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PubMed1985

[Transmembrane effects in the sodium pump system. II. The ratio of the sodium efflux to the sodium concentration in frog muscle in media with various sodium substitutes].

The dependence of sodium efflux on the internal sodium concentration on sodium-free magnesium, Tris, coline and lithium media was investigated on frog striated muscle. In all the sodium-substituted media, the efflux concentration curve was found to be dependent on the external rubidium concentration, being S-shaped at the saturating external rubidium (potassium) concentration and becoming close to linear at the low external rubidium concentration (0.5-1.0 microM). The maximal sodium efflux at saturating levels of internal sodium concentrations remains unchanged with various sodium substitutes in the medium, whereas the affinity constant of internal sodium sites is dependent on the external cations.

Animals↗
PubMed1988

[Cation transport in murine L fibroblasts cultured long term in a serum-free medium].

Cation fluxes and intracellular content in mouse fibroblasts L, growing for more than three years in the Dulbecco modified Eagle's serum-free medium (clone L625sf) were measured as a function of culture density. The cells show no density-dependent inhibition of growth and in continuously growing cultures of L625sf cells internal potassium, and rubidium influx was found to remain high within a wide range of densities (5.10(4)-20.10(4) cells/cm2). A close correlation was revealed between the potassium transport and the proliferative state of L625sf cultures: the addition of 5% calf serum to logarithmically growing cultures leads to the increase in culture growth rate as well as to the increase in ouabain-inhibited rubidium influx and intracellular potassium content; a delay in culture growth rate due to medium depletion is accompanied by decreasing both the rubidium influx and the intracellular potassium content. It is concluded that L625sf cells being capable of multiplicating in serum-free medium remain sensitive to growth factors of serum and may be used for study of growth factor induction of cell proliferation and for identification of autocrine factors of cell growth.

Animals↗
PubMed1986

22Na and 86Rb effluxes from bull spermatozoa.

Active transport of sodium and potassium has been postulated for bull sperms by various authors. In the present paper the sodium and rubidium efflux was determined by tracer kinetics. For uninhibited sodium and rubidium efflux a rate constant of 8.9 +/- 2.13/min and 13.9 +/- 3.89 min, respectively, was found for a bull sperm suspension (20 vol.%, 310 K). After ouabain treatment (0.1 mM), a reduction of the rate constant of sodium efflux to 5.1 +/- 1.06/min was found. After cryopreserving (pelletizing process) the majority of samples investigated did not exhibit any inhibition of sodium and rubidium efflux as compared with fresh bull sperms. The inhibition of sodium efflux observed in some cases corresponds to the reduction of the rate constant of sodium efflux caused by ouabain. At storage in seminal plasma (24 h, 278 K) the rate constant of sodium efflux is reduced to 2.7 +/- 0.25/min. Both after ouabain treatment and after cryopreserving of sperms having a reduced rate constant the motility of bull sperms is reduced. It is concluded from the results that in bull sperms there exists an ouabain-sensitive sodium efflux, the inhibition of which reduces the rate constant of sodium efflux by 42%. The ouabain-sensitive sodium efflux is related to the motility of the bull sperm cell.

Animals↗
PubMed1981

[Changes in the alkaline cation transport across the plasma membrane of CHO-K1 cell lines resistant to ethidium bromide].

Sodium and potassium intracellular concentration, rate constants of sodium and potassium and rubidium influx were determined for cultured CHO-K1 cell lines, both sensitive and resistant to ethidium bromide. The emission technique was used to measure cation fluxes into potassium and sodium-free magnesium medium. Ethidium bromide sensitive and resistant cell have similar potassium concentrations, whereas sodium concentration in the latter is by almost 2.5 times higher than that in the former. A wide range of changes both in ouabain-sensitive and ouabain-resistant fluxes was found in resistant cells: the ouabain-inhibited rubidium influx is by 3-5 times lower, the ouabain-sensitive sodium efflux is practically absent, and ouabain-inhibited potassium efflux appears. In resistant cells the ouabain-insensitive influx of rubidium is decreased by almost 2 times. It is assumed that the selection of cells for resistance to ethidium bromide is accompanied by ":pleiothypic" changes of cell membrane, involving both active and passive cation transport.

