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

Endogenous digitalis-like factor (endalin) was investigated by measuring the ability of rat and human plasma and urine to inhibit [3H]ouabain-specific binding, digoxin-antidigoxin antibodies interaction, and renal Na+, K+-ATPase activity. Endalin was detected in plasma (and urine) of one third of 112 patients with sustained and moderate hypertension (Na+ intake = 110 mmol/l). Endalin tended to be increased in the more pronounced hypertensives. No correlation with any other clinical and biological parameter could be detected. An activity to inhibit Na+, K+-ATPase was also detected in the rat after acute and chronic Na+ loading, in reduced renal mass-type hypertension and in SHRs as compared to WKY rats. Comparison of the plasma and urine inhibitory effects in the different tests revealed some chemical heterogeneity. However, a compound possessing the biochemical and pharmacological characteristics of digitaline was extracted from human urine. Chromatographic and spectral analysis of about 1,000 liters revealed a compound with apparent chemical homogeneity, molecular weight around 500, devoid of peptidic bound and of aliphatic structure.
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PMID:Chemical and clinical studies of endogenous digitalis-like factor in hypertension. 243 46

The possible role of endogenous sodium pump inhibitors was studied in salt-sensitive rats of Dahl strain which were influenced by high salt intake either in youth (from prepuberty) or only in adulthood. The aim of our study was to search for the relations between the age-dependent blood pressure response to high salt intake and the changes in volume or distribution of body fluids, red cell ion transport or Na+,K+-ATPase activity in various tissues of salt-sensitive (S/JR) and salt-resistant (R/JR) rats. Salt hypertension was especially pronounced in those S/JR rats which were maintained on a high-salt diet from prepuberty. This was accompanied by the moderate expansion of body fluids in young but not in adult hypertensive animals. Na+,K+-ATPase activity was suppressed in both kidney and heart of young S/JR rats with salt hypertension while this was not true in adult hypertensive animals. On the other hand, no inhibition of sodium pump was observed in brain microsomes and erythrocytes of severely hypertensive young S/JR rats. Moreover, no increased levels of endogenous sodium pump inhibitors were detected in plasma of salt hypertensive S/JR rats. Thus our study indicated the age-dependent suppression of sodium pump activity in some tissues of salt hypertensive Dahl rats but we failed to confirm increased levels of circulating sodium pump inhibitors in young salt hypertensive rats.
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PMID:Sodium pump activity in young and adult salt hypertensive Dahl rats. 243 46

Anatagonists to angiotensin, catecholamines, aldosterone, and vasopressin have long been used to help determine agonist roles in hypertension. We here call attention to a possible extension of this approach to detect, evaluate, and treat vascular sodium transport defects in hypertension. Two basic types of transport defects have been identified in the blood vessels of hypertensive animals, increased sodium permeability and decreased sodium pump activity. Intravenous injection of 6-iodo-amiloride, a sodium channel blocker and vasodilator, produces an immediate and sustained decrease in blood pressure in two genetic models of hypertension characterized by increased permeability of the vascular smooth muscle cell membrane to sodium (Okamoto spontaneously hypertensive rat, Dahl salt sensitive rat), whereas it produces only a transient fall in arterial pressure in two renal models of hypertension having normal sodium permeability in vascular smooth muscle cells (reduced renal mass-saline rat, one-kidney, one clip rat). Canrenone, a metabolic product of spironolactone which can compete with oubain for binding to Na+,K+-ATPase at the digitalis receptor site, decreases blood pressure in a low renin, volume expanded model of hypertension which has been shown to have depressed sodium pump activity in arteries and increased sodium pump inhibitor in plasma (reduced renal mass-saline rat) but has no effect on blood pressure in a genetic model of hypertension which has been shown to have increased sodium pump activity secondary to increased sodium permeability (spontaneously hypertensive rat). Thus, a sodium channel blocker and a competitor to ouabain binding can detect and determine the functional significance of sodium transport defects in the blood vessels of intact hypertensive animals. Studies in red and white blood cells suggest that similar defects may exist in the blood vessels of hypertensive humans. Thus, this approach, probing for vascular transport defects in the intact animal, may ultimately also be useful in the clinical setting.
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PMID:Pharmacologic agents for the in vivo detection of vascular sodium transport defects in hypertension. 244 62

