of SD rat aortae. As compared to DR rats plasma from DS rats on similar salt intakes had a stimulatory effect on NKA of SD rats. Aortae from the 4 groups of Dahl rats were also assayed for NKA activity. Total, ouabain-sensitive and ouabain-insensitive NKA activities were higher in DS rats as compared to DR rats on similar salt diet. Both DS and DR rats on high salt diet had higher NKA activity than on low salt diet. There was no evidence for a decrease in vascular sodium pump activity accompanying hypertension. Furthermore, high salt diet did not increase plasma Na,K-ATPase inhibitory activity in DS rats when hypertensive. These results suggest that NKA inhibition plays a minor role if any in hypertension of DS rats, in contrast to what has been hitherto believed.
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PMID:The role of vascular Na,K-ATPase activity in salt induced hypertension in Dahl rats. 284 88

Studies on the role of endogenous sodium pump inhibitors in hypertension have used ouabain, a Na,K-ATPase inhibitor, as a pharmacological probe to test the effect of direct vascular Na,K-ATPase inhibition in man. Previous work has suggested that there are no alpha-adrenoceptor mediated components in the vasoconstrictor effect of this drug, although several animal and in vitro studies have shown a complex interaction between ouabain and either sympathetic neurotransmission or alpha-adrenergic excitation-contraction coupling mechanisms. To re-examine this issue, we infused ouabain at 7 micrograms/dl per min for 20 min without (saline infusion) or with phentolamine (8.0 micrograms/dl per min for 15 min), an alpha-adrenoceptor blocking agent, in uncomplicated mild to moderate hypertensive patients. The drugs were infused into the brachial artery, and forearm blood flow (by strain-gauge plethysmography), systemic blood pressure and heart rate were measured concomitantly. After local phentolamine pretreatment, ouabain lost its vasoconstrictor effect (n = 5). This result is unlikely to have been related to vasodilation because histamine, a non-alpha-adrenergic vasodilator, infused in another group (n = 5) of patients at rates roughly equieffective to phentolamine (0.05 microgram/dl per min for 15 min) did not modify the vasoconstrictor action of ouabain. Thus alpha-adrenoceptor mediated components caused the forearm vascular effect of ouabain and must be taken into account when using ouabain to study endogenous sodium pump inhibitor(s) in human hypertension.
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PMID:Ouabain vasoconstricts human forearm arterioles through alpha-adrenergic stimulation. 285 45

Using long-term automatic blood pressure recording it has previously been shown that subjects with family history of hypertension show a minute fall of blood pressure during sodium restriction, which is reversible by high sodium intake. Thus normotensives with hypertensive antecedents as a group are salt-sensitive, whereas normotensives without heredity of hypertension as a group are salt-resistant. The present study compares intracellular sodium, potassium and calcium, sodium pump activity, NaK-cotransport of red blood cells and density and affinity of alpha 2-adrenergic receptors of platelets in normotensive subjects classified according to family history of hypertension and according to 'salt sensitivity' and 'salt resistance'. Neither the family history of hypertension nor salt sensitivity correlated with intracellular sodium, potassium, calcium, Na-pump activity and NaK-cotransport. Alpha 2-adrenergic density was higher in salt-sensitive than in salt-resistant subjects (P < 0.05) but similar in subjects with a positive and negative family history of hypertension. However, alpha 2-adrenergic receptor density decreased significantly during 2 weeks of moderate salt restriction from 169.6 +/- 34.2 to 142.6 +/- 30.8 (P < 0.01, paired t-test), which may explain the decreased pressor response to infused noradrenaline observed in a previous study during moderate salt restriction. It is concluded that in humans there is no association of genetic predisposition of hypertension or of salt sensitivity to an alteration of sodium pump activity, NaK-cotransport, intracellular sodium and calcium. Alpha 2-receptor density of platelets deserves further study as a possible predictor of salt sensitivity in normotensives.
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PMID:Salt sensitivity in normotensives with family history of hypertension: studies of membrane transport, intracellular electrolytes and alpha 2-adrenergic receptors. 285 19

