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

We have compared the properties of beta-adrenergic receptors in slow-twitch, oxidative skeletal muscles (soleus) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at three different ages. The investigation was based on the hypothesis that the increase in Na+ content and decrease in fatigue resistance observed previously in the soleus of SHR might be the result of a down regulation of muscle beta-receptors. Activation of beta-adrenergic receptors in skeletal muscle stimulates sarcolemmal sodium-potassium adenosine triphosphatase, which produces an efflux of Na+ and an influx of K+. Receptor down-regulation would be expected to reduce hormonal stimulation of Na+ pump activity, particularly during exercise. The results of receptor binding studies, however, and an investigation of cyclic adenosine monophosphate (cAMP) production in response to applied epinephrine indicated that there were no significant differences in receptor properties in the soleus muscles of SHR and WKY rats. Receptor number and affinity were the same in the two strains, and the rate, magnitude, and duration of the increase in cAMP in response to 10(-6) M epinephrine were also similar. beta-Adrenergic receptor down-regulation does not appear to be a generalized phenomenon in tissues of SHR, despite the appearance of other physiological changes in the tissue.
Hypertension 1989 Jul
PMID:Beta-receptor properties in soleus muscles from spontaneously hypertensive rats. 254 28

An endogenous humoral factor which inhibits the sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) enzyme in vitro has been incriminated recently of playing a pathogenetic role in experimental and human hypertension. The present study was therefore performed in six healthy volunteers to investigate the hemodynamic consequences of an inhibition of this enzyme by ouabain, a potent and specific inhibitor of Na-K-ATPase. In addition, the role of intracellular calcium as a potential mediator was studied indirectly by the administration of nifedipine, a potent calcium entry blocker with predominant vasodilator properties. Intravenous administration of 8.5 micrograms ouabain/kg body weight inhibited red blood cell (RBC) - Na-K-ATPase by 49% which was accompanied by a significant increase in RBC - ATP and a decrease in intracellular potassium concentrations. This enzyme inhibition resulted in a 24% increase in peripheral vascular resistance. The parallel decrease in cardiac output and heart rate, however, prevented a rise in arterial pressure. This increase in vascular resistance was completely abolished by pretreatment with nifedipine (10 mg orally). In the absence of an effect of nifedipine on Na-K-ATPase, its attenuation of the vasoconstrictor effect of ouabain suggests that the effects of ouabain on the vascular smooth muscle cell are mediated by intracellular calcium. These results demonstrate that inhibition of the Na-K-ATPase enzyme in vivo causes a marked peripheral vasoconstriction. They are also compatible with the concept that an endogenous inhibitor of Na-K-ATPase - in the presence of decreased baroreceptor reflex sensitivity due to blood volume expansion - may play a role in the pathogenesis of human arterial hypertension.
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PMID:Studies on the role of sodium- and potassium-activated adenosine triphosphatase inhibition in the pathogenesis of human hypertension. Changes in vascular and cardiac function following inhibition of the sodium pump in normotensive subjects and effects of calcium entry blockade. 257 61

The mechanisms that define the relation between blood pressure and sodium handling are not yet well understood. Although several abnormalities in sodium transport have been associated with hypertension, a link between the blood pressure of normotensive subjects and the erythrocyte sodium-potassium adenosine triphosphatase pump, the principal sodium transporter of sodium, has not been previously demonstrated. Data from independent measurements of erythrocyte intracellular sodium, ouabain-sensitive sodium efflux, and the number of sodium pump sites per red blood cell were used to calculate a second-order rate constant for ouabain-sensitive sodium efflux. Among 20 normotensive white subjects, this rate constant correlated significantly (p less than 0.005) with mean arterial blood pressure. A significant correlation was not observed between the rate constant and the blood pressure of 22 hypertensive subjects. A hypothesis is proposed, which suggests that the sodium efflux rate constant of erythrocytes is related to the control of sodium reabsorption via the sodium pump of the renal tubules and that an elevated erythrocyte rate constant may be associated with chronic increased sodium reabsorption, which leads to volume expansion and the development of hypertension.
Hypertension 1989 Jun
PMID:Erythrocyte sodium transport and blood pressure in white subjects. 266 27

