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Biomedical subjects

A Z Györy

Publications and source records attributed to A Z Györy.

At least 19 recordsLinked to original sources

Tubular sodium handling and tubuloglomerular feedback in