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

The ability of plasma extracts to inhibit Na+-K+ ATPase in vitro (P.I.A.) was tested in 20 normotensives, 10 without (F-) and 10 with (F+) familial hypertension, in 20 borderlines (BL) and in 21 essential hypertensives (EH). In these subjects we also measured intralymphocytic sodium (ILSC) and potassium (ILKC) content, P.R.A. urinary aldosterone and Na+(Na+u), and blood pressure. P.I.A. of EH, BL and F+ subjects was significantly higher than that of F-. 60% of EH and BL and 40% of F+ had P.I.A. values greater than the highest found in F-. P.I.A. was significantly related to mean blood pressure (r = 0.63), to ILSC (r = 0.56), to ILKC (r = -0.56), to ILSC/ILKC ratio (r = 0.71) and to Na+u (r = 0.39) but not to P.R.A. or aldosterone. These data demonstrate that plasma extracts from young subjects prone to hypertension may inhibit sodium pump and that this inhibitor may affect blood pressure by altering the Na+/K+ intracellular ratio.
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PMID:Plasma Na+-K+ ATPase inhibitory activity in normal and hypertensive subjects: relationship to intracellular electrolytes and blood pressure. 299 Jul 69

High sodium intake in the presence of an intrinsic or acquired defect in renal sodium excretion will result in extracellular fluid volume (ECFV) expansion which is accompanied by decreased baroreceptor reflex sensitivity. We have shown that ECFV-expansion also stimulates the secretion of an endogenous inhibitor of the Na-K-ATPase enzyme and high activity of this sodium transport inhibitor was detected in plasma of patients with primary aldosteronism, the most classical type of volume-dependent hypertension. Thus, vasoconstriction due to inhibition of sodium pump activity of the vascular smooth muscle cell may contribute to the pathogenesis of human arterial hypertension. In analogy, ouabain (8.5 micrograms/kg) when administered i.v. to healthy volunteers inhibited RBC - Na-K-ATPase by 49% and significantly increased peripheral vascular resistance by 24 - 36%. The calcium entry blocker nifedipine (10 mg orally) completely prevented ouabain-induced vasoconstriction suggesting that the action of ouabain was mediated by a rise in intracellular calcium. High potassium intake partially abolished the vasoconstrictor effect of ouabain and also significantly increased baroreceptor reflex sensitivity. The results of these studies support the concept that inhibition of the sodium and potassium pump of vascular smooth muscle cells by a yet putative endogenous inhibitor of Na-K-ATPase (natriuretic hormone) may represent a crucial mechanism in the pathogenesis of at least certain forms of essential and secondary hypertension in man.
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PMID:The role of endogenous inhibition of Na-K-ATPase in human hypertension--sodium pump activity as a determinant of peripheral vascular resistance. 299 Jul 71

Based on oscillatory long-term blood pressure recordings and on biochemical findings in 62 normotensive and 54 untreated hypertensive subjects, who were investigated during their usual high sodium diet and after moderate salt restriction, we have developed a concept for the pathogenesis of essential hypertension, which differs from current concept proposed by others: We demonstrated that normotensive subjects with a positive family history of hypertension respond to sodium restriction from 200 to 50 mmol/day over 2 weeks with a minute fall of mean blood pressure of 2.9 +/- 0.7 mmHg (+/- SEM), whereas in subjects with a negative family history of hypertension blood pressure remained unchanged (-0.93 +/- 0.67 mmHg). This difference was only revealed by computing the "basal blood pressure average" from 240 heart beats, but not by conventional sphygmomanometric blood pressure measurements. Normotensives with heredity of hypertension or "salt sensitive" normotensive subjects were not different from subjects with a negative family history in the sodium pump, Na-K-cotransport or intracellular sodium and potassium of erythrocytes. In contrast, the former group had an increased sensitivity to infused noradrenaline, which might be responsible for enhanced tubular sodium reabsorption in subjects with a positive family history of hypertension (or "salt sensitive" subjects). We only found an increased K-permeability of red cells in established hypertension, which was compensated for by a an increased activity of the sodium pump. These cell membrane defects were more pronounced in more severe hypertension. In the course of essential hypertension a cell membrane defect may develop as a consequence rather than a cause of the disease.
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PMID:[Hereditary salt sensitivity as a cause of essential hypertension: studies of membrane transport and intracellular electrolytes]. 299 39

