Affect Sodium Transport Research Articles

Effect of epidermal growth factor on sodium transport in the cortical collecting tubule.

Receptors for epidermal growth factor (EGF) have been demonstrated in the distal tubule. To determine whether there are acute functional correlates, we studied the effect of EGF on cortical collecting tubule (CCT) transepithelial voltage and transport of sodium and bicarbonate. Rabbit CCT were perfused in vitro and EGF was added to either the bathing medium or the luminal perfusate after base-line measurements of transport. Peritubular EGF in concentrations of 0.1 to 100 ng/ml (1.7 X 10(-11) to 1.7 X 10(-8) M) decreased sodium reabsorption, measured as 22Na absorption from the lumen, by 44-59%. There was a corresponding fall in the lumen-negative transepithelial voltage. Lower doses of EGF were without effect on transepithelial voltage or sodium transport. Pretreatment of the tubules with ouabain eliminated the effect of EGF on sodium transport. In contrast to peritubular EGF, luminal EGF (100 ng/ml) did not affect sodium transport. Peritubular EGF had no effect on either bicarbonate secretion or net bicarbonate transport in the CCT and no effect on net bicarbonate reabsorption in the medullary collecting tubule. Using the pH sensitive, fluorescent dye 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, no change in principal cell intracellular pH was found after peritubular EGF. Two other growth factors, insulin and insulin-like growth factor I were without effect on sodium transport. We conclude that EGF inhibits active sodium absorption in CCT via receptors located at the basolateral membrane.

Aldosterone in colonic potassium adaptation in rats.

The influence of adrenalectomy and administration of aldosterone on potassium secretion by colonic epithelium was studied in vivo in rats, particularly in relation to potassium adaptation (induced by feeding a potassium-rich diet) and the response to acute i.v. administration of a potassium load. Adrenalectomy (rats maintained on dexamethasone and saline) impaired the development of potassium adaptation or considerably reduced it if the rats had been previously adapted. The partial adaptation observed in the adrenalectomized rats may be related to the increased plasma potassium concentration developed when these rats received the potassium-rich diet. Within 2 h of acute aldosterone administration, the response of the potassium secretion rate to acute potassium loading in adrenalectomized rats was significantly improved. When aldosterone (2 micrograms/day per 100 g body weight, given by osmotic minipump) was added to the replacement treatment, the plasma concentration of potassium was similar to that of the intact rats, and both potassium adaptation and the response to the acute potassium load were completely restored. Transepithelial potential difference and sodium transport were not stimulated, being similar to the values in intact rats. Considerable changes in potassium secretion induced by acute potassium loading did not significantly affect sodium transport. The findings suggest that the sodium and potassium epithelial pathways are, to a large extent, independently influenced by aldosterone. Aldosterone appears to be essential for complete adaptation and, in a relatively low dose, can completely restore potassium adaptation and the response to acute potassium loads in adrenalectomized rats.

Lipid methylation, sodium transport and the response to PTH in renal tubules

The possible role of progressive methylation of phosphatidylethanolamine to phosphatidylcholine on sodium transport was examined in a suspension of rabbit proximal convoluted tubules. The relation between progressive methylation and the action of parathyroid hormone on sodium transport in this nephron segment was also determined. Incubation of the suspended tubules for 10 minutes at 37°C with 200 uM S-adenosyl-L-[3H]-methyl methionine, a methyl donor, revealed a significant rate of de-novo phosphatidylcholine synthesis. The inactive adenosine analogue, 3-deazaadenosine (DZA), had a significant inhibitory effect on lipid methylation. Despite the inhibition of methylation by DZA, the ouabain sensitive component of oxygen consumption, an index of sodium transport, was not affected. PTH significantly inhibited ouabain sensitive oxygen consumption but had no effect on the methylation of phosphatidylethanolamine. Inhibition of methylation by DZA, did not affect the inhibitory effect of PTH on oxygen consumption. These studies demonstrate that in the proximal convoluted tubule of the rabbit the progressive methylation pathway is present and that inhibition of this pathway does not affect sodium transport. In addition, these studies suggest that the inhibitory effect of PTH on sodium transport is not mediated by the methylation pathway.