Animals↗
PubMed1990

Photoinduction of cataracts in rat lens in vitro. Preventive effect of pyruvate.

Intact rat lenses were incubated in riboflavin-containing Tyrode solution or medium-199, generating photochemically active species of oxygen and the oxidative stress measured in terms of the decrease in active accumulation of rubidium, and the fall in the levels of glutathione and ATP. Addition of pyruvate to the medium prevented the tissue against oxidative damage as evidenced by a greater accumulation of rubidium and higher levels of glutathione and ATP. Pyruvate was thus found to be effective against the toxicity of oxygen derivatives, particularly the hydrogen peroxide. In dark experiments also, conducted in glucose-free medium, the uptake of rubidium was substantially greater in the presence of pyruvate. The levels of ATP were also higher. These results, therefore, suggest that this ketoacid is beneficial to the tissue through its ability to decompose H2O2 as well through providing a metabolic support. The development of in vitro cataract under the photochemical effects of riboflavin and oxygen was also effectively thwarted by pyruvate. The results are thus potentially useful from the point of view of developing pyruvate and similar compounds as effective anticataract agents.

Adenosine Triphosphate↗
PubMed1989

Blood flow distribution within transplantable tumours in the mouse.

Tumour blood flow was estimated by fractional distribution of rubidium in two allografts (B16 melanoma and Lewis lung tumour) and two xenografts (Glioma 522, a human grade IV astrocytoma and Mel-mo, a human melanoma), in order to investigate the influence of certain tumour characteristics on tumour perfusion. In all four tumours perfusion decreased with increase in tumour weight. The rubidium extraction in Mel-mo was markedly lower than that of the other three tumours; this tumour was the most necrotic. Necrosis was patchy in Glioma 522 and Mel-mo, but predominantly central in B16 and Lewis lung tumour. However, all tumour nodules examined showed a similar pattern of rubidium extraction: high at the rim with a rapid fall towards the centre. It appeared that while overall blood flow may be related to the extent of necrosis, blood flow distribution within tumour nodules did not correlate closely its pattern.

Animals↗
PubMed2005

Iron status influences trace element levels in human blood and serum.

Food is the main source of trace elements for the general population. The gastrointestinal absorption of certain trace elements, e.g., cadmium, is strongly influenced by iron (Fe) status. This factor may also be relevant for the bioavailability of other trace elements. Therefore, we investigated relationships between Fe status indicators and trace element concentrations in blood and serum of 234 boys and girls at ages 15 and 17 years. Fe status was measured using serum ferritin (S-Ft), soluble transferrin receptor in serum (sTfR), and the ratio sTfR/S-Ft. The trace elements we investigated were, in blood, cadmium, cobalt, copper, zinc, selenium, rubidium, mercury, and lead, and, in serum, cobalt, copper, zinc, selenium, rubidium, tungsten, mercury, and lead. We found inverse correlations between Fe status and blood cadmium, blood or serum cobalt, or blood copper. There were positive correlations between Fe status and mercury concentrations. Selenium was positively correlated with sTfR. The relationships between Fe status and lead were equivocal. There were fewer correlations for serum than for blood, but the inverse relationships between Fe status and cobalt were equally strong in serum and blood. We found only occasional, and perhaps spurious, correlations with zinc, rubidium, and tungsten. In conclusion, previous indications that cadmium, cobalt, and copper are absorbed by transport mechanisms similar to that of Fe are supported by this study. Strong positive correlations between Fe status and mercury concentrations remain to be explained.

