Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenous digitalislike compound (or compounds) has been described as involved in some diseases. Questions remain concerning its chemical nature, origin, and biological properties. The methods of measuring the compound are based on biological properties of digitalis, mainly Na+, K+-adenosine triphosphatase (ATPase) inhibition and related properties. Chemically, digitalislike compound has been described as a peptide, as fatty acids, and as a steroid. Its origin could be the brain, particularly the hypothalamus and pituitary gland. The adrenal glands were also proposed as its origin. The reported biological properties of digitalislike compound are mainly dependent on Na+, K+-ATPase inhibition. No definitive conclusions can be drawn from the available data.
Hypertension 1987 Nov
PMID:Endogenous digitalislike compounds. A tentative update of chemical and biological studies. 282 69

Increased levels of a humoral inhibitor of active sodium transport have been associated with the response to acute and chronic hypervolemia and various forms of experimental as well as human essential hypertension. In this report, we describe the purification of inhibitors of Na+, K+-adenosine triphosphatase (ATPase) from the plasma of volume-expanded individuals. Of the two amphipathic materials obtained, only one of the factors when present in high concentrations showed the slow time-dependent component of inactivation similar to that of the cardiac glycosides. Inhibition was reduced in the presence of plasma proteins and was freely reversible. Both factors inhibited potassium-dependent p-nitrophenylphosphatase activity and specific [3H]ouabain binding in a manner similar to the cardiac glycosides. In contrast to ouabain and vanadate, however, high concentrations of potassium or norepinephrine, respectively, did not affect the magnitude or kinetic characteristics of inhibition. Structural analysis by mass spectroscopy showed a mass of 444 for factor 1, whereas factor 2 was conclusively identified as lysophosphatidylcholine-gamma-palmitoyl. These factors probably inhibit Na+, K+-ATPase by a nonspecific mechanism involving reversible perturbation of lipid-enzyme interactions required for normal catalytic activity. The significance of these factors as modulators of sodium transport may be limited to pathological states associated with abnormalities in plasma protein binding or lipid metabolism. They do not appear to be directly related to the humorally mediated disturbance of cellular sodium transport in hypertension.
Hypertension 1987 Nov
PMID:Purification and characterization of digitalislike factors from human plasma. 282 70

The possibility that endogenous inhibitors of the sodium pump exist and bind to the cardiac glycoside binding site on Na+,K+-adenosine triphosphatase (ATPase) has been a source of much controversy. Although numerous hormones and inorganic ions that modulate Na+,K+-ATPase activity have been described, most of these affect the sodium pump indirectly by varying the intracellular sodium concentration or by increasing the number of enzyme units. None of these endogenous compounds has been shown conclusively to modulate sodium pump activity by binding to the cardiac glycoside binding site on Na+,K+-ATPase. However, the near-universal presence of three high-affinity binding sites on the alpha-subunit of the enzyme has engendered much speculation that endogenous ligands for these receptors must exist. In addition, none of the hormones known to indirectly affect sodium pump activity in vivo has been shown to modulate Na+,K+-ATPase activity in response to extracellular volume expansion or to play a role in the pathogenesis of hypertension or chronic renal failure, conditions in which a circulating inhibitor of Na+,K+-ATPase has been implicated. This report presents a condensed history of the search for endogenous inhibitors of Na+,K+-ATPase and describes recent advances in the field. Despite progress in identifying and characterizing compounds that could affect Na+,K+-ATPase activity in vivo, definitive proof for the existence of endogenous ligands for the cardiac glycoside binding site remains elusive.
Hypertension 1987 Nov
PMID:Endogenous cardiac glycosidelike compounds. 282 72

A 6.5-kilobase fragment of genomic DNA from mutant mouse cells under ouabain selection pressure conferred ouabain resistance when transfected into ouabain-sensitive CV1 green monkey fibroblasts. Ouabain resistance was induced in the presence of 10 microM ouabain. Amiloride (500 microM) completely blocked ouabain-insensitive 86Rb+ uptake into these cells. Plasma membranes from these cells demonstrated little sodium-dependent adenosine triphosphatase (ATPase) activity but had potassium-dependent and ouabain-resistant p-nitrophenylphosphatase activity. Like Na+,K+-ATPase this activity was vanadate- and sodium-inhibitable. Also, like the Na+,K+-ATPase, sodium inhibition of the p-nitrophenylphosphatase was reversed by 10 microM adenosine 5'-triphosphate.
Hypertension 1987 Nov
PMID:Membrane biochemistry of the ouabain-resistant potassium transport system. 282 73

We assessed the role of putative circulating ouabainlike factor(s) on in vivo arteriolar function in rats with very early (less than 7 days; mean, 3 days) and chronic (greater than 4 weeks) benign, one-kidney, one clip (1K1C) hypertension. Thus, we measured vascular responses in vasodilated (nitroprusside or adenosine), vascularly isolated, innervated hindlimb vascular beds of chloralose-anesthetized 1K1C rats perfused with their own blood at 1 ml/min. Complete norepinephrine dose-response curves in 8 rats with chronic and 28 with early 1K1C hypertension, compared with appropriate normotensive control rats, showed unchanged thresholds and ED50 values. Magnitude of ouabain-induced leftward shifts of the norepinephrine dose-response curve in 18 rats with chronic and 21 with early 1K1C hypertension, compared with appropriate normotensive control rats, was unchanged. Blockade of neural uptake of norepinephrine by desimipramine (10(-7) M) in 8 1K1C rats did not alter these results. These findings provide no evidence in this form and these stages of hypertension that humoral ouabainlike inhibitors of the Na+-K+ pump evoke physiologically significant inotropic effects in arterioles in vivo. It is possible, however, that induction of vascular Na+-K+-adenosine triphosphatase by circulating inhibitors modified the vascular responses to norepinephrine and ouabain in these rats.
Hypertension 1987 Nov
PMID:The vascular Na+-K+ pump in experimental hypertension. 282 74