Erythrocyte membrane Na+,K+-ATPase activity was measured using a bioluminescence technique in 28 hypertensive patients (24 with essential hypertension, 2 with renovascular hypertension and 2 with hypertension secondary to primary hyperaldosteronism) and in 28 normotensive control subjects matched for age and sex. Erythrocyte Na+,K+-ATPase activity was significantly reduced in the patients with essential hypertension (130.9 +/- 11.4 vs. 186.6 +/- 19.5 nmol ATP/mg prot per h; mean values +/- SEM; p less than 0.05) and in the patients with secondary hypertension. A significant negative correlation was found between erythrocyte Na+,K+-ATPase and systolic blood pressure (r = -0.603; p less than 0.01), but not between Na+,K+-ATPase and plasma renin activity or plasma aldosterone levels. These data confirm the findings of a number of previous studies reporting reduced activity of erythrocyte Na+,K+-ATPase possibly related to the presence of a circulatory inhibitor of sodium pump. The method, based on ATP assay by bioluminescence, presents a high degree of specificity as well as simple, rapid execution.
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PMID:Measurement by bioluminescence technique of erythrocyte membrane Na+,K+-ATPase activity in hypertensive patients. 303 52

In recent years several different tests of cations in human cells have been studied to detect and to define possible roles in the development of essential hypertension. The goal of this report is to summarize what has been learned in genetic and epidemiological studies of human populations. The seven tests reviewed in greatest detail include sodium-lithium countertransport, intraerythrocytic sodium, sodium (or lithium)-potassium cotransport, lithium leak, sodium-potassium ATPase pump, sodium pump sites (ouabain binding), and circulating sodium pump inhibitor ('digoxin-like factor' in some studies). Countertransport, intraerythrocytic sodium and cotransport consistently show different values in hypertensives compared to normotensives and even in normotensives with a positive family history of hypertension when compared to controls without a positive family history. Thorough genetic studies have been carried out only for sodium-lithium countertransport and intraerythrocytic sodium. Both of these tests are highly heritable with a combination of both polygenic and major gene effects. Cotransport, leak, and pump sites also seem to be quite significantly heritable whereas the ATPase pump activity and the circulating pump inhibitor seem to be largely determined by nongenetic factors. Some of the most dramatic changes in these tests have been observed during pregnancy. Significant increases are seen in countertransport, cotransport, ouabain binding sites, and digoxin-like factor. Oral contraceptives also seem to affect at least cotransport. Plasma triglyceride level and body weight are some of the strongest correlates of countertransport, cotransport, and lithium leak. Cotransport increases with higher dietary sodium intake and decreases with the use of the diuretic medication. In the current developmental stage these tests have several significant limitations. In most population studies there is a considerable overlap of test values between persons with high and normal blood pressure. There are substantial variations in the methods used by different laboratories for the same tests. They are expensive, complex and usually must be done on fresh cells. There are conflicts between the results of several different reported studies that could be due to the way in which their subjects were selected, the effects of medications or other uncontrolled variables, or even due to the differences in laboratory methodologies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genetic and epidemiological studies on electrolyte transport systems in hypertension. 306 Feb 95

Intracellular concentration of sodium ([Na]i) and potassium ([K]i), and the ouabain sensitive sodium efflux rate constant (ERCos) in erythrocytes were determined in patients with primary aldosteronism, before and after the surgical removal of the adrenocortical adenoma and in comparison to those in healthy controls. Without treatment, [Na]i was higher and ERCos was lower in patients with primary aldosteronism than in controls (10.60 +/- 0.96 vs. 8.25 +/- 0.89 mmol/l cells, p less than 0.01; 0.156 +/- 0.040 vs. 0.255 +/- 0.047/hour, p less than 0.01, respectively). After the surgery, [Na]i was decreased to 7.70 +/- 0.64 mmol/l cells and ERCos was increased to 0.273 +/- 0.031/hour and these values were similar to those in controls. [K]i in primary aldosteronism was not affected by the surgery (from 96.79 +/- 2.03 to 98.8 +/- 3.84 mmol/l cells) and was not different from that in controls (99.11 +/- 3.42 mmol/l cells). In 2 patients, normalization of the serum potassium following an oral potassium chloride supplement caused only partial improvement in [Na]i and ERCos. These results suggest that an inhibition of sodium pump activity resulting in elevated [Na]i may play an important role in the pathogenesis of high blood pressure in patients with primary aldosteronism.
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PMID:Intracellular sodium and potassium concentrations in erythrocytes of patients with primary aldosteronism. 319 58


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