Effects of standard diuretics and RPH 2823 on transepithelial Na+ transport in isolated frog skin

Short-circuit current (SCC) techniques were used to monitor the effects of various diuretic agents on Na+ transport in isolated frog skin, a model for the late distal tubule and the collecting duct of the mammalian kidney. Acetazolamide, hydrochlorothiazide, torasemide, and ethacrynic acid did not affect sodium transport (as indicated by the SCC) or transepithelial electrical resistance when added either to the apical (outer) or to the inner (basolateral, corial) bathing solution of the tissue. However, Na+ transport was sensitive to amiloride, the triamterene derivate dimethylamino-hydroxypropoxytriamterene (RPH 2823), and to furosemide. Whereas apical amiloride, and RPH 2823 induced a dose-dependent decrease in SCC and increase in transepithelial electrical resistance, apical furosemide resulted in a dose-dependent increase in SCC and a decrease in electrical resistance. None of the three diuretic agents caused a significant change in SCC when applied to the inner bathing Ringer's solution. The small furosemide-induced decrease in resistance compared with the huge increase in SCC suggests that furosemide affects Cl- permeability as well as Na+ permeability. Evidence for this notion was achieved by the following findings: The decrease in resistance after furosemide was more pronounced in tissues bathed in Cl(-)-free solutions compared with Cl(-)-containing solutions. n contrast, SCC stimulation by apical furosemide is Cl(-)-ion independent, but strongly Na+-ion dependent. SCC stimulation by furosemide is amiloride-sensitive. With respect to the onset, locus, and reversibility of action, it seems reasonable to assume that amiloride, RPH 2823, and furosemide all influence transepithelial Na+ transport by interacting with the Na+ channel or a regulator site of it within the apical membrane. The stoichiometry of the amiloride (RPH 2823)-receptor site interaction revealed Hill-coefficient(s) of less than 1, indicating a negative cooperativity among the receptor sites. The interaction between Na+ ions and amiloride or RPH 2823 displayed mixed competitive-noncompetitive inhibition. Taken together, these results support the hypothesis that amiloride and Na+ as well as RPH 2823 and Na+ may act at different loci on the apical entry mechanism in Rana esculenta skin.

Guanabenz: A centrally acting, natriuretic antihypertensive drug

Guanabenz is acutely natriuretic and diuretic in saline expanded animals. In man, guanabenz has not resulted in sodium retention as seen with other comparable antihypertensives. To directly define the action of guanabenz on sodium and water excretion in man, we performed clearance studies during water diuresis on eight hypertensive subjects under metabolic balance conditions. Each subject underwent three studies: 1) baseline study: no drug, a water diuresis study; this was followed by a saline load (= 2% BW); 2) acute study (24 hr after baseline): 16 mg guanabenz PO; and 3) chronic study: after one week of guanabenz 8 mg PO BID. In the acute guanabenz studies there were: 1) no changes in GFR or ERPF; 2) an increase in both sodium excretion and fractional sodium excretion; 3) a rise in free H2O clearance (CH2O) and (CH2O/GFR) X 100%. These findings were not sustained in the chronic guanabenz studies. We conclude that in man (preconditioned with prior saline loading) guanabenz is acutely natriuretic and water diuretic. These effects are due to decreased tubular sodium and water reabsorption, probably related to inhibition of alpha adrenergic activity. The data are consistent with selectively reduced renal sympathetic activity affecting sodium transport and provide a basis for the absence of edema and sodium retention associated with guanabenz therapy.