Adolescent↗
PubMed2005

Evaluation of functional and binding assays in cells expressing either recombinant or endogenous hERG channel.

INTRODUCTION: The hERG (human ether-a-go-go related gene) potassium channel is required for normal cardiac repolarization, is susceptible to inhibition by a wide variety of compounds, and its blockage can lead to cardiac QT interval prolongation and life threatening arrhythmias. The present report examines the ability of hERG binding and functional assays to identify compounds with potential cardiovascular liabilities at the earliest stages of drug discovery. METHODS: Competitive binding assays were developed using (3)H-dofetilide and membranes from HEK293EBNA cells stably expressing recombinant hERG (HEK293-hERG) and IMR-32 cells expressing hERG endogenously. hERG functional assays were also developed using membrane potential indicator dye and rubidium efflux. The ability of these assays to identify compounds with potential adverse cardiac effects was examined using drugs with known cardiac effects ranging from those with no known adverse effects to drugs that were withdrawn from the market due to increased risk of sudden death associated with Torsades de Points. RESULTS: Binding assays using HEK293-hERG membranes and (3)H-dofetilide were robust (Z'=0.69+/-0.015, mean+/-S.E.M.), highly reproducible (test-retest slope=1.04, r(2)=0.98), and correlated well with IC(50) values obtained by patch clamp (slope=0.98, r(2)=0.89). Binding assays using IMR-32 membranes were less sensitive (Z'=0.4+/-0.03, mean+/-S.E.M., false negative rate=0.4) but still correlated well with patch clamp data (slope=1.06, r(2)=0.83). The hERG membrane potential assay could detect potent hERG inhibitors (defined by hERG patch clamp IC(50)<0.1 muM) using HEK293-hERG cells, but were prone to generate false-negative results with less potent inhibitors (false negative rate=0.5). Finally, the rubidium efflux assay gave highly reproducible results (Z'=0.80+/-0.02, mean+/-S.E.M.) that correlated with patch clamp IC(50) values (slope=0.87, r(2)=0.73). DISCUSSION: The hERG binding and rubidium efflux assays are robust, predictive of patch clamp results, and can be used at the earliest stages of drug discovery.

Animals↗
PubMed1987

Pharmacologic intervention as an alternative to exercise stress.

Although thallium exercise imaging has served an important role in clinical cardiology, it is significantly limited by suboptimal sensitivity and specificity, particularly in asymptomatic man. The increasing recognition of silent myocardial ischemia, the significant prevalence of coronary artery disease in asymptomatic middle age men, and the frequent occurrence of myocardial infarction without preceding symptoms in 60% of cases emphasizes the need for a more definitive, noninvasive diagnostic test for the presence of coronary artery disease suitable for screening in asymptomatic or symptomatic patients. Intravenous dipyridamole combined with handgrip stress provides a potent stimulus for purposes of diagnostic perfusion imaging. Although planar and single photon emission computed tomography (SPECT) imaging also have played an important role, these techniques are seriously hindered by their inability to quantitate radiotracer uptake or image modest differences in maximum relative flow caused by coronary artery stenosis. Accordingly, the combination of dipyridamole-handgrip stress with positron imaging of myocardial perfusion has become a powerful diagnostic tool suitable for routine clinical use. With the availability of generator-produced rubidium-82, dedicated clinically oriented positron cameras, the routine application of positron imaging to clinical cardiology has become feasible. Based on published literature, the current clinical indications for positron imaging that may be carried out economically on a routine clinical basis include assessment of myocardial perfusion utilizing rubidium-82 or N-13 ammonia for purposes of reliable, accurate, noninvasive screening for coronary artery disease in symptomatic or asymptomatic patients; assessing noninvasively the physiologic severity of coronary stenoses; myocardial infarct imaging; assessing myocardial viability of reversibly injured or ischemic cells using N-13 ammonia combined with fluorine-18-deoxy-glucose or Rubidium-82 alone in experimental animals; assessing regional or global left ventricle (LV) function by 3-dimensional gated blood pool imaging and/or wall thickening by ECG gating; and assessing the functional significance of collaterals in man.

