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

Renal nerve activity increases (Na+, K+)-ATPase activity and contributes to the development of hypertension in young SHR. The present study was designed to examine the effect of sodium intake on blood pressure and proximal tubule solute reabsorption in sham-operated or renal denervated, 5-week old SHR and WKY. Three-week old SHR and WKY rats underwent sham surgery or renal denervation with 10% phenol and were maintained for 10 days on either a 0.6% or 2.2% NaCl diet. Blood pressure was obtained by indirect tail cuff measurements during this interval. Of the eight groups, only sham-operated SHR on a high sodium diet had hypertension, 122.0 +/- 4.2 mm Hg vs. 98.7 +/- 3.3 mm Hg (mean for remaining groups). Renal plasma flow (RPF), glomerular filtration rate (GFR), and the fractional excretion of lithium (FELi) were determined in rats maintained on a 2.2% sodium diet at 5 weeks of age. FELi was less in sham-operated SHR, 5.3 +/- 0.7%, compared to WKY, 9.4 +/- 2.8% (P less than 0.02). Furthermore, denervation ameliorated the reduced FELi in SHR, 10.2 +/- 1.2%, without affecting FELi in WKY. RPF and GFR were similar between sham-operated and renal denervated SHR and WKY. No significant difference could be detected in net sodium balance between WKY and SHR during this period. These findings demonstrate 1) from the basis of FELi, young SHR, of this strain, exhibit enhanced proximal tubule solute reabsorption and hypertension while on a high sodium diet and, 2) renal denervation ameliorates both the enhanced proximal tubule solute reabsorption and the early development of hypertension. These data support the concept that renal nerve activity of young SHR is augmented and contributes to the development of hypertension by enhancing salt retention.
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PMID:Renal nerve-mediated proximal tubule solute reabsorption contributes to hypertension in spontaneously hypertensive rats. 162 13

In previous reports, we described the isolation and characterization of an endogenous digitalislike factor (EDLF). In this report, we describe a unique combination of bioassay and large-scale purification methodology that made possible the purification of sufficient quantities of this inhibitor of Na+,K(+)-ATPase for structural analysis. Using an initial XAD-2 extraction and preparative high-performance liquid chromatography followed by a batch enzyme affinity extraction and two subsequent semipreparative chromatographic steps, 300 l of human plasma was processed, yielding 31 micrograms (53 nmol) of pure EDLF and representing purification on a dry weight basis in excess of 0.6 billionfold. Four divergent pieces of evidence, including chromatographic, mass spectrometric, immunoreactive, and binding characteristics, suggested that the EDLF purified in the present study was either ouabain or an isomer of ouabain. This material may represent a plasma-borne, naturally occurring, selective, high-affinity ligand for the digitalis binding site that may play a significant role in the modulation of the sodium pump and thereby cellular electrolyte homeostasis in humans.
Hypertension 1991 Jun
PMID:Purification of an endogenous digitalislike factor from human plasma for structural analysis. 164 71

By altering the Na+/K+ electrochemical gradient, Na+,K(+)-ATPase activity profoundly influences cardiac cell excitability and contractility. The recent finding of mineralocorticoid hormone receptors in the heart implies that Na+,K(+)-ATPase gene expression, and hence cardiac function, is regulated by aldosterone, a corticosteroid hormone associated with certain forms of hypertension and classically involved in regulating Na+,K(+)-ATPase gene expression and transepithelial Na+ transport in tissues such as the kidney. The regulation by aldosterone of the major cardiac Na+,K(+)-ATPase isoform genes, alpha-1 and beta-1, were studied in adult and neonatal rat ventricular cardiocytes grown in defined serum-free media. In both cell types, aldosterone-induced a rapid and sustained 3-fold induction in alpha-1 mRNA accumulation within 6 h. beta-1 mRNA was similarly induced. alpha-1 mRNA induction occurred over the physiological range with an EC50 of 1-2 nM, consistent with binding of aldosterone to the high affinity mineralocorticoid hormone receptor. In adult cardiocytes, this was associated with a 36% increase in alpha subunit protein accumulation and an increase in Na(+)-K(+)-ATPase transport activity. Aldosterone did not alter the 3-h half-life of alpha-1 mRNA, indicating an induction of alpha-1 mRNA synthesis. Aldosterone-dependent alpha-1 mRNA accumulation was not blocked by the protein synthesis inhibitor cycloheximide, whereas amiloride inhibited both an aldosterone-dependent increase in intracellular Na+ [Na+]i) and alpha-1 mRNA accumulation. This demonstrates that aldosterone directly stimulates Na+,K(+)-ATPase alpha-1 subunit mRNA synthesis and protein accumulation in cardiac cells throughout development and suggests that the heart is a mineralocorticoid-responsive organ. An early increase in [Na+]i may be a proximal event in the mediation of the hormone effect.
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PMID:Aldosterone-mediated regulation of Na+, K(+)-ATPase gene expression in adult and neonatal rat cardiocytes. 164 19