Unidirectional sodium fluxes in red beet storage tissue (Beta vulgaris L. cv. Platronde Egyptische): effects of the phytohormones indol‐3yl‐acetic acid and abscisic acid

Abstract. The influence of indol‐3yl‐acetic acid (IAA) and abscisic acid (ABA) on the capacities of the cytoplasm and vacuole and their effects on unidirectional sodium fluxes across the plasmalemma and the tonoplast of aged red beet storage tissue was investigated. After loading the tissue in a labelled NaCl solution the efflux of radio‐activity was measured in unlabelled NaCl. By means of compartmental analysis the capacities and fluxes were determined and compared with those obtained after loading and elution in the presence of IAA or ABA.It was established that both IAA and ABA affect sodium transport across the principal cell membranes. Both hormones inhibited the efflux across the plasma‐lemma, possibly by affecting a Na+ for H+ exchanging system. Efflux across the tonoplast was stimulated by IAA and influx across the same membrane was enhanced by ABA. It was suggested that IAA stimulated a proton pump at this level while the influence of ABA remained difficult to explain.

Is a circulating sodium transport inhibitor involved in the pathogenesis of essential hypertension?

There is controversy about the relationship between sodium intake and the prevalence of high blood pressure. Part of this controversy relates to how an increase in sodium intake could cause an increase in peripheral resistance. We have put forward the following hypothesis. In essential hypertension there is an inherited defect of the kidney's ability to excrete sodium which becomes increasingly obvious the greater the sodium intake. This difficulty in sodium excretion by the kidney increases the concentration of a circulating sodium transport inhibitor that affects sodium transport across many cell membranes. In the kidney the inhibitor adjusts urinary sodium excretion back towards normal so that sodium balance is near that of normal subjects on the same intake of sodium. In the arteriolar smooth muscle the inhibition of sodium transport across the cell wall causes a rise in intracellular sodium concentration which, in turn, raises the intracellular calcium concentration and thus increases vascular reactivity. This hypothesis also proposes that the abnormalities of sodium transport in circulating cells in vivo are directly due to the increased secretion of the circulating sodium transport inhibitor. Evidence supporting this hypothesis is discussed. Firstly, it is pointed out that there is much evidence which suggests that there is a circulating inhibitor of Na+-K+-ATPase, the level of which is related to sodium intake and that the level of this inhibitor appears to be increased in many hypertensives. Secondly, the finding that normotensive white cells incubated in the plasma of hypertensive patients develop the same decrease in the Na+-K+-ATPase dependent sodium transport as the hypertensives own white cells also suggests that hypertensives have an increase in a circulating Na+-K+-ATPase inhibitor.

Inhibition of sodium transport by prostaglandin E2 across the isolated, perfused rabbit collecting tubule.

This study was designed to examine whether prostaglandin E2 can directly affect sodium transport across isolated perfused rabbit renal collecting tubules. Changes in transepithelial potential and isotopic sodium fluxes in response to peritubular prostaglandin E2 were measured. In addition, changes in transepithelial potential of the outer medullary collecting tubule in response to prostaglandin E2 were also measured. With few exceptions, all rabbits received 5 mg/day desoxycorticosterone acetate for 4-11 days before experimentation. The results of the experiments show that: (a) prostaglandin E2 inhibits the negative transepithelial potential in the cortical collecting tubule as well as the outer medullary collecting tubule; (b) prostaglandin E2 inhibits net sodium transport out of the lumen by inhibiting efflux while backflux is unaffected; (c) prostaglandin E2 produces this inhibition within 15 min, and the effects are dose dependent and reversible. These results suggest that prostaglandin E2 may modulate sodium transport in vivo and may contribute to the final regulation of sodium excretion.

A factor in pre-eclamptic serum affecting sodium transport across a membrane.

SummaryThe serum from non‐pregnant and normotensive pregnant women and from women with pre‐eclampsia tested for its effect on the rate of sodium transport across a frogskin membrane. There is a factor in pre‐eclamptic serum which alters the rate of sodium transport.

The effect of metal ions and antidiuretic hormone on oxygen consumption in toad bladder.