Angiography↗
PubMed1999

Facile Synthesis and Structure of Heavy Alkali Metal Thiocarboxylates: Structural Comparison with the Selenium and Tellurium Isologues.

Potassium, rubidium, and cesium thiocarboxylates were found to be synthesized by the reaction of thiocarboxylic acid or its O-trimethylsilyl esters with KF, RbF, and CsF. Tetramethylammonium thiocarboxylates were prepared in good yields by the reaction of sodium thiocarboxylates with tetramethylammonium chloride. The structures of potassium benzene-, 2-methoxybenzene-, and 4-methoxybenzenecarbothioates, rubidium 2-methoxybenzenecarbothioate, tetramethylammonium 2-methoxy- and 2-trifluoromethylbenzenecarbothioates, potassium 2-methoxybenzenecarboselenoate, and rubidium 2-methoxybenzenecarbotelluroate were characterized by X-ray structural analysis. All of these alkali metal salts exhibit a dimeric structure in which the oxygen and/or sulfur atom is associated with the metal of the opposite molecule, while the tetramethylammonium thiocarboxylates are monomeric. In potassium 2-methoxybenzenecarbothioate, the two thiocarboxylate groups chelate to the potassium atoms above and below the plane which involves the thiocarboxylate groups. In potassium 4-methoxybenzenecarbothioate, one thiocarboxylate group chelates to potassium. Without exception, the o-methoxy oxygen intermolecularly coordinates to the metal of the opposite molecule. The C-O bond lengths of the thiocarboxylate group are in the range 1.22-1.24 Å, which is slightly longer than those of common thioesters. The C(sp(2))-S distances are in the range 1.70-1.72 Å, which is close to that of a typical C-S single bond and suggests that the negative charge may be somewhat localized on the sulfur atom. The interaction number of the metals with oxygen and sulfur atoms was 7 for K and 8 for both Rb and Cs. The dihedral angle between the thiocarboxyl group and the phenyl ring is substantially increased by the introduction of the o-methoxy group. In these alkali metal thio-, seleno-, and tellurocarboxylates, only cesium 2-methoxybenzenecarbotelluroate showed an intermolecular nonbonding interaction between the cesium and the phenyl ring carbons.

Journal Article↗
PubMed1995

Effects of chronic hyperfiltration on proximal tubule bicarbonate transport and cell electrolytes.

The compensatory response to unilateral nephrectomy (UNX) was investigated by a combination of renal clearance, microperfusion, electron microprobe, and morphological techniques. Filtration rate was significantly elevated 21 days following UNX and associated with a marked stimulation of bicarbonate and fluid absorption in the proximal tubule. Analysis of kinetic data of bicarbonate transport demonstrated strong flow-dependent activation of bicarbonate absorption in both control and experimental condition. The bicarbonate level at which half-saturation (apparent Kd) of transport occurred decreased uniformly at higher flow rates, but maximal transport rates (apparent Vmax) in the proximal tubule doubled in the remnant kidney. The flow dependence of bicarbonate transport in control and experimental conditions can be explained by an apparent unstirred layer effect modifying radial bicarbonate gradients in the tubule. Both Na/H-exchange and electrogenic H secretion contribute to bicarbonate absorption, but only Na/H-exchange increased significantly in proximal tubules of UNX rats. Cell ion concentrations after UNX were unchanged in cortical tubules, consistent with proportionately enhanced apical and basolateral ion transport. Proximal tubule cell rubidium concentration measured after a 30-second rubidium infusion as an index of basolateral Na,K-ATPase activity was unchanged in UNX rats. Inasmuch as cell volume increased significantly (25%), these data are consistent with a proportionate and similar stimulation of rubidium uptake and Na,K-ATPase activity.