The effect of canrenone, an antialdosterone and partial ouabain-agonist drug, was studied in rats that developed volume expansion and hypertension after renal mass reduction and excess Na+ intake (RRM-salt). The RRM-salt was characterized by: (1) increased endogenous "digitalis-like" compounds in plasma [cross reactivity with digoxin-antibodies (57.5 +/- 5.0 vs. 42.1 +/- 3.8 pg/ml, p less than 0.02); inhibition of kidney Na+, K+-ATPase activity (135 +/- 5 vs. 154 +/- 5 mumol/mg/h, p less than 0.01); and inhibition of Na+ extrusion from normal erythrocytes (5.96 +/- 0.40 vs. 7.68 +/- 0.34 mmol/L cells/h, p less than 0.01)]; (2) reduced Na+, K+-pump activity (7.34 +/- 0.29 vs. 10.88 +/- 0.41 mmol/L cells/h, p less than 0.001) and increased Na+ content (4.66 +/- .08 vs. 4.16 +/- 0.11 mmol/L cells, p less than 0.01) in erythrocytes; and (3) low plasma renin activity (2.1 +/- 0.9 vs. 12.6 +/- 1.6 ng/ml/h). Ninety minutes after the administration to RRM-salt of a single oral dose of 60 mg/kg of canrenone, the systolic blood pressure decreased by 36 +/- 4 mm Hg (mean +/- SEM). Chronic canrenone administration (60 mg/kg/day) resulted in a marked antihypertensive effect associated to a correction of volume expansion, a decrease in endogenous "digitalis-like" compounds, and a partial recovery of Na+, K+-pump activity and Na+ content in erythrocytes. Our results suggest that the antihypertensive effect in RRM-salt rats results, at least in part, from antagonism with endogenous "digitalis-like" compounds.
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PMID:Antihypertensive effect of canrenone in a model where endogenous ouabain-like factors are present. 245 Feb 60

In normotensive humans with a positive family history of essential hypertension (FHH), blood pressure (BP) is often dysregulated. Resting BP already tends to be slightly higher than in age-matched control groups with negative FHH; BP responses to high sodium intake and perhaps to psychological and/or physical stress may also be exaggerated. Considering BP regulating factors, total exchangeable body sodium, whole blood volume, and their responses to low or high sodium intakes are normal in normotensive subjects with positive FHH; this does not exclude an existing although fully compensated regulatory disturbance. The response of plasma immunoreactive atrial natriuretic peptide levels to a high sodium intake seems to be impaired. On the other hand, a tendency for high ouabain-like Na+/K+-ATPase activity was reported in some normotensive subjects with positive FHH; data on central blood volume are lacking. Basal plasma renin, angiotensin II (AngII), and aldosterone levels, the reactivity of BP to acute increases in circulating AngII, and the responses of these variables to changes in sodium intake did not differe significantly between normotensive groups with a negative or positive FHH; this does not exclude a tendency for low renin-angiotensin activity in certain hypertension-prone families. The responsiveness of plasma aldosterone to acute rises in circulating AngII appeared to be largely unaltered when normotensive subjects with positive FHH were on moderate or high sodium intakes, but aldosterone responses may be blunted on a low sodium diet. Although a familial occurrence of subtle disturbances in AngII-dependent control of aldosterone and renal hemodynamics appears possible, BP regulation by the renin-angiotensin system is probably often intact at the stage of prehypertension. The finding of unaltered basal peripheral venous plasma norepinephrine (NE) and epinephrine levels and NE responses to changes in sodium intake, posture, or physical exercise in normotensive subjects with positive FHH has so far provided no evidence for enhanced sympathetic activity; nevertheless, direct analysis of regional nerve activity or NE release will be required to resolve this question. Regardless of the level of sympathetic activity, an exaggerated pressor responsiveness to NE occurs as a common disturbance in normotensive subjects with a positive FHH.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dysregulation of blood pressure in normotensive offspring of hypertensive parents. 246 99

Alterations in cellular calcium metabolism are presumed to be the basis of the vasoconstrictive process that sustains elevations in arterial pressure. Altered membrane sodium transport can effect changes in intracellular free calcium concentration through changes in transmembrane sodium gradients and membrane depolarization. Thus, changes in membrane sodium transport could produce calcium accumulation in vascular smooth muscle, resulting in vasoconstriction and arterial hypertension. Multiple sodium transport abnormalities exist in tissues of genetically hypertensive rats, and blood cells of human essential hypertensives. Na+-K+ cotransport and Na+-Li+ countertransport abnormalities appear to be primary membrane defects, but a direct physiologic link of these to vasoconstriction remains to be established. Evidence for circulating Na,K-ATPase inhibitors in hypertension is now widely reported, and Na,K-ATPase inhibition provides a rationale for vasoconstriction through altered calcium and/or neurotransmitter metabolism. Na,K-ATPase inhibition in hypertensive disease appears to arise not as a primary abnormality in membrane transport, nor as a phenomenon secondary to hypertension per se, but as a physiological response to compensate for excess extracellular fluid volume accumulation.
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PMID:Circulating inhibitors of sodium transport at the prehypertensive stage of essential hypertension. 246 9

