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

Alterations in endothelium-dependent, sodium pump-mediated, and calcium-dependent responses of vascular smooth muscle were investigated in 5-7-, 24-26-, and 50-52-week-old male Sprague-Dawley rats. Age-dependent changes in systolic blood pressure were also determined. Although systolic blood pressure increased significantly with age, rats in all 3 age groups were considered normotensive. Initial studies on the passive force-response characteristics of strips of aortic and femoral arterial smooth muscle revealed that the level of passive force required for maximum active tension generation increased with increasing age. Subsequent studies were carried out using optimum passive force requirements. Endothelium-dependent relaxations of aortic smooth muscle induced by acetylcholine and the calcium ionophore A23187 decreased significantly with increasing age. An age-dependent decrease in the contractile response of aortic smooth muscle to ouabain and potassium-free physiological salt solution (PSS) was observed. Potassium relaxation of femoral smooth muscle following contraction to norepinephrine (NE) in a potassium-free PSS was also significantly attenuated with increasing age. No age-related alterations in calcium sensitivity (in the presence of 10(-7) M NE) or calcium relaxation (membrane stabilization) of femoral arterial smooth muscle was seen. These results show that endothelium-dependent and sodium pump-mediated responses are reduced in vascular smooth muscle of the rat with increasing age. However, no changes in calcium-dependent responses are apparent. These observations are discussed in relation to the vascular changes observed in hypertension.
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PMID:Effect of age on blood pressure and membrane-dependent vascular responses in the rat. 244 2

Passive and active carrier-mediated transport of sodium across vascular muscle membranes has been suggested to be more important in the increased total peripheral resistance found in genetic hypertension. Using manipulations of ion gradients and recordings of ion currents, membrane potentials, and tension, I have found evidence for calcium regulation as the central pathophysiological mechanism in spontaneously hypertensive rats. Increased sodium pump activity, which may be a partial compensation for the increased sodium influx in hypertension, may thus be secondary to altered calcium channel regulation in hypertension. The calcium channel, and the membrane potentials governing it, seem to be the most immediately important membrane mechanisms for hypertension research.
Hypertension 1987 Nov
PMID:Vascular muscle membrane cation mechanisms and total peripheral resistance. 244 79

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 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

To elucidate the effects of magnesium on high blood pressure, a 4-week study of oral magnesium supplementation (MgO 1 g/day) was conducted in 21 outpatients with uncomplicated essential hypertension. During the study, blood pressure and intraerythrocyte sodium concentration decreased significantly, and the erythrocyte ouabain-sensitive 22Na efflux rate constant (Kos) and intraerythrocyte magnesium concentration both increased. Serum triglyceride and free fatty acid concentrations were reduced. Furthermore, the elevation in Kos significantly and positively correlated with both the increase in intraerythrocyte magnesium concentration and the decrease in mean blood pressure. There was a significant inverse correlation between the prestudy Kos and the decrease in mean blood pressure. In addition, when patients were divided according to their overall decrease in mean blood pressure, the prestudy intraerythrocyte sodium concentration was significantly higher in patients with a mean blood pressure decrease of more than 7 mm Hg than that of patients whose mean blood pressure decrease was less than 7 mm Hg. These results suggest that oral magnesium supplementation may lower blood pressure through the activation of a cell membrane sodium pump and may reduce serum lipid concentration. It also suggests that the lower the prestudy Kos or the higher the prestudy intraerythrocyte sodium concentration, the more effective the oral magnesium treatment is in lowering blood pressure. Therefore, we concluded that appropriate oral magnesium intake might be effective as a nonpharmacological treatment for essential hypertension.
Hypertension 1989 Mar
PMID:Oral magnesium supplementation in patients with essential hypertension. 253 96

Erythrocyte sodium and sodium fluxes in plasma and in physiological buffer solution were studied in normotensive and hypertensive uraemic patients and normal subjects. Erythrocyte sodium was reduced in the uraemic patients due primarily to low sodium influx, further supported by low passive membrane permeability. These differences were much more marked in normotensive patients. There was no evidence for sodium pump inhibition in the erythrocytes. The low erythrocyte sodium influx in the uraemic patients appeared to be due to a plasma factor which could be reversed in young cells but not in old. However, erythrocyte sodium flux in both plasma and physiological buffer was lower in normotensive than in hypertensive uraemic patients. Therefore, a membrane change to compensate for the effects of the plasma factor on sodium influx may be related to the development of hypertension in the uraemic patients.
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PMID:Erythrocyte sodium and sodium flux in relation to hypertension in chronic renal failure. 253 80