Animals↗
PubMed2003

Clostridium botulinum C2 toxin: low pH-induced pore formation is required for translocation of the enzyme component C2I into the cytosol of host cells.

The binary Clostridium botulinum C2 toxin consists of two individual proteins, the transport component C2II (80 kDa) and the enzyme component C2I, which ADP-ribosylates G-actin in the cytosol of cells. Trypsin-activated C2II (C2IIa) forms heptamers that bind to the cell receptor and mediate translocation of C2I from acidic endosomes into the cytosol of target cells. Here, we report that translocation of C2I across cell membranes is accompanied by pore formation of C2IIa. We used a radioactive rubidium release assay to detect C2IIa pores in the membranes of Chinese hamster ovary cells. Pore formation by C2IIa was dependent on the cellular C2 toxin receptor and an acidic pulse. Pores were formed when C2IIa was bound to cells at neutral pH and when cells were subsequently shifted to acidic medium (pH < 5.5), but no pores were detected when C2IIa was added to cells directly in acidic medium. Most likely, acidification induces a change from "pre-pore" to "pore" conformation of C2IIa, and formation of the pore conformation before membrane binding precludes insertion into membranes. When C2I was present during binding of C2IIa to cells prior to the acidification step, C2IIa-mediated rubidium release was decreased, suggesting that C2I interacted with the lumen of the C2IIa pore. A decrease of rubidium efflux was also detected when C2I was added to C2IIa-treated cells after the acidification step, suggesting that C2I interacted with C2IIa in its pore conformation. Moreover, C2I also interacted with C2IIa channels in artificial lipid membranes and blocked them partially. C2I was only translocated across the cell membrane when C2IIa plus C2I were bound to cells at neutral pH and subsequently shifted to acidic pH. When cell-bound C2IIa was exposed to acidic pH prior to C2I addition, only residual intoxication of cells was observed at high toxin concentrations, and binding of C2I to C2IIa was slightly decreased. Overall, C2IIa pores were essential but not sufficient for translocation of C2I. Intoxication of target cells with C2 toxin requires a strictly coordinated pH-dependent sequence of binding, pore formation by C2IIa, and translocation of C2I.

Animals↗
PubMed1977

Ouabain-insensitive salt and water movements in duck red cells. I. Kinetics of cation transport under hypertonic conditions.

Duck red cells in hypertonic media experience rapid osmotic shrinkage followed by gradual reswelling back toward their original volume. This uptake of salt and water is self limiting and demands a specific ionic composition of the external solution. Although ouabain (10(-4)M) alters the pattern of cation accumulation from predominantly potassium to sodium, it does not affect the rate of the reaction, or the total amount of salt or water taken up. To study the response without the complications of active Na-K transport, ouabain was added to most incubations. All water accumulated by the cells can be accounted for by net salt uptake. Specific external cation requirements for reswelling include: sufficient sodium (more than 23 mM), and elevated potassium (more than 7 mM). In the absence of external potassium cells lose potassium without gaining sodium and continue to shrink instead of reswelling. Adding rubidium to the potassium- free solution promotes an even greater loss of cell potassium, yet causes swelling due to a net uptake of sodium and rubidium followed by chloride. The diuretic furosemide (10(-3)M) inhibits net sodium uptake which depends on potassium (or rubidium), as well as inhibits net sodium uptake which depends on sodium. As a result, cell volume is stabilized in the presence of this drug by inhibition of shrinkage, at low, and of swelling at high external potassium. The response has a high apparent energy of activation (15-20 kcal/mol). We propose that net salt and water movements in hypertonic solutions containing ouabain are mediated by direct coupling or cis-interaction, between sodium and potassium so that the uphill movement of one is driven by the downhill movement of the other in the same direction.

Animals↗
PubMed1998

The erythrocyte Na,K,Cl cotransporter and its circulating inhibitor in Dahl salt-sensitive rats.

