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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abundant experimental data suggest that an endogenous digitalislike factor is responsible for some essential hypertension. Some forms of hypertension have also been associated with increased levels of catecholamines. We therefore designed experiments to investigate the role of digitalislike factors in the regulation of norepinephrine turnover in the neurovascular junction. We chose bufalin, an amphibian-derived compound that shares many of the physiological properties postulated as characteristic of digitalislike compounds, as a model of the mammalian compound. In vitro experiments in canine saphenous veins showed that, in addition to inhibiting norepinephrine uptake, bufalin increased norepinephrine overflow by an amount larger than could be explained solely by uptake inhibition. The effect of bufalin on norepinephrine overflow is inhibited by tetrodotoxin, which suggests a dependence of this response on Na+ influx through the neuronal membranes. We propose that Na+,K(+)-ATPase inhibition resulting in neuronal depolarization is responsible for the augmented norepinephrine turnover caused by bufalin and that these indirect effects of norepinephrine on the cardiovascular system may play a role in the etiology of hypertension.
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PMID:Effects of bufalin on norepinephrine turnover in canine saphenous vein. 165 48

In the present study, we have examined the effects of ouabain on membrane fluidity of erythrocytes by use of an electron spin resonance (ESR) and spin-labeling method, and elucidated a possible role of Na+, K(+)-ATPase in the regulation of membrane fluidity in hypertension. Erythrocytes obtained from patients with essential hypertension were examined compared with those from age-matched normotensive subjects, and the ESR spectra for 5-nitroxy stearate incorporated into erythrocyte membranes were studied. The values of outer hyperfine splitting and order parameter (S) of the ESR spectra were significantly higher in patients with essential hypertension than in normotensive subjects. This finding shows that the membrane fluidity of erythrocytes might be lower in essential hypertension. Ouabain loading to erythrocytes decreased the membrane fluidity (S value was increased). The alternative degree was significantly greater in essential hypertension than in normotensive subjects. These results demonstrate that the membrane fluidity of erythrocytes might be highly dependent on the Na+, K(+)-ATPase activity in essential hypertension, which would suggest an abnormality in Na(+)-related cellular functions in hypertension.
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PMID:Effects of ouabain on membrane fluidity of erythrocytes in essential hypertension. An electron spin resonance study. 165 45

Essential hypertension is primarily hereditary. The property inherited is present in all cells but because of adaptation and differentiation it is particularly prominent in systemic vascular smooth muscle. This inherited property is manifested functionally as increased reactivity to vasoactive substances, such as (-)noradrenaline and angiotensin II. This abnormal function is present before the onset of hypertension. Vascular hypertrophy and hyperplasia are not only caused by hyperactivity of the smooth muscle and by the hypertension itself but are also trophic effect of the agonists, especially noradrenaline. The only two proteins in vascular smooth muscle which can produce both contractile and trophic effects are the guanosine triphosphate binding protein (Gs) and phospholipase C. Phospholipase C has already been demonstrated to be abnormally active in response to agonists in the spontaneously hypertensive rat and in human essential hypertension. The Gs protein is less likely to be critically abnormal since it is active in the vascular smooth muscle relaxation cascade as well as in contraction. None of the other proteins involved in vascular smooth muscle contraction or relaxation affect both contractile reactivity and cellular growth. There are many secondary effects dependent upon the phospholipase C abnormality such as calcium (Ca2+) cellular content, Ca2+ Mg2+ ATPase pump effects and possibly Ca2+ Na+ exchange. There are also many secondary effects impinging on the phospholipase C abnormality including changes in noradrenaline and angiotensin II metabolism. Present antihypertensive therapy is directed largely at secondary factors dependent upon or influencing the primary phospholipase C cascade. The path is now open for a more direct and basic diagnostic and therapeutic attack.
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PMID:The aetiology of essential hypertension. 177 Apr 74

To investigate the mechanism whereby blood pressure rises with NaCl loading in salt-sensitive essential hypertension, salt-sensitivity index was determined along with sodium and lithium clearances, plasma Na+,K(+)-ATPase inhibitor and intra-erythrocyte sodium and potassium concentrations. Salt-sensitivity index was defined as the percentage of change in mean blood pressure when NaCl intake was changed from low (34 mmol/day) to high (342 mmol/day). Salt-sensitivity index was inversely correlated with fractional excretion of lithium both on the low and high NaCl diets (r = -0.721, P less than 0.01 and r = -0.591, P less than 0.02, respectively; n = 16), but not with fractional excretion of sodium. The change of plasma Na+,K(+)-ATPase inhibition with NaCl loading had a direct correlation with salt-sensitivity index (r = 0.704, P less than 0.01; n = 16). Either intra-erythrocyte sodium and potassium concentrations or the ratio of these two values did not change significantly with an increase of dietary NaCl intake. These results suggest that an enhancement of proximal tubular sodium reabsorption stimulates secretion of plasma Na+,K(+)-ATPase inhibitor which may be involved in a rise in blood pressure with sodium loading. They also suggest that lithium clearance is a determinant which can predict salt sensitivity without actual NaCl loading.
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PMID:Renal sodium handling and sodium transport inhibitor in salt-sensitive essential hypertension. 184 59

