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

Cardiac hypertrophy which occurs during chronic arterial hypertension is one of the numerous examples of biological adaptation to environmental requirements. As such, it is obtained at random by trial and error, and adaptation represents the sum of various modifications in gene expression, including the shift in isomyosin or in iso-Na+,K(+)-ATPase, the decrease in beta 1-adrenergic or muscarinic receptors or in sarcoplasmic reticulum Ca(2+)-ATPase densities, and the unchanged density in calcium channels and current. Some of these changes are beneficial at the cellular level but are finally detrimental for the organism as a whole, such as slowing of maximum shortening velocity (Vmax). The prolonged calcium transient is likely to be a consequence of the various modifications of the membranes phenotype and provides a rational basis for arrhythmogenicity of the hypertrophied heart. There are also detrimental modifications, such as the increased collagen concentration and vascular hypertrophy, which may result from the accompanying changes in plasma content in several hormones or peptides.
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PMID:Biological adaptation and dysadaptation of the heart to chronic arterial hypertension: a review. 168 53

Enhanced Na+ and water reabsorption by proximal tubular epithelial cells plays an important role in the development of systemic hypertension associated with cyclosporine immunosuppression. Since such Na+ reabsorption is subserved by sodium-potassium adenosine triphosphatase (Na-K ATPase), the current study compared the acute effects of hydrocortisone (H), cyclosporine, and FK506 on cultured LLC-PK1 cell viability and on Na-K ATPase activity. Phospholipase-C (PL-C) activity was also investigated because of its possible regulatory effect on Na-K ATPase activity. Culture medium containing low (5 nM, 4.1 ng/ml) or high (10 nM) concentrations of FK506 plus cyclosporine at 415 microM (500 ng/ml) resulted in cell death, whereas cyclosporine concentrations of 83 microM plus 5 nM or 10 nM FK506, or isolated use of the two drugs at high dosages, did not affect cell viability. As compared with controls, cyclosporine increased Na-K ATPase activity, particularly with addition of H (P less than 0.01). In contrast, FK506 reduced the specific activity of both PL-cyclosporine and Na-K ATPase (P less than 0.001-0.01); addition of H to FK506 resulted in an even greater fall in both the enzyme activities (P less than 0.001). Na-K ATPase activity increased in cell homogenates briefly incubated with cyclosporine in the ATPase reaction mixture (P less than 0.05) while FK506 reduced such enzyme activity (P less than 0.05), suggesting a direct effect of these agents on pump activity. These data in LLC-PK1 cells pocessing proximal tubular epithelial cell characteristics indicate that the combined use of cyclosporine plus FK506 may be very deleterious to viability in such cells. The opposing effects of cyclosporine and FK506 on PL-cyclosporine and Na-K ATPase activities and the possible potentiating effect of H on such responses are speculated to affect Na+ and water homeostasis in a manner that may explain differences in systemic blood pressure due to these agents.
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PMID:Phospholipase-C and Na-K ATPase activation by cyclosporine and FK506 in LLC-PK1, cells. Possible implications in blood pressure regulation. 171 43

The effects of increased dietary calcium on the development of hypertension and vascular smooth muscle responses were studied in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Both hypertensive and normotensive animals were divided into two groups; the calcium content of the normal diet was 1.1% and that of the high calcium diet 3.1%. During the 12-week study, calcium supplementation significantly attenuated the increase in systolic blood pressure in the hypertensive rats but did not affect blood pressure in the normotensive rats. The contractile responses of endothelium-denuded mesenteric arterial rings to potassium chloride were similar in all study groups. The contractions to norepinephrine were not altered by the high calcium diet either, but smooth muscle sensitivity to this agonist was lower in the normotensive than in the hypertensive rats. Potassium relaxation was used to evaluate the activity of vascular smooth muscle Na+,K(+)-ATPase. The maximal rate of potassium relaxation was fastest in the normotensive groups but was also clearly faster in calcium-treated hypertensive rats when compared with hypertensive rats on a normal diet. Platelets were used as a cell model for the analysis of intracellular free calcium concentration, which was measured by the fluorescent indicator quin-2. Intracellular free calcium was significantly reduced in the hypertensive rats by calcium supplementation and was not affected in the normotensive rats. In conclusion, a reduction of intracellular free calcium concentration indicating improved calcium regulation and a concomitant alteration in vascular relaxation probably reflecting increased activity of smooth muscle Na+,K(+)-ATPase may contribute to the blood pressure-lowering effect of a high calcium diet.
Hypertension 1992 Jan
PMID:High calcium diet augments vascular potassium relaxation in hypertensive rats. 173 Apr 43