A crucial role of humoral factors in the pathogenesis of primary hypertension is discussed. In 1982 Hamlyn et al demonstrated the presence of a Na+, K(+)-ATPase inhibitor in the plasma of essential hypertensives and showed a significant correlation of the Na+, K(+)-ATPase inhibition with the blood pressure. In this study we examined whether an Na+, K(+)-ATPase inhibitor could be found in the blood of essential hypertensives as compared to patients with secondary hypertension (renal hypertension, renal artery stenosis, pheochromocytoma). Second, the possible correlation between an inhibition of Na+, K(+)-ATPase and the intracellular electrolyte composition was examined. The results demonstrate a similar reduction of Na+, K(+)-ATPase inhibition in both essential hypertensives and secondary hypertensives as compared to normotensive controls. Further, the intracellular electrolyte composition (Na+, Na; K+, Ca) does not show a significant correlation to the degree of Na+, K(+)-ATPase inhibition, whereas a significant correlation between the degree of Na+, K(+)-ATPase inhibition and intracellular Cl- concentration could be demonstrated. The present study shows that an endogenous Na+, K(+)-ATPase inhibitor is also present in secondary forms of hypertension, thus implying that a specific role in the pathogenesis of primary hypertension for an Na+, K(+)-inhibitor is unlikely.
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PMID:Na+, K(+)-ATPase inhibition and intracellular electrolyte content in essential and secondary hypertension. 164 95

Plasma from normal humans and rats on a high sodium intake, and from patients and rats suffering from hereditary hypertension has an increased cytochemically detectable glucose-6-phosphate dehydrogenase (G6PD)-stimulating/Na-K-ATPase inhibiting activity. The hypothalamic content of this activity is also increased by a high sodium intake and in the spontaneously hypertensive rat (SHR). Using cytochemical techniques, the ability of plasma and the hypothalamus of reduced renal mass hypertensive rats to stimulate G6PD activity and to inhibit Na-K-ATPase was measured. The mean G6PD-stimulating capacity of the plasma from the hypertensive and normotensive groups of rats was 351 +/- 67 and 11.42 +/- 1.98 G6PD-stimulating units/mL respectively (P less than .001). The time courses of the ability of plasma from a hypertensive and a normotensive rat to inhibit fresh tissue Na-K-ATPase after 2, 4, 6, and 8 min of exposure demonstrated that the hypertensive rat plasma had a greater capacity to inhibit Na-K-ATPase. The mean G6PD-stimulating capacity of the hypothalamus from the hypertensive and normotensive groups of rats was 252,263 +/- 147,958 X 10(3) and 6.38 +/- 2.35 X 10(3) G6PD-stimulating units per hypothalamus, respectively (P less than .01). It is proposed that the raised concentration of cytochemically detectable G6PD-stimulating/Na-K-ATPase-inhibiting substance in both genetic and nongenetic forms of hypertension may be a manifestation of a communal hypertensinogenic mechanism. Thus, the raised plasma concentration would have a direct peripheral vascular constricting effect and the high hypothalamic concentration would be responsible for a central nervous hypertensinogenic effect.
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PMID:Cytochemically detectable glucose-6-phosphate dehydrogenase-stimulating/Na-K-ATPase-inhibiting activity of plasma and hypothalamus in reduced renal mass hypertension. 164 96

The plasma membrane sodium-potassium pumps that regulate intracellular sodium in most animal cells have specific, high-affinity receptors for the digitalis glycosides and their aglycones. This has fostered speculation that there is an endogenous ligand. We have purified and structurally identified by mass spectroscopy an endogenous substance from human plasma that binds with high affinity to this receptor and that is indistinguishable from the cardenolide ouabain. This human ouabain-like compound (OLC) displaces [3H]ouabain from its receptor, inhibits Na,K-ATPase and ouabain-sensitive 86Rb+ uptake, and has cardiotonic actions quantitatively similar to commercial ouabain. Immunoreactive OLC was detected in the plasma of many mammals, and high concentrations were found in the adrenals. The circulating OLC may modulate intracellular Na+ and affect numerous Na+ gradient-dependent processes including intracellular Ca2+ and pH homeostasis in many tissues. Furthermore, altered circulating levels of OLC may be associated with the pathogenesis of certain forms of hypertension.
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PMID:Identification and characterization of a ouabain-like compound from human plasma. 164 35