The manifestations of cardiac involvement in hypertension include: (1) the development of hypertensive heart disease characterized by left ventricular hypertrophy (LVH), and (2) the consequences of coronary atherosclerosis, as angina pectoris, myocardial infarction, and sudden cardiac death. Whereas the former is directly related to increased blood pressure, the latter are sequelae of atherosclerosis per se, and hypertension acts only as a risk factor in this regard. This can partially explain why antihypertensive treatment is effective in diminishing the incidence of congestive heart failure, which is the final consequence of LVH, but is not very effective in preventing coronary complications. It is generally accepted about LVH that increased arterial pressure is the major stimulus to cardiac hypertrophy in hypertension; however, there are a lot of both quantitative and qualitative events suggesting that other factors beside blood pressure levels can modulate the development of LVH, in particular neurohumoral influences. From a morphological point of view, hypertrophy of the cardiac muscle is defined as an increase in the size of existing myocardial fibers. In most experimental models, myocardial hypertrophy is associated with myosin isoenzymatic changes, consisting in a shift from the faster migrating isoenzyme V1 to V3, a form that migrates more slowly. However these changes do not occur in all animal species and particularly in humans. In the hypertrophied human ventricle, a decreased ATPase activity of myofibrils was observed, probably related to changes in myosin light chains. Presently the changes in ATPase activity and in ventricular contractility do not still have a clear molecular basis in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heart and hypertension. 252 4

The effect of an acute saline load on the sodium pump was determined from measurements of intracellular sodium and potassium, ouabain-inhibitable sodium efflux, and the number of sodium-potassium adenosine triphosphatase (Na,K-ATPase) sites per cell (using 3H-ouabain binding) of erythrocytes from 22 hypertensive and 21 normotensive subjects before and after a 2-1 infusion of 0.9% saline over a 4-hour period. Before the infusion, ouabain-inhibitable sodium efflux was the only measured parameter that was significantly (p less than 0.025) different between hypertensive (1.65 +/- 0.21 mmol/l red blood cell [RBC]/hr) and normotensive (1.46 +/- 0.25 mmol/l RBC/hr) subjects. After the saline infusion, there was a significant (p less than 0.001) decrease in the ouabain-sensitive sodium efflux of the hypertensive (1.55 +/- 0.22 mmol/l RBC/hr) but not of the normotensive (1.48 +/- 0.43 mmol/l RBC/hr) subjects. Although the changes in intracellular sodium of the normotensive and hypertensive subjects caused by the saline infusion were not significant, the fact that the change was in opposite directions in the two groups yielded a significant (p less than 0.02) differential response. After the saline infusion there was a significant increase in intracellular potassium (p less than 0.001, paired t test) and in the 3H-ouabain-binding affinity constant (p less than 0.001, paired t test) for both hypertensive and normotensive subjects. A second-order rate constant, which is an estimate of the apparent affinity constant of the sodium pump, was calculated from the ouabain-inhibitable sodium efflux, the intracellular sodium, and the number of Na,K-ATPase sites per cell.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1989 Jan
PMID:Acute sodium loading alters sodium pump in Caucasian hypertensive subjects. 253 1

Based on a review of literature in various fields of research related to hypertension, we develop a new working hypothesis on the pathophysiology of genetically determined increases in blood pressure. According to our hypothesis, the primary defect is located in the kidneys. Renal alpha-adrenergic receptor density is increased in the early stages of the disease, before increases in blood pressure occur. Most renal alpha-adrenergic receptors are located in the proximal tubules and enhance Na+ reabsorption. A genetically determined increase of alpha 1- or alpha 2- or of both alpha-adrenergic receptor subtypes would impair Na+ excretion and, together with increased Na+ intake, would lead to positive Na+ balance. Subsequently, various mechanisms would be activated to restore a neutral Na+ balance, including the secretion of a natriuretic factor that inhibits Na+/K+-ATPase. Inhibition of Na+/K+-ATPase in extrarenal tissues would increase the intracellular concentration of Na+ and, via Na+/Ca2+ exchange, of Ca2+. Elevated intracellular Ca2+ would enhance vascular smooth muscle contractility and neuronal transmitter release, thereby leading to vasoconstriction and to increases in blood pressure. We thus hypothesize that hypertension is a homeostatic response designed to protect blood volume from a genetically determined renal alpha-adrenergic receptor-mediated increase in Na+ retention.
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PMID:Renal alpha-adrenergic receptor alterations: a cause of essential hypertension? 253 29

The purpose of the present study was to examine the role of Na+,K+-ATPase activity in vascular adrenergic transmission of hypertension. In isolated perfused mesenteric vasculatures of spontaneously hypertensive rats (SHR, Okamoto and Aoki strain, seven- to ten-weeks-old) and age-matched Wistar Kyoto rats (WKY), the effects of ouabain, a potent Na+,K+-ATPase inhibitor, or partially purified plasma obtained from salt-induced hypertension on pressor responses and norepinephrine overflow were investigated. Pressor responses and norepinephrine overflow during electrical nerve stimulation were significantly greater in SHR than in WKY. Ouabain increased the stimulation-evoked pressor responses and norepinephrine overflow. This facilitation was more prominent in SHR than in WKY. Partially purified plasma obtained from reduced renal mass-salt hypertensive rats, which had a crossimmunoreactivity with digoxin, also increased the pressor responses and norepinephrine overflow during electrical nerve stimulation, and the effects were greater in SHR than in WKY. These results suggest that Na+,K+-ATPase on vascular adrenergic neurons has an important role in the regulation of neurotransmitter release, and that its activity might be enhanced in SHR.
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PMID:Facilitatory effects of ouabain and digitalis-like substance on adrenergic transmission in hypertension. 254 98


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