1. The sodium-dependent oxygen consumption of pieces of toad bladder (Bufo marinus) has been investigated using an oxygen electrode.2. The effect of polyvalent cations (Ca(2+), Sr(2+), Mg(2+), Eu(3+), La(3+) and Mn(2+)) on sodium-dependent oxygen consumption has been measured. All cations inhibited oxygen consumption, the order of effectiveness being Ca(2+) > Sr(2+) > Mg(2+) > Mn(2+) > Eu(3+) > La(3+).3. Treatment of bladder pieces with antidiuretic hormone (50 m-u./ml.) decreased the effectiveness of Ca(2+) and Sr(2+) as inhibitors of sodium-dependent oxygen consumption. Mn(2+), Eu(2+) and La(2+) were more effective after hormonal treatment, while the effectiveness of Mg(2+) was unaltered.4. The results have been interpreted in terms of a model in which sodium entry to the transporting mechanisms of the epithelium is controlled by Ca(2+), and in which antidiuretic hormone alters Ca(2+) binding and so affects sodium transport.

Salt transport across isolated frog skin.

We have measured on isolated epithelia of Rana skin the amount of tissue sodium that equilibrates with the sodium present in the solution in contact with the outside surface. Only about 12 % of the sodium in the tissue equilibrated with outside sodium. Antidiuretic hormone (0.1 u/ml) and ouabain (10 -4 mol l -1 ) had no effect on the amount of cell sodium that equilibrated with outside sodium. We have also studied with the electron microscope the localization of the permeability barriers of frog skin epithelium using as tracers ruthenium red and colloidal and ionic lanthanum. Our observations indicate that there are two barriers to diffusion in frog skin epithelium. The first is at the s. corneum, the second at the s. granulosum. Of these, the first is the least selective. In other experiments the effects of acetazolamide and amiloride on active transport of both sodium and chloride were determined. Acetazolamide (10 -4 mol l -1 ) blocked chloride transport without affecting sodium transport. Amiloride (10-4 mol l-1) blocked sodium transport and did not modify chloride transport. These results and others available in the literature are used to raise some defined questions on the relationship between structure and function and the coupling of ion fluxes in frog skin.

The effects of anions on sodium transport.

1. Substitution of chloride by isethionate reduces the short circuit current (SCC) and increases the potential of isolated frog skin. In sodium isethionate Ringer antidiuretic hormone and choline chloride increase the SCC, whereas theophylline is ineffective.2. Frog skins treated on the outside with copper ions always show an increased potential when bathed in normal Ringer solution. The SCC may be moderately increased or decreased.3. Theophylline increases skin thickness and cell volume in non-short-circuited skins.4. The ways in which the theophylline-induced increase in chloride permeability affects sodium transport is discussed, together with the requirements for a permeant anion in both short- and open-circuited skins.

Failure of tetrodotoxin to affect sodium transport by frog skin and proximal tubule of rat kidney

Failure of tetrodotoxin to affect sodium transport by frog skin and proximal tubule of rat kidney

The effect of aldosterone on glucose metabolism in toad bladder.

Adolesterone has been shown to reduce 14CO2 release from [1-14C]glucose in the urinary bladder of the toad in vitro. This effect occurs at a time when 14CO2 released from [6-14C]glucose is enhanced, as is the metabolism of the tissue. However, in the absence of sodium, which abolishes the hormonal stimulation of metabolism, the effect of aldosterone to decrease 14CO2 from [1-14C]glucose is still demonstrable. The effects on glucose metabolism and on sodium transport appear to have the same time course of onset and dependence on the concentration of the hormone. Like the effect on sodium transport, it is abolished by actinomycin D at a concentration of 1.4·10−6 M. Dexamethasone and deoxycorticosterone (5·10−7 M) like aldosterone, stimulate sodium transport and decrease the 14CO2 from [1-14C]glucose whereas progesterone (5·10−7 M) fails to affect sodium transport and has no effect on glucose metabolism in this tissue. It is concluded, therefore, that this effect could stand in a cuasal relation to stimulation of sodium transport or that both could result from a common precursor affected by the hormone in the tissue. A third possibility is that this effect is an independent glucocorticoid effect of aldosterone. However, this would require that the similarities between the stimulation of sodium transport and the effect on glucose metabolism be coincidental.