To evaluate the importance of an endogenous sodium pump inhibitor in the pathogenesis of low renin human hypertension, the urinary excretion of a digoxin-like immunoreactive substance (DLIS) was measured in eight patients with primary aldosteronism (n = 5, with adenomas) during two sequential 1-week periods of low- (20 mmol/l NaCl) and high- (200 mmol/l NaCl) sodium intake. DLIS excretion increased consistently during high-sodium intake while urinary aldosterone, plasma renin activity, cortisol and adrenocorticotropic hormone did not change. Although blood pressure showed a time-course parallel to that of the urinary DLIS, the blood pressure increments were not accompanied by evidence of vasoconstriction since forearm blood flow (plethysmographic technique) increased and forearm vascular resistances were reduced. Moreover, the reactivity of forearm arterioles to local norepinephrine was unchanged during the period of low- and high-salt intake, despite the fact that an endogenous sodium pump inhibitor should, supposedly, sensitize the responses to an adrenergic agonist. Finally, forearm vasoconstrictor responses to ouabain, a pharmacological Na+,K(+)-ATPase antagonist, were potentiated during the high-salt diet, a result not expected if an increased number of sodium pumps were occupied by an endogenous inhibitor. These results provide unequivocal evidence for a modulation by salt intake of the urinary excretion of a DLIS in patients with primary aldosteronism. This substance might participate in the regulation of body fluid volume in this syndrome and possibly in other physiological conditions. However, no evidence could be found for a cause--effect relationship between blood pressure and DLIS increments during high-salt intake, at least during the short-term course of the study.
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PMID:Does a digoxin-like substance participate in vascular and pressure control during dietary sodium changes in patients with primary aldosteronism? 164 66

The imbalance of cation transport is considered to play an important role in the development of hypertension, and this also applies to hypertension during pregnancy. Magnesium (Mg) is one of the factors that regulate cation transport across the cell membrane. We therefore studied the effect of a magnesium-deficient diet on the activity of erythrocyte Na/K-ATPase and Mg-ATPase from six pregnant rabbits and compared the results to those obtained from six controls on a normal diet. None of the rabbits on the deficient diet developed hypertension or intrauterine growth retardation; nevertheless the activity of both enzymes was significantly reduced compared to the group on the normal diet. Since the reduced activity of these enzymes can determine sodium or calcium retention in the cell, Mg deficiency could be the basis of the onset of some forms of hypertension in pregnancy.
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PMID:Effect of magnesium-deficient diet on cation transport in pregnant rabbits. 165 May 73

Recent studies about renal function and volume regulating hormones in obstructive sleep apnea (oSAS) indicate complex disturbances in volume homeostasis. Increased nocturnal secretion of atrial natriuretic peptide (ANP) and decreased renin secretion during apnea looks similar to a situation seen during hypervolemia or increased cardiac volume load. Increased venous return induced by pathologically high negative intrathoracic pressure during obstructive apnea may be the cause. Since during wakefulness no true hypervolemia is present, a "pseudohypervolemia" or "central hypervolemia" must exist caused by volume shift from the peripheral to the central compartment during apnea. Since volume homeostasis and blood pressure regulation are complexly connected the question arises whether disturbances in volume homeostasis play a role in the pathogenesis of arterial hypertension in sleep apnea. In a subgroup of hypertensive patients hypertension is salt-sensitive and volume dependent; it is called volume-expanded or low-renin hypertension. An inhibitor of the Na+/K(+)-ATPase acting via the digitalis receptor - called digitalis like factor (DLF) - is regarded as the causative agent for the development of hypertension in these cases. From this background, we were interested in the question whether DLF may be the linkage between disturbances in volume homeostasis and the pathogenesis of hypertension in sleep apnea. We could demonstrate a decrease of nocturnal urinary excretion of DLF during nasal continuous positive air pressure (nCPAP) therapy. Since a positive correlation between changes in diuresis respectively natriuresis and DLF excretion was found, we suggested DLF to be involved in changes of renal function in sleep apnea besides ANP. In 3 patients we measured nocturnal plasma levels of DLF and renin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disturbances in volume regulating hormone system--a key to the pathogenesis of hypertension in obstructive sleep apnea syndrome? 165 Sep 45

Endogenous digital-like substance (DLS) is increased in patients with essential hypertension and is hypothesized to play a role in the pathogenesis of high blood pressure. Whether an increase in DLS in diabetic patients with hypertension is associated with a family history of hypertension or diabetic nephropathy was investigated. Plasma DLS was measured as Na(+)-K(+)-ATPase inhibitory activity (ATPI) in 100 Type 2 diabetic patients. Ouabain was used as a standard of Na-K-ATPase inhibition. Diabetic patients with hypertension demonstrated a greater ATPI level than normotensive diabetic patients (p less than 0.05). In patients with hypertension groups, the positive family history group had a higher ATPI level than the negative family history group (p less than 0.01). Microalbuminuria was not correlated with the ATPI level in diabetic patients. These results suggest that ATPI might play a role in the pathogenesis of hereditary hypertension associated with diabetes mellitus, but not have etiologic significance in diabetic nephropathy.
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PMID:Elevated endogenous digitalis-like substance in hypertensive diabetic patients with a family history of hypertension. 165 64


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