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

Causes of hypertension have been well scrutinized, whereas the secondary, disabling effects of high blood pressure are less well investigated. We have used a rat model of hypertension and developed a technique to study the secondary vascular smooth muscle component of the disorder. Banding patterns of myosin heavy chain isoforms from rat aortae were examined using denaturing electrophoresis, Western blotting, immunochemical identification, and degradation studies. Myofibrillar ATPase activities were also measured. Left ventricular hypertrophy and hypertension were induced in rats by aortic banding just proximal to the renal artery. Aortic banding increased the heart weight/body weight (mg/g) ratio from 2.8 to 3.8 and mean aortic weight by 53%. Two distinct myosin heavy chain isoforms, molecular masses of 204 and 200 kDa, were identified by 4% sodium dodecyl sulphate-polyacrylamide electrophoresis of crude aortic extracts from normal rats in a relative molar ratio of 1.54:1. The development of significant thickening of the aorta was marked by substantial increases in aortic wall smooth muscle content but was not associated with any changes in distribution of the isoforms. The band patterns obtained on gel electrophoresis were not the result of contamination by other proteins, as Western blotting studies with specific antibodies demonstrated that the isoforms were smooth muscle in origin and were not derived from nonmuscle myosin sources. Myofibrillar ATPase activity of aortic smooth muscle from hypertensive rats was increased. It is suggested that this increase may be the result of post-transcriptional alterations of one or more sarcomeric proteins involved in the regulation of smooth muscle contraction.
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PMID:Myosin heavy chain isoform distribution in normal and hypertrophied rat aortic smooth muscle. 182 1

The mechanisms by which the aged heart adapts to a superimposed pressure load such as hypertension have not been described. We therefore investigated biochemical and molecular genetic adaptations in the 24-month-old rat heart subjected to renovascular hypertension. Compared with 4-month-old rats, aging was associated with a 68% increase in left ventricular mass without any change in heart weight-to-body weight ratio, a 33% reduction in calcium-activated myosin ATPase activity, and a shift from a V1 to a V3 predominant myosin heavy chain (MHC) isoform distribution. A 46% reduction in alpha-MHC mRNA and a reciprocal increase in beta-MHC mRNA was seen. When hypertension was superimposed, there was a further 75% increase in ventricular mass, a 63% increase in heart weight-to-body weight ratio, and a 19% reduction in myosin ATPase. Myosin isozyme distribution was further shifted to V3, and the ratio of alpha-MHC to beta-MHC mRNA was reduced. In addition, with hypertension a significant (greater than 50%) reduction in the mRNA level of the cardiac sarcoplasmic reticular calcium-activated ATPase was seen. These data demonstrate that the aged myocardium is able to respond to a superimposed pressure load with a molecular genetic and protein synthetic pattern of hypertrophy analogous to that seen in younger animals.
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PMID:Effect of aging and hypertension on myosin biochemistry and gene expression in the rat heart. 183 8

