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Effects of antiglucocorticoids on glucocorticoid hypertension in the rat.

The early phase of hypertension induced in rats by a glucocorticoid agonist RU 26988 was studied. Systolic blood pressure increased by 35 mm Hg. Water and sodium urinary excretion increased transiently, and plasma volume decreased. Total and ouabain-sensitive sodium efflux, as well as rubidium efflux, were enhanced by glucocorticoid administration. Low salt intake did not prevent hypertension. Pretreatment with RU 38486, a steroid with antiglucocorticoid properties, largely prevented the rise in blood pressure (+10 mm Hg) and suppressed transient natriuresis and the decrease in plasma volume. Changes in total and ouabain-sensitive sodium efflux were completely prevented, whereas changes in rubidium efflux were only partly reversed. Similarly, administration of progesterone, a steroid with antiglucocorticoid effects, prevented glucocorticoid hypertension (+11 mm Hg) and vascular ionic changes. In contrast administration of RU 28318, an antimineralocorticoid agent, was without effect on glucocorticoid hypertension (+38 mm Hg). Progesterone or RU 38486 administered after glucocorticoid also decreased blood pressure. Present data indicate that glucocorticoid hypertension may be prevented or reversed in its early phase by steroid drugs with antiglucocorticoid properties. These drugs also appeared to prevent the sodium and rubidium flux abnormalities induced by glucocorticoid. We suggest that activation of the vascular glucocorticoid receptors may be involved in the pathophysiology of glucocorticoid hypertension.

Androstanols↗

Low-temperature polarized helium-3 for MRI applications.

The first 3He nuclear magnetic resonance (NMR) experiments using low-temperature prepolarization are presented. 3He cells were polarized at 4.2 K and 4.7 T, transported to another magnet, heated to room temperature, and used for NMR experiments at 2.35 T. Cells with and without a rubidium coating were tested. In both cases, the NMR signal was greater than 100 times the thermal equilibrium signal. No evidence of a rubidium coating effect on the longitudinal relaxation time T1 of 3He (500 mbar) at 4.2 K could be demonstrated. NMR gradient-echo images of the cells were acquired.

Helium↗

Metallic content of wines from the Canary Islands (Spain). Application of artificial neural networks to the data analysis.

Eleven elements, K, Na, Ca, Mg, Fe, Cu, Zn, Mn, Sr, Li and Rb, were determined in dry and sweet wines bearing the denominations of origin of El Hierro, La Palma and Lanzarote islands (Canary Islands, Spain). Analyses were performed by flame atomic absorption spectrophotometry, with the exceptions of Li and Rb for which flame atomic emission spectrophotometry was used. The content in copper and iron did not present risks of cases. All samples presented a copper and zinc content below the maximum amount recommended by the Office International de la Vigne et du Vin (OIV) for these elements. Significant differences in the metallic content were found among the different islands. Thus, Lanzarote presented the highest mean content in sodium and lithium and the lowest mean content in rubidium, and La Palma presented the highest mean content in strontium and rubidium. Sweet wines from La Palma, elaborated as naturally sweet with over-ripe grapes, presented mean contents significantly higher with regard to dry wines from the same island in the majority of the analysed elements. Cluster analysis and Kohonen self-organising maps showed differences in wines according to the island of origin and the ripening state of the grapes. Back-propagation artificial neural networks showed better prediction ability than stepwise linear discriminant analysis.

Atlantic Islands↗

Ion-transporting activity in the murine colonic epithelium of normal animals and animals with cystic fibrosis.

Electrogenic ion transport in the isolated colonic epithelium from normal and transgenic mice with cystic fibrosis (CF mice) has been investigated under short-circuit current (Isc) conditions. Normal tissues showed chloride secretion in response to carbachol or forskolin, which was sensitive to the Na-K-2Cl cotransport inhibitor, frusemide. Responses to both agents were maintained for at least 12 h in vitro, but the responses to carbachol changed in format throughout this period. By contrast CF colons failed to show the normal secretory responses to carbachol and forskolin, most preparations showing a decrease in Isc that was immediately reversed by frusemide. In CF colons addition of Ba2+ ions or tetraethylammonium (TEA+) to the apical bathing solution antagonised the reduction in Isc caused by the secretagogues. It is concluded that the reduction in Isc in CF colons is due to electrogenic K+ secretion and this was confirmed by flux studies using rubidium-86. In normal colons exposed to TEA+ the responses to forskolin were greater, but not significantly so, presumably because the minor K(+)-secretory responses are dominated by major chloride-secretory responses. Again rubidium-86 fluxes showed an increase of K+ secretion in normal colons receiving forskolin. Since the amiloride-sensitive current was not different in CF and normal colons there was no evidence that the CF mice were stressed in a way that increased mineralocorticoid levels and hence K+ secretion. Knowledge of the phenotype of the colonic epithelium of the CF mouse sets the baseline from which attempts at gene therapy for the gut must be judged.