Dietary sodium intake has long been considered important in the genesis and maintenance of hypertension. This view is predicated on the results of epidemiologic observations, experiments in animals, investigations at the cellular level, and the results from dietary intervention trials. In the past decade a considerable body of new evidence has been gathered. A comprehensive, world-wide epidemiologic investigation involving over 10,000 subjects found significant relationships between sodium excretion and blood pressure levels and between sodium excretion and the slope of increase in blood pressure with age. The relationships, however, are not as straight-forward as previously proposed. Investigations in animals and in human subjects emphasize the genetic nature of salt sensitivity of blood pressure. A putative genetic marker has been suggested in human studies. At the cellular level, increases in sodium-lithium countertransport, sodium-hydrogen exchange, and cytosolic calcium level have been identified. Cytosolic calcium level was found to increase in lymphocytes in response to a high-salt diet in salt-sensitive individuals with hypertension, yet the identification of a circulating inhibitor of sodium-potassium--dependent adenosine triphosphatase remains elusive. Dietary intervention trials of salt restriction in patients with hypertension are generally disappointing. Active research is elucidating the role of sodium intake and hypertension at all levels. The data to date, however, still do not allow sweeping conclusions or generalizations.
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PMID:Salt and hypertension: recent advances and perspectives. 267 Dec 14

We studied the effect of hydrochlorothiazide, 50 mg daily, on Na,K-adenosine triphosphatase (ATPase) activity in the red cells of 10 black men with hypertension. We also examined net sodium and potassium movement in sodium-loaded, potassium-depleted, red cells. Treatment with hydrochlorothiazide resulted in a significant increase in mean ouabain-sensitive ATPase activity (+/- SEM) from 118.4 +/- 14.6 to 158.1 +/- 15.3 nmol phosphate released per milligram of protein (P = 0.0004). Ouabain-resistant ATPase did not change. Net sodium extrusion rose significantly, from 1.62 +/- 0.27 to 2.32 +/- 0.33 mmol/L/hr (P = 0.0275). We postulate that the enhanced activity of the Na,K pump results from the volume contraction induced by the diuretic. This interpretation is consistent with the concept that the Na,K pump is inhibited in volume expansion and volume-expanded hypertension. The finding of enhanced pump activity in subjects given treatment with hydrochlorothiazide suggests a possible mechanism of the antihypertensive action of diuretic therapy.
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PMID:Effect of treatment with hydrochlorothiazide on the red cell Na,K-adenosine triphosphatase in men with hypertension. 282 24

Na+,K+-adenosine triphosphatase (ATPase) inhibitors possessing inhibitory activities against the specific binding of ouabain to Na+,K+-ATPase and 86Rb uptake into hog erythrocytes have been purified from the plasma of hog acutely infused with saline. The purifications were performed by a combination of Amberlite XAD-2 adsorption chromatography and several steps of high performance liquid chromatography using four different types of columns. Inhibitors purified to homogeneity were identified as linoleic and oleic acids, gamma-stearoyllysophosphatidylcholine, gamma-arachidoyllysophosphatidylcholine, gamma-linoleoyllysophosphatidylcholine, and gamma-oleoyllysophosphatidylcholine. Small amounts of beta-arachidoyllysophosphatidylcholine, gamma-docosapentaenoyllysophosphatidylcholine, gamma-eicosatrienoyllysophosphatidylcholine, and gamma-palmitoyllysophosphatidylcholine were also detected by both fast atom bombardment mass and proton nuclear magnetic resonance spectrometric studies. Only gamma-acyllysophosphatidylcholines showed inhibitory activities on Na+,K+-ATPase and ouabain-binding activities. These lysophosphatidylcholines and unsaturated free fatty acids were effective at 100 microM levels in attaining 50% inhibition of the enzyme activity. The ouabain-displacing activity in plasma caused by these compounds increased with time during saline infusion. The maximal plasma levels of these components were approximately 10 times higher than that in the preinfusion plasma sample.
Hypertension 1987 Nov
PMID:Identification of Na+,K+-ATPase inhibitors of volume-expanded hog plasma. 282 59