BACKGROUND: Abnormal Na,K,Cl cotransport is thought to be a pathogenic factor in Dahl salt-sensitive rat models, but the only direct evidence for this is an increased cotransport activity found in erythrocytes from salt-loaded Dahl salt-sensitive rats. OBJECTIVE: To re-examine erythrocyte cotransport fluxes and a circulating cotransport inhibitory factor (CIF) in inbred Dahl rats maintained on a low (0.2%) salt diet. Cotransport fluxes were investigated both under basal conditions and after stimulation by cell shrinking. METHODS: Blood was drawn from 12 male Dahl salt-sensitive and 12 Dahl salt-resistant rats of the inbred John Rapp strain. Erythrocyte Na,K,Cl cotransport activity was equated to the bumetanide-sensitive fluxes of sodium, rubidium or lithium. Plasma CIF activity was tested in human erythrocytes. RESULTS: In Dahl salt-sensitive rats: (1) plasma CIF activity (5.7+/-0.4 units/ml) was modestly higher than in Dahl salt-resistant rats (2.97+/-0.12 units/ml, P < 0.0001), but much lower than that previously found in salt-loaded Dahl salt-sensitive rats (16.1 units/ml), and (2) erythrocytes exhibited a similar bumetanide-sensitive sodium efflux (rate constant 0.056+/-0.008 h(-1)) as in Dahl salt-resistant rats (0.047+/-0.007 h(-1)). Following hypertonic shock, the bumetanide-sensitive rubidium influx reacted more to cell shrinkage in Dahl salt-sensitive than in Dahl salt-resistant erythrocytes (cell volume decrease required to stimulate bumetanide-sensitive rubidium influx by 4000 micromol/l cells per h=-4.04+/-0.36 versus -5.89+/-0.44 fl, respectively; P< 0.01). CONCLUSIONS: When fed a low-salt diet, Dahl salt-sensitive rats present slightly increased plasma CIF levels and normal erythrocyte cotransport fluxes under basal conditions, but an increased response to a hypertonic shock. Therefore, if there is any primary cotransport abnormality in Dahl salt-sensitive rats, it appears to be restricted to the renal Na,K,Cl cotransporter BSC1 isoform. Alternatively, any such change may be the consequence of abnormal regulation by osmolarity-dependent mechanisms.

Animals↗
PubMed2003

Phase transitions in KTP isostructures: correlation between structure and Tc in germanium-doped RbTiOPO4.

Crystals of germanium-doped rubidium titanyl phosphate, Rb(2)(Ti)(Ge(0.121)Ti(0.879))O(2)(PO(4))(2) (GeRTP#1) and Rb(2)(Ge(0.125)Ti(0.875))(Ge(0.225)Ti(0.775))O(2)(PO(4))(2) (GeRTP#2), have been structurally characterized from X-ray diffraction data at room temperature. In addition, a third structure, Rb(2)(TiO)(2)(PO(4))(2) (RTP), has been reinvestigated. The exchange of titanium for germanium results in a less distorted octahedral coordination around the two crystallographically independent titanium sites. Additionally, rubidium split-cation positions have been found in these doped RTP crystals. Dielectric measurements show that the phase-transition temperature, T(c), decreases with increasing germanium concentration, and a direct correlation between the room-temperature split of the rubidium cations and T(c) has been discovered. General trends regarding the relationship between the room-temperature structures of KTP-like compounds and their T(c) values are discussed.

Journal Article↗
PubMedDate not supplied

Cytopathic action of Naegleria fowleri amoebae on rat neuroblastoma target cells.