Several studies have recently demonstrated that the platelets of subjects affected by essential hypertension have, in their basal state, an elevated cellular calcium content. Such data appear particularly interesting with regard to gestational hypertension (GH). Supposing that the intracellular calcium may be involved in the regulation of blood pressure we have studied the cytosolic calcium concentration, Na+/K(+)-ATPase activity, Ca(2+)-ATPase activity, fluidity, and the cholesterol/phospholipid (C/P) molar ratio of the plasma membranes in platelets from 20 normotensive pregnant women and 20 women affected by mild gestational hypertension without pharmacological treatment, near term. We observed an increased Ca(2+)-ATPase activity and a decreased Na(+)K(+)-ATPase activity in GH compared to the controls, accompanied by an increased Ca2+ intraplatelet concentration in the same patients. The fluidity and the C/P molar ratio were also increased. Our study gives indirect support to the hypothesis, supposing a reduced Na+/K(+)-ATPase activity which might cause increased intracellular Na+ content and decreased Ca2+ efflux through the Na+/Ca2+ exchange. However, out data can not rule out the other hypotheses explaining the increased cellular Ca2+ content. The present data indicate that GH is accompanied by a membrane structural abnormality that alters its physical state and modifies the membrane-related cellular functions.
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PMID:Modifications induced by gestational hypertension on platelet calcium transport. 185 87

Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver--key sites for cell and water homeostasis and lipoprotein regulation, respectively--may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. 186 24

This review first summarizes evidence from animals and humans for and against a role for dietary sodium in the genesis and treatment of hypertension. The evidence for its role is strongest in those subjects with impaired ability to excrete sodium because of organic renal disease or mineralocorticoid excess. Here, restriction of dietary sodium promptly lowers pressure. Its role in the genesis of essential hypertension is more controversial. Nevertheless, it appears that some patients with mild to moderate essential hypertension respond to moderate sodium restriction with a modest fall in pressure. This restriction also seems to reduce the amount of antihypertensive medication needed to keep pressure under control. Next, the mechanism of the pressure response to dietary sodium chloride is considered, with emphasis on potassium depletion and increased plasma levels of prohypertensive sodium pump inhibitor and antihypertensive atrial natriuretic peptide. The evidence for a primary role for dietary potassium in the genesis of hypertension then is summarized; certain subsets of subjects with a high incidence of hypertension also have a lower potassium intake. Some investigators have found that dietary potassium supplementation lowers pressure in established hypertension. This may result from natriuresis and from vasodilation subsequent to stimulation of Na+,K(+)-ATPase in vascular smooth muscle and adrenergic nerve terminals. After the role of dietary calcium is discussed, practical aspects of dietary sodium restriction and dietary potassium supplementation in the therapy for established hypertension are considered. The review concludes with comments on their possible roles in the prevention of hypertension.
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PMID:Roles of sodium, potassium, calcium, and natriuretic factors in hypertension. 193 82

A study was made of transmembranous ionic transport enzymes (Na(+)-K(+)-, Mg2(+)- and Ca2(+)-ATPases) in 95 patients with essential hypertension (EH) and 39 healthy persons. The activity of Na(+)-K(+)-ATPase was decreased for the most part at the early stages of EH. Measurements of the content of natriuretic hormone in the plasma did not reveal any significant differences between EH patients and healthy persons. However, the daily excretion of natriuretic hormone was significantly increased at the early stages of EH, which correlated with the changes in the activity of Na(+)-K(+)-ATPase in red blood cell membranes. This may lead to the derangement of homeostasis of intracellular electrolytes, attesting to an important role played by these factors in the pathogenesis of EH. As EH progressed, the cholesterol/phospholipid ratio increased which may also influence the activity of Na(+)-K(+)-ATPase. After enlargement of the intravascular liquid volume (drinking load 22 ml/kg) the EH patients manifested the loss of an adequate reaction of Na(+)-K(+)-ATPase towards elevated production of natriuretic hormone.
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PMID:[Effect of natriuretic hormone and changes in the lipid spectrum of erythrocyte membranes on the activity of enzymes of transmembrane ion transport in patients with essential hypertension]. 196 48

The biological characteristics of a line of stress-sensitive hypertensive (SSH) rats genetically selected from Wistar rats are described, in particular the dynamics of arterial blood pressure and the biochemical properties of the Na(+)-K+ ATPase present in the outer renal medulla. Changes in the specific activity of this enzyme are discussed in terms of the lipid composition of the membrane bilayer and the amount of endogenous ouabain-like compounds present in the blood of the animals under study. Rats of both strains, Wistar and SSH, were studied under conditions of rest and stress (8 day regime of daily 30 min immobilization). The production in vivo of adrenal mineralocorticoids and glucocorticoids is estimated and several biochemical features of the pathogenesis of essential hypertension are discussed.
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PMID:The biochemical characteristics of stress-sensitive hypertensive rats. 196 83

The causes of elevated intra-erythrocyte calcium in the offspring of essential hypertensive patients are unknown. Fourteen children with and without a family history of essential hypertension were chosen to compare erythrocyte membrane Ca2(+)-Mg2(+)-ATPase activity (Rbc-M Ca2(+)-Mg2(+)-ATPase activity) measured by biochemical methods. We found that Rbc-M Ca2(+)-Mg2(+)-ATPase activity was lower in children with family history of hypertension compared with children with no family history (2.16 +/- 1.10 vs 3.36 +/- 1.19 microM Pi/mg protein/hour P less than 0.01). These results suggest that the reduced Rbc-M Ca2(+)-Mg2(+)-ATPase activity may be one of the mechanisms causing the high erythrocyte calcium levels in the offspring of essential hypertensive patients.
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PMID:Comparison of erythrocyte membrane Ca2(+)-Mg2(+)-ATPase activity in children with and without family history of essential hypertension. 214 Jan 35


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