1. A ouabain-displacing factor (ODF) was measured in the urine of non-pregnant, normotensive pregnant and hypertensive pregnant women by a receptor-binding assay with sodium, potassium-dependent adenosine triphosphatase. 2. Urinary ODF was significantly increased in normal pregnancy. 3. Greater increases were seen in pregnancy-induced hypertension and pre-eclampsia.
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PMID:A ouabain-displacing factor in normal pregnancy, pregnancy-induced hypertension and pre-eclampsia. 283 Oct 7

The regulation of electrolytes has been proposed as a possible determinant in hypertensive conditions, including pregnancy-induced hypertension. We report a study of sodium/potassium-adenosine triphosphatase in erythrocyte membranes of 59 patients with pregnancy-induced hypertension and 48 normotensive pregnant controls. The kinetics of the enzyme were also investigated, and the enzyme activity related to different degrees of pathology. A marked reduction of the enzyme activity was found in hypertensive patients, compared with controls. This reduction was greater when hypertension was associated with worse prognostic signs, such as proteinuria. These features are in agreement with the increased sodium content and the increased vascular reactivity found in pregnancy-induced hypertension. The enzyme activity appears to be decreased by means of a conformational modification of the enzyme sites, a phenomenon related to the hypertensive condition.
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PMID:Sodium/potassium-adenosine triphosphatase on erythrocyte ghosts from pregnant women and its relationship to pregnancy-induced hypertension. 283 96

Sodium, potassium-adenosine triphosphatase (Na+, K+-ATPase) is hypothesized to be involved in systemic vascular hypertension through its effects on smooth muscle reactivity and myocardial contractility. By means of RNA blot analyses of cardiac, aortic, and skeletal muscle RNAs in two rat hypertensive models, Na+,K+-ATPase alpha-subunit messenger RNA isoforms (alpha 2 and alpha 3) were shown to be deinduced in response to increased intravascular pressure. The changes were observed after 48 hours or more of experimental hypertension. Under these conditions, there is coordinate induction of another alpha isoform (alpha 1) and of beta-subunit messenger RNAs, probably in response to alterations in sodium flux rather than to elevated blood pressure.
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PMID:Isoform-specific modulation of Na+, K+-ATPase alpha-subunit gene expression in hypertension. 283 7

We attempted to purify a digitalislike factor from human urine. On the assumption that a natural ligand for the digitalis receptor should be searched for on the basis of the effects on intact cells, we used an inhibitory effect on the binding of [3H]ouabain to human erythrocytes to determine digitalislike activity. A highly polar [3H]ouabain displacing activity was obtained by a combination of chromatographic procedures including reverse-phase high performance liquid chromatography. Urine-derived [3H]ouabain displacing activity, a competitive inhibitor of ouabain binding to human erythrocytes, acted on human lymphocytes in a similar manner. The dose-response curve of this compound was parallel to that of ouabain. Urine-derived [3H]ouabain displacing activity significantly inhibited monensin-stimulated increase in ouabain-sensitive 86Rb uptake, a parameter of Na+,K+-adenosine triphosphatase (ATPase), by 95% (p less than 0.01) in cultured vascular smooth muscle cells (A10 cells). Furthermore, this compound enhanced net 45Ca influx by 30% (p less than 0.01) and reduced 45Ca efflux by 35% (p less than 0.01) in A10 cells. These results suggest that urine-derived [3H]ouabain displacing activity may be a regulator of Na+,K+-ATPase and a modulator of vascular tone.
Hypertension 1988 Jun
PMID:The effects of urinary digitalislike factor on cultured vascular smooth muscle cells. 283 18

Free intracellular calcium was measured in renal proximal tubules obtained from spontaneously hypertensive rats (SHR) and from age-matched Wistar-Kyoto rats (WKY) ingesting a normal diet. Experiments were performed on renal proximal tubule suspensions using fura-2 to monitor cytosolic calcium. In 4-week-old rats, when systolic blood pressure was not significantly different between the two groups, renal proximal tubule cytosolic calcium was similar (143 +/- 28 and 144 +/- 15 nM, respectively). By the age of 5 weeks, cytosolic calcium increased significantly in both SHR and WKY (214 +/- 24 and 262 +/- 34 nM, respectively, p less than 0.05). Calcium, however, was not significantly different between the two groups, even though at this age blood pressure was higher in SHR than in WKY. As compared with values in 4-week-old rats, cytosolic calcium was also found increased in tubules from both SHR and WKY aged 10 to 12 weeks (261 +/- 42 and 279 +/- 30 nM, respectively) and 20 to 24 weeks (263 +/- 42 and 308 +/- 28 nM, respectively). However, no significant differences in cytosolic calcium were found between SHR and WKY even though at these ages systolic blood pressure increased markedly in the SHR. Moreover, regression analysis failed to reveal a correlation between cytosolic calcium and blood pressure when data from either group of rats of all ages studied were pooled. Exposure to ouabain (10(-3) M) to inhibit Na+,K+-adenosine triphosphatase and increase intracellular sodium had no significant effect on cytosolic calcium in tubules from either SHR or WKY (260 +/- 69 and 250 +/- 45 nM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1988 Oct
PMID:Free cytosolic calcium in renal proximal tubules from the spontaneously hypertensive rat. 284 68


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