We previously demonstrated that vascular smooth muscle cells possess a prominent Na+-K+-Cl- cotransport system that can be markedly stimulated by elevations in levels of intracellular cyclic guanosine 3',5'-monophosphate (cGMP). Since others have shown that atrial natriuretic factor (ANF) can bind to specific membrane receptors and can enhance cGMP levels in vascular smooth muscle cells, we asked whether ANF could also stimulate Na+-K+-Cl- cotransport in vascular smooth muscle cells. It was discovered that rat atriopeptin III stimulated Na+-K+-Cl- cotransport of vascular smooth muscle cells in a concentration-dependent manner. In contrast, rat atriopeptin III had no effect on two other sodium transport systems known to be present in vascular smooth muscle cells (i.e., Na+-H+ exchange and Na+-K+-adenosine triphosphatase (ATPase). These studies indicated that ANF selectively stimulates Na+-K+-Cl- cotransport of vascular smooth muscle cells. We then asked whether ANF-stimulated Na+-K+-Cl- cotransport was dependent upon the ability of ANF to enhance intracellular cGMP levels. When rat atriopeptin III-stimulated increases in cGMP were inhibited with the quinolinedione LY 83583, rat atriopeptin III could no longer stimulate Na+-K+-Cl- cotransport of vascular smooth muscle cells. Thus it appeared that the effects of ANF were dependent upon the ability of ANF to elevate intracellular cGMP levels. Finally, we asked whether ANF effects on Na+-K+-Cl- cotransport were related to the biological activity of ANF.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1987 Nov
PMID:Effect of atrial natriuretic factor on Na+-K+-Cl- cotransport of vascular smooth muscle cells. 282 61

Acute volume expansion, increased sodium intake, and restraint on sodium excretion endow the plasma with an increased capacity to inhibit sodium transport. Cytochemical techniques can detect the presence of Na+K+-adenosine triphosphatase (ATPase) inhibitor in the plasma of normal humans and rats, the concentration of which is controlled by salt intake. The substance responsible appears to originate in the hypothalamus, where the concentration is also controlled by salt intake. The plasma concentration of the cytochemically detectable Na+,K+-ATPase inhibitor is substantially raised in the plasma of patients with essential hypertension, spontaneously hypertensive rats (SHR) and of Milan hypertensive rats. The concentration of activity in the hypothalamus of SHR is also considerably raised. These findings demonstrate that these forms of hypertension are associated with a rise in the concentration of a cytochemically detectable circulating Na+,K+-ATPase inhibitor that under normal circumstances is controlled by salt intake.
Hypertension 1987 Nov
PMID:Ouabainlike Na+,K+-ATPase inhibitor in the plasma of normotensive and hypertensive humans and rats. 282 66

Plasma from volume-expanded and salt-loaded hypertensive animals and from patients with essential hypertension has been reported to inhibit Na+, K+-adenosine triphosphatase (ATPase). Inhibition of the sodium pump in vascular smooth muscle caused by such a circulating factor could increase vascular tone and sensitivity to vasoactive agents, and thereby result in arterial hypertension. Numerous efforts in the past failed to isolate the putative factor from urine and plasma. Recent studies have suggested that the hypothalamus is an important source of an endogenous Na+, K+-ATPase inhibitor, but its isolation from the tissue extracts has been rendered difficult by the presence of other cellular constituents that cause artifactual interference with the assays and purification procedures. Using an alternative approach of isolating the inhibitor from culture medium, we found that dispersed fetal rat hypothalamic neurons in a capillary culture system release a heat-stable, peptidic, low-molecular-weight, active sodium transport inhibitor that causes a reversible increase in vascular tone, sensitizes vascular smooth muscle to the vasoactive effect of norepinephrine, and possesses several characteristics of the putative endogenous digitalislike factor. This inhibitor may be a chemical mediator linking kidney, brain, and cardiovascular system in the genesis of experimental volume-expanded and salt-loaded hypertension and human essential hypertension.
Hypertension 1987 Nov
PMID:Problems and pitfalls in the isolation of an endogenous Na+, K+-ATPase inhibitor. 282 67

We characterized the effect of a small, nonpeptidic molecule isolated from bovine hypothalamus on mammalian Na+, K+-adenosine triphosphatase (ATPase). This hypothalamic factor has been shown to inhibit ATPase activity of purified dog kidney enzyme reversibly with high affinity. This report reviews the mechanism of inhibition. Hypothalamic factor inhibits Na+, K+-ATPase only from the extracellular surface. It prevents the phosphorylation from magnesium and inorganic phosphate of the active site aspartate residue of Na+, K+-ATPase and stabilizes the enzyme in an E2 conformation, preventing a sodium-induced shift from E2 to E1. Binding and dissociation reactions of hypothalamic factor in cultured renal tubular epithelial cells show a time frame different from that in isolated membranes and consistent with physiological relevance. A possible mechanism for the physiological regulation of Na+, K+-ATPase, including a cycle of binding and rapid dissociation in intact renal tubular cells, is discussed.
Hypertension 1987 Nov
PMID:Regulation of Na+, K+-ATPase by the endogenous sodium transport inhibitor from hypothalamus. 282 68


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