Amiloride↗

Studies on potassium induced coronary dilation in the isolated guinea pig heart.

Changes of coronary flow in the isolated perfused spontaneously beating guinea pig heart were induced by elevation of potassium concentration in the perfusion medium (4-16 meq/l). Potassium caused a dose-dependent transient increase of diastolic coronary inflow. The response was inhibited by ouabain (1.4 X 10(-7) M) or reduced temperature. Rubidium ions elicited almost identical vasodilator effects which were also inhibited by ouabain. Autoregulation of coronary flow, reactive hyperemia, and hypoxic coronary dilation were not significantly altered in the presence of ouabain. The results support the hypothesis that potassium as well as rubidium cause vasodilation by activating a Na+, K+-ATPase. On the other hand, they do not favour the view of an essential involvement of potassium ions in local regulation of coronary flow under the conditions studied.

Animals↗

Ammonium transport in medullary thick ascending limb of rabbit kidney: involvement of the Na+,K+,Cl(-)-cotransporter.

In order to investigate the question whether ammonium reabsorption in the thick ascending limb of Henle's loop (TALH) proceeds via the Na+,K+,Cl(-)-cotransporter, plasma membrane vesicles were prepared from TALH cells isolated from rabbit kidney outer medulla and the effect of NH+4 on their transport properties was investigated. It was found that, in the presence of a 78-mmol/liter NaCl gradient, 5 mmol/liter NH+4 inhibited bumetanide-sensitive rubidium flux by 86%; a similar decrease was observed for 5 mmol/liter, K+. Inhibition of bumetanide-sensitive rubidium uptake by NH+4 was competitive and an apparent Ki of 1.9 mmol/liter was found. Bumetanide-sensitive sodium uptake measured in the presence of a 83 mmol/liter KCl gradient was not inhibited by 5 mmol/liter NH+4. A 100-mmol/liter NH4Cl gradient was, however, capable of stimulating bumetanide-sensitive sodium uptake to the same extent as a KCl gradient. These data suggest that NH+4 is accepted by the K+ site of the Na+,K+,Cl-cotransport system and that the transporter can function in a Na+,NH+4,2Cl mode. Since the affinity of the transporter for NH+4 lies in the concentration range found in the TALH lumen in vivo, it is concluded that Na+,NH+4,2Cl-cotransport can contribute to the NH+4 reabsorption in this tubular segment.

Ammonia↗

Effects of magnesium and terbutaline on contractility and K+ uptake in isolated human uterine muscle.

Mg++ (3 and 6 mmol/L), the beta 2-adrenergic agonist terbutaline (1 and 10 mumol/L), and dibutyryl cyclic adenosine 5'-monophosphate (0.1 and 1 mmol/L) suppressed spontaneous activity and the increase in contractile activity induced by ouabain or K(+)-free buffer in isolated human pregnant myometrium. The ouabain-suppressible rubidium 86 or potassium 42 uptake was unaffected by the presence of Mg++ (3 and 6 mmol/L), the beta 2-adrenergic agonist terbutaline (1 and 10 mumol/L), or dibutyryl cyclic adenosine 5'-monophosphate (1 mmol/L). However, loading of the strips with Na+ and incubation in high K+ induced a fivefold increase in rubidium 86 uptake. On the basis of these flux rates, our previous data on the total concentration of sodium-potassium pumps in the human myometrium, and an estimated maximum transport rate of the sodium-potassium pump of 8900 K+ ions per minute at 30 degrees C, it could be calculated that the sodium-potassium pump in the Na(+)-loaded strips reached around 80% of its maximal rate. Taken together, these results showed that the relaxant effects of Mg++, terbutaline, and dibutyryl cyclic adenosine 5'-monophosphate on human myometrium are not due to a stimulation of active sodium-potassium transport.