An endogenous sodium pump inhibitor has been purified from human plasma. The purification scheme involved large scale dialysis, extraction of lyophilized dialysate by methanol followed by preparative and semipreparative scale reverse-phase high-performance chromatography. A single peak of biologically active material was obtained enriched by a factor of greater than 10 billion. This material showed high chromatographic polarity, was inactivated by charring, strong acid, or alkali, and was resistant to short-term boiling. The purified material had a molecular weight between 300 and 900 g/mol and was insensitive to type I esterase and a variety of proteolytic enzymes. The purified factor inhibited the ouabain-sensitive uptake of 86Rb by human erythrocytes, binding of [3H]ouabain, and activity of dog kidney Na,K-adenosine triphosphatase (ATPase) with high affinity (less than 0.3 nM) in a time- and dose-dependent manner. Maximally effective concentrations of the digitalislike factor showed no effect on either human red blood cell Mg- or Ca-ATPase, rabbit muscle sarcoplasmic reticulum Ca-ATPase, or guinea pig stomach H,K-ATPase. The purified material is a highly potent selective inhibitor of the ion transport, receptor, and hydrolytic functions of the sodium pump. The characteristic properties of this substance suggest it may be a mammalian endogenous digitalis and may be similar to the sodium transport inhibitor detected in the plasma of volume-sensitive forms of experimental and human hypertension.
Hypertension 1989 Jun
PMID:Isolation and characterization of a sodium pump inhibitor from human plasma. 254 19

Abnormalities in erythrocyte Li-Na countertransport have been reported in hypertensive subjects, and the available evidence favors familial aggregation and striking heritability of this marker. It is uncertain, however, whether the abnormalities are associated with hypertension per se or whether they may be concentrated in a particular subset of hypertensive subjects. In the present study, maximal rates of Li-Na countertransport were measured in red blood cells of 82 white subjects, including 37 normotensive subjects and 45 normal- or high-renin hypertensive subjects previously classified as non-modulators (n = 21) or modulators (n = 24). Mean countertransport activity was significantly higher in non-modulators compared with normally modulating hypertensive or normotensive subjects (0.475 +/- 0.044 vs. 0.309 +/- 0.028 or 0.249 +/- 0.012 mmol/l cell x hr, respectively, p less than 0.001). Modulators did not differ significantly from normotensive subjects with regard to mean countertransport activity. Red blood cell sodium pump and Na-K-Cl cotransport were not significantly different in modulating and non-modulating hypertensive subjects. These relations remained unchanged after adjusting for age, body weight, and plasma cholesterol levels by analysis of covariance. A countertransport value exceeding 0.50 mmol/l cell x hr occurred in 40% of the non-modulators but in only one of the other subjects. In contrast , while one half of the modulators and normotensive subjects had a countertransport value less than 0.235 mmol/l cell x hr, none of the non-modulators did. Thus, elevated countertransport appears to aggregate in the non-modulating subset of essential hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1989 Jun
PMID:Red blood cell lithium-sodium countertransport in non-modulating essential hypertension. 254 20

We were able to purify two distinct sodium pump inhibitors to homogeneity from human urine based on [3H]ouabain-displacing activity from intact human erythrocytes. The polar and less polar compounds were eluted off the C18 reverse-phase column with 18% and 31% acetonitrile, respectively. The polar compound cross-reacted very weakly with specific antidigoxin antibody and lacked a characteristic ultraviolet absorption peak between 190 and 300 nm. The less polar compound showed a prominent digoxinlike immunoreactivity and had an ultraviolet spectrum similar to that of digoxin. We examined the effects of these compounds on cytosolic free calcium concentration in cultured rat vascular smooth muscle cells (A10 cells) using the fluorescent calcium chelator fura-2. Only the polar ouabain-displacing compound caused a significant increase, from 108 +/- 7 to 162 +/- 8 nM (n = 6, p less than 0.01), in cytosolic free calcium concentration in A10 cells. The rise in cytosolic free calcium concentration induced by the polar ouabain-displacing compound tended to be slower in onset and more sustained than that induced by arginine vasopressin. In contrast, ouabain and bufalin had no appreciable effects on cytosolic free calcium concentration in A10 cells. These results suggest that the polar ouabain-displacing compound we isolated from human urine may possess a vasoactive property and may play an important role in the modulation of vascular tone.
Hypertension 1989 Jun
PMID:Urinary sodium pump inhibitor raises cytosolic free calcium concentration in rat aorta. 254 27

To study the circulating humoral factor modifying transmembrane sodium transport, plasma was obtained from 12 patients with essential hypertension (EH) fed a high sodium diet (NaCl 15 to 17 g/d) for seven days and thereafter a low sodium diet (NaCl 2 to 3 g/d) for seven days. Ouabain-sensitive 86Rb+ influx into the red blood cells (RBC) obtained from a healthy subject, and incubated with the plasma obtained during the high sodium diet was significantly lower than that incubated with the plasma obtained during the low sodium diet (3.74 +/- 0.26 v 3.97 +/- 0.30 nmol/10(8) cells, P less than .05). The changes in mean blood pressure from the high to low sodium diet showed a significant positive correlation with the changes in the ouabain-sensitive Rb influx into RBC in the plasma from the high to low sodium diet. These results suggest that a humoral factor modifying the sodium pump might be altered by sodium balance in EH, especially in salt-sensitive hypertension.
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PMID:Effect of dietary sodium on the Na-K ATPase inhibitor in patients with essential hypertension. 254


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