An endogenous ouabain-like sodium pump inhibitor was demonstrated originally in serum or plasma of acutely extracellular fluid volume (ECFV) expanded animals and humans. Since then numerous studies have confirmed the presence of ouabain-like factor(s) (OLF) in blood, urine, cerebrospinal fluid, and various tissues including the heart and hypothalamus. Some of these OLFs represent well-known endogenous compounds, eg, free unsaturated fatty acids, which in vitro exhibit inhibition of transepithelial sodium transport, direct inhibition of the Na-K-ATPase enzyme, displacement of 3H-ouabain from its membrane receptor, and crossreaction with a digoxin antibody. Small molecular weight (MW) OLFs of yet unknown peptidic or nonpeptidic nature, which may be of hypothalamic origin, were also detected in various animal models of hypertension and in hypertensive patients. They may play a pathophysiological role especially in salt- and volume-dependent forms of hypertension. Our results show that OLFs increase basal and vasopressin-stimulated intracellular Ca2+ release in rat vascular smooth muscle cells in culture and in human platelets similar to the newly discovered endothelin. In addition, a natriuretic factor (natriuretic hormone) was detected by bioassay in plasma and urine, whose activity changes in parallel with sodium intake. We found that this natriuretic factor is associated with small peptides with a MW of less than 1,000. It is, however, unlikely that the two biological properties, ie, the ouabain-like and natriuretic activities, reside in a single compound. A number of circulating OLFs is certainly not identical with a humoral natriuretic factor. Nevertheless, there is increasing evidence for multiple interactions between OLF and the atrial natriuretic peptide (ANP).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endogenous natriuretic and ouabain-like factors. Their roles in body fluid volume and blood pressure regulation. 184 64

Thirty-seven subjects with low- and normal-renin hypertension (plasma renin activity less than 0.45 ng/L/sec on a 100 mmol Na diet) were studied on a 10 and 100 mmol sodium diet (100 mmol K and 25 mmol Ca) to examine the effect of varied sodium intake on plasma Na,K-ATPase inhibitory activity (NKAIA) (% inhibition). On the 10 mmol Na diet, plasma NKAIA correlated with mean arterial pressure (MAP) (r = 0.384, P = .019). On the 100 mmol Na diet, plasma NKAIA correlated with daily urinary sodium excretion (r = 0.384, P = .019). With the increase in sodium intake, the mean change in MAP was 0.5 +/- 7.8 mm Hg (range -12.7 to 16.3) and the mean change in plasma NKAIA was -4.2 +/- 11.2% inhibition (range -37.5 to 16). The change in MAP was correlated to the change in plasma NKAIA (r = 0.384, P = .019). Plasma NKAIA is related to mean arterial pressure or urinary sodium excretion depending on the dietary sodium intake, and is related to sodium-induced changes in MAP in low and normal renin hypertensive patients.
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PMID:Plasma sodium-potassium ATPase inhibition activity in low- and normal-renin hypertension. 184 65

Several investigators have demonstrated the antihypertensive properties of potassium in various models of hypertension. The present studies were conducted to determine whether central mechanisms contribute to these salutary effects of potassium. In Inactin-anaesthetized rats, intracerebroventricular administration of KCl solutions (0.375, 0.75 and 1.25 mumol/5 microliters) produced concentration-dependent reductions in arterial pressure and heart rate. These effects were significantly attenuated by prior central administration of ouabain, a selective inhibitor of the sodium pump. In a separate series of experiments, prior central administration of alpha 1- and alpha 2-antagonist phentolamine, or the dopamine receptor (DA1 and DA2) antagonist RS-sulpiride, was also effective in inhibiting the hypotensive and bradycardiac effects of intracerebroventricular administration of potassium. Thus, these data suggest that activation of Na+,K(+)-ATPase and central noradrenergic and dopaminergic mechanisms are involved in the central actions of potassium and these central mechanisms may contribute to the salutary effects of a potassium-rich diet in hypertensive subjects. The present studies demonstrate a potentially important relationship between Na+,K(+)-ATPase activity in the central nervous system and neural regulation of arterial blood pressure.
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PMID:Role of Na+,K(+)-ATPase in the centrally mediated hypotensive effects of potassium in anaesthetized rats. 184 33

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


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