Biological Transport↗

Monovalent cations and inorganic phosphate alter branched-chain alpha-ketoacid dehydrogenase-kinase activity and inhibitor sensitivity.

Potassium ion protects the branched-chain alpha-ketoacid dehydrogenase complex against inactivation by thermal denaturation and protease digestion. Rubidium was effective but sodium and lithium were not, suggesting that the ionic size of the cation is important for stabilization of the enzyme. Thiamine pyrophosphate stabilization of the complex [Danner, D. J., Lemmon, S. K., and Elsas, S. J. (1980) Arch. Biochem. Biophys. 202, 23-28] was found dependent on the presence of potassium ion. Studies with resolved components indicate that the thiamine pyrophosphate-dependent enzyme of the complex, i.e., the 2-oxoisovalerate dehydrogenase (lipoamide) (EC 1.2.4.4), is the component stabilized by potassium ion. Branched-chain alpha-ketoacid dehydrogenase-kinase activity measured by inactivation of the branched-chain alpha-ketoacid dehydrogenase complex was maximized at a potassium ion concentration of 100 mM. Stimulation of kinase activity was also found with rubidium ion but not with lithium and sodium ions. All salts tested increased the efficiency of inactivation by phosphorylation, i.e., decreased the degree of enzyme phosphorylation required to cause inactivation of the complex. The effectiveness and efficacy of alpha-chloroisocaproate as an inhibitor of branched-chain alpha-ketoacid dehydrogenase kinase were enhanced by the presence of monovalent cations, and further increased by inorganic phosphate. These findings suggest that monovalent cations and anions, particularly potassium and phosphate, cause structural changes in the dehydrogenase-kinase complex that alter its susceptibility to phosphorylation and responsiveness to kinase inhibitors.

Animals↗

The high pH therapy for cancer tests on mice and humans.

Mass spectrographic and isotope studies have shown that potassium, rubidium, and especially cesium are most efficiently taken up by cancer cells. This uptake was enhanced by Vitamins A and C as well as salts of zinc and selenium. The quantity of cesium taken up was sufficient to raise the cell to the 8 pH range. Where cell mitosis ceases and the life of the cell is short. Tests on mice fed cesium and rubidium showed marked shrinkage in the tumor masses within 2 weeks. In addition, the mice showed none of the side effects of cancer. Tests have been carried out on over 30 humans. In each case the tumor masses disappeared. Also all pains and effects associated with cancer disappeared within 12 to 36 hr; the more chemotherapy and morphine the patient had taken, the longer the withdrawal period. Studies of the food intake in areas where the incidences of cancer are very low showed that it met the requirements for the high pH therapy.

Animals↗

Neuropsychiatric manifestations of alkali metal deficiency and excess.

The alkali metals from the Group IA of the periodic table (lithium, sodium, potassium, rubidium, cesium and francium) are reviewed. The neuropsychiatric aspects of alkali metal deficiencies and excesses (intoxications) are described. Emphasis was placed on lithium due to its clinical uses. The signs and symptoms of these conditions are characterized by features of an organic brain syndrome with delirium and encephalopathy prevailing. There are no clinically distinctive features that could be reliably used for diagnoses. Sodium and potassium are two essential alkali metals in man. Lithium is used as therapeutic agent in bipolar affective disorders. Rubidium has been investigated for its antidepressant effect in a group of psychiatric disorders. Cesium is under laboratory investigation for its role in carcinogenesis and in depressive illness. Very little is known of francium due to its great instability for experimental study.

Cesium↗

Mechanism of lithium action: in vivo and in vitro effects of alkali metals on brain superoxide dismutase.

Intraperitoneal administration of lithium (2 mEq/kg/day) was found to increase the superoxide dismutase (SOD) activity in certain brain regions after 24 hours (2 injections) and 3 days (once a day) of exposure. In vitro addition of wide range of lithium (0.1 to 8 mEq) to enzyme preparation as well activated cortical SOD activity; however, at 10 mEq concentrations an inhibition was observed. The increase in SOD activity did not appear to be region specific as under both in vivo and in vitro conditions lithium enhanced enzyme activity in all the tested brain regions. The effects of intraperitoneal administration of 2 mEq/kg rubidium and cesium for 24 hr (2 injections) and 6 days (once a day) were also studied on central SOD. Both the alkali metals were not found to produce any significant alteration in the cortical enzymic activity. When the in vitro effects of these monovalent alkali metals were tested, only 2 mEq rubidium was found to increase cortical SOD; however, cesium and potassium at similar concentration did not produce any appreciable effects. It appears from the data that lithium-induced increase in brain SOD activity is not an unspecific effect of alkali metals. SOD enzyme disposes cytotoxic superoxide radicals which, if not removed, could impair the normal functioning of cellular membrane and produce a variety of psychedelic compounds as well. The activation of central SOD by lithium would enhance the disposal process of superoxide radicals whose pathological concentrations may be present in affective disorders. The mechanism of lithium-induced activation of SOD, at present, is not known.

Animals↗

Sarcolemmal and mitochondrial effects of a KATP opener, P-1075, in "polarized" and "depolarized" Langendorff-perfused rat hearts.

We investigated consequences of cardiac arrest on sarcolemmal and mitochondrial effects of ATP-sensitive potassium channel (KATP) opener, P-1075, in Langendorff-perfused rat hearts. Depolarised cardiac arrest (24.7 mM KCl) did not affect glibenclamide-sensitive twofold activation of rubidium efflux by P-1075 (5 microM) from rubidium-loaded hearts, but eliminated uncoupling produced by P-1075 in beating hearts: 40% depletion of phosphocreatine and ATP, 50% increase in oxygen consumption, and reduction of cytochrome c oxidase. Depolarized cardiac arrest by calcium channel blocker, verapamil (5 microM), also prevented uncoupling. Lack of P-1075 mitochondrial effects in depolarized hearts was not due to changes in phosphorylation potential, because 2,4-dintrophenol (10 microM) reversed the [PCr]/[Cr] increase and Pi decrease, characteristic of KCl-arrest, but did not restore uncoupling. In agreement with this conclusion, pyruvate (5 mM) increased [PCr]/[Cr] and decreased Pi, but did not prevent uncoupling in beating hearts. A decrease in mean [Ca2+] in KCl-arrested hearts could not account for lack of P-1075 mitochondrial effects, because calcium channel opener, S-(-)-Bay K8644 (50 nM), and beta-agonist, isoproterenol (0.5 microM), did not facilitate uncoupling. In contrast, in adenosine (1 mM)-arrested hearts (polarized arrest), P-1075 caused 40% phosphocreatine and ATP depletion. In isolated rat liver mitochondria, P-1075 (20 microM) decreased mitochondrial membrane potential (DeltaPsi) by approximately 14 mV (demonstrated by redistribution of DeltaPsi-sensitive dye, rhodamine 800) in a glibenclamide-sensitive manner. We concluded that cell membrane depolarization does not prevent activation of sarcolemmal KATP by P-1075, but it plays a role in mitochondrial uncoupling effects of P-1075.

Animals↗

The mechanism of ion conduction by valinomycin: analysis of charge pulse responses.

Even though valinomycin has been employed and studied extensively for over 30 years, the attempts to explain its mechanism have not been entirely successful. The basic carrier model uses four rate constants that describe association of an ion and carrier, transfer of the complex across the membrane, dissociation of the complex, and transfer of the free carrier back across the membrane. If the basic model is correct all of these constants are independent of ion concentration. In previous work with rubidium the rate constants for transfer of free carrier, transfer of complexes, and dissociation were independent of the concentration, but the rate constant for association varied markedly. No satisfactory explanation for these observations was proposed. In this study current relaxations after charge pulses have been analyzed using digital data acquisition, a Bayesian algorithm, and inspection of linear plots of residuals. In agreement with previous results the relaxations for sufficiently high rubidium or potassium concentrations contain three exponential components, but the rate constants for association and dissociation decrease to similar extents as ion concentration increases. A simple extension of the carrier model to allow a more realistic description of association and dissociation is in good agreement with the rate constants fitted in the present study but not those for low ion concentrations found in previous work. At high ion concentrations the rate-limiting step in association appears to be a change in the conformation of the free carrier preceding the bimolecular association reaction. Transfer of neutral, free valinomycin between the surfaces is slower than the transfer of the charged ion-valinomycin complexes. Transfer of the complex may be hastened by deformation of the membrane, or transfer of the free carrier may be slowed by a need for conformation changes.