The axenically cultured, weakly pathogenic Naegleria fowleri LEE and the highly pathogenic, mouse passaged N. fowleri LEEmp are cytopathic for B103 rat nerve cells in culture. Cytopathogenicity was measured by release of radiolabeled rubidium or radiolabeled chromium from B103 target cells. Cytopathogenicity was time-dependent for up to 18 h and dependent upon amoebae effector to nerve cell target ratios of less than 1:1. Release of 51Cr from B103 cells by either LEE or LEEmp amoebae was enhanced by addition of calcium or magnesium to medium free of these divalent cations but the ion-channel inhibitor, verapamil, or the ionophore A23187 and phorbol myristate acetate did not alter release of 51Cr from B103 cells cocultured with the amoebae. Cycloheximide or actinomycin D impaired release of 51Cr from B103 target cells injured by either LEE or LEEmp amoebae. Both strains of amoebae were fractionated by glass bead disruption and high speed centrifugation into membrane and soluble fractions. Each fraction was incubated with either 86Rb or 51Cr labeled nerve cells. The membrane fraction from LEEmp was more active than the soluble fraction in facilitating rubidium and chromium release. In contrast, the soluble fraction from LEE was more active than the membrane fraction in facilitating rubidium release from radiolabeled target cells. The sequential release of 86Rb and 51Cr from target cells rather than the simultaneous release of the two isotopes indicates that target cell death is due to the release of ions followed later by the release of large macromolecules. The results indicate that N. fowleri amoebae injure nerve cells by two alternate mechanisms, trogocytosis or contact-dependent lysis.

Animals↗
PubMed1982

Inhibition of the sodium pump by inorganic phosphate in resealed red cell ghosts.

1. Ouabain-sensitive Rb influx was measured into K-free resealed red cell ghosts. The effects of inorganic phosphate (Pi) were examined. 2. Phosphate decreased the magnitude of the influx. Increasing Pi lowered the apparent affinity for both ATP and external rubidium ions. The effects of Pi on the affinity for external Rb were greatest at low ATP concentrations. 3. In the nominal absence of phosphate, increasing ATP from 1 to 100 microM had little effect on the Rb influx from solutions of low (1 microM) rubidium concentrations. In the presence of Pi, ATP increased Rb uptake markedly, even from solutions of low Rb concentration. 4. The above interactions between Pi, ATP and external Rb are consistent with a consecutive scheme for the Na pump in which phosphate is released after potassium binds at the external surface and before ATP binds to release potassium ions to the internal solution. 5. Previous failures to find an effect of phosphate on either the affinity for ATP or that for external potassium (rubidium) ions are shown to be equally consistent with the model. The lack of change of apparent affinity is shown to result from the restricted range of concentrations used in these previous experiments.

Adenosine Triphosphate↗
PubMed1990

Deuterium oxide normalizes blood pressure and vascular calcium uptake in Dahl salt-sensitive hypertensive rats.

This study examined the effect of 25% deuterium oxide in drinking water on systolic blood pressure, uptakes of calcium, and rubidium 86 by aortas of Dahl salt-sensitive rats on 0.4% (low) and 8% (high) sodium chloride (salt) diet. Twenty-four rats were divided into four groups. Groups I and II were on the low salt diet and groups III and IV on the high salt diet from 6 weeks of age. Additionally, at 10 weeks of age groups I and III were placed on 100% water and groups II and IV on 25% deuterium oxide. At 14 weeks, systolic blood pressure, uptakes of calcium, and rubidium 86 by aortas were significantly higher (p less than 0.01) in rats on the high salt diet as compared with those on the low salt diet. Deuterium oxide intake normalized systolic blood pressure and aortic calcium uptake but not aortic rubidium 86 uptake in hypertensive rats on the high salt diet. Deuterium oxide had no effect on blood pressure or aortic calcium uptake in rats on the low salt diet. The parallel increase in systolic blood pressure and vascular calcium uptake suggests that increased calcium uptake mechanisms are associated with hypertension in salt-sensitive Dahl rats. Furthermore, deuterium oxide appears to normalize elevated blood pressure in salt-sensitive hypertensive rats by normalizing elevated vascular (aortic) calcium uptake.

Animals↗