Algorithms↗

Synthesis, characterisation, thermal and explosive properties of 4,6-dinitrobenzofuroxan salts.

Two new initiatory molecules, e.g. rubidium and cesium salts of 4,6-dinitrobenzofuroxan (DNBF) have been prepared by reacting sodium salt of 4,6-dinitrobenzofuroxan (DNBF) with rubidium nitrate and cesium nitrate, respectively, at 60 degrees C in aqueous medium. The characterisation of compounds by IR, (1)H-NMR, elemental analysis and metal content is described along with some of the evaluated thermal and explosive properties. The results indicate that cesium salt of DNBF (Cs-DNBF) appears promising initiatory and may suitably replace potassium salt of DNBF (K-DNBF), being used currently in initiatory compositions.

Cesium↗

Monovalent cations differ in their effects on transcription initiation from a sigma-70 promoter of Escherichia coli.

Initiation of transcription from the sigma-70 rep promoter of plasmid pBR322 was measured by abortive transcription assays at various concentrations of potassium, rubidium, and sodium acetate. When linear and negatively supercoiled templates were compared, each salt generated a characteristic response. Increasing the salt concentration decreased transcription from a linear template but produced an increase (potassium) or a bell-shaped response (rubidium) with a supercoiled template. In the case of sodium ions, increasing concentration inhibited transcription initiation from both linear and supercoiled templates. These results are discussed with respect to effects of monovalent cations on DNA twist.

Base Sequence↗

Rb+ and Na+ spin relaxation in aqueous gellan solutions and implication of selective site binding of alkali metal ions.

87Rb NMR was applied to investigate the site binding of Rb+ ions in gellan gum gels. The temperature dependence of the transverse and longitudinal relaxation NMR relaxation rates of 87Rb+ ion and 23Na+ ion have been compared in aqueous 5% (w/v) rubidium-type and sodium-type gellan. In each sample, the relaxation rates were sensitive to the conformation (helix or random coil). In rubidium-type gellan, significant line-broadening effects (losses in intensity) were found, which is due to the presence of cation-binding sites in the ordered conformation. In sodium-type gellan, such an enhancement of the relaxation was not observed. These results indicated that gellan gum produced highly selective binding sites for alkali metal ions, in which Rb+ ion bound more strongly than Na+ ion. The 87Rb NMR line shift suggested selective site binding of ions to form the cross-linking domains in gellan gels.

Binding Sites↗

Structure of anhydrous alkali-metal formates.

Single-crystal X-ray diffraction has yielded new crystal structures for cesium formate (CsOOCH) and rubidium formate (RbOOCH). The cesium formate structure has the same unit cell and space group as that published from powder X-ray diffraction data but differs radically in the placement and orientation of the formate ions. The new crystal structure has been successfully modeled with an empirical force field based on pair potentials, whereas it proved impossible to develop a force field that gave an adequate description of the powder structure. For rubidium formate, the gross structure is similar to that previously published, but the space group includes a mirror plane (Pbcm rather than Pbc2(1)). From this information, we have been able to analyze the effect of the cation size on the crystal structure for alkali-metal formates.

Cesium↗

Cation transport abnormalities in vivo in untreated essential hypertension.

In order to study cation transport in vivo we have measured the changes in plasma and intra-erythrocytic rubidium concentrations after the oral administration of rubidium chloride. In this paper we describe our findings in 22 patients with untreated essential hypertension, compared with the findings in 22 carefully matched control subjects. Our findings in patients receiving short-term digoxin therapy and in patients with chronic renal failure are also included for comparison. Whereas the findings in patients receiving digoxin and in patients with chronic renal failure are compatible with a widespread reduction in sodium, potassium-ATPase activity in vivo, the findings in patients with untreated essential hypertension are not. Further analysis of the data and a similar study of the disposition of 42K after the intravenous administration of 42KCl suggest that in vivo net cation transport is enhanced in the erythrocytes of patients with untreated essential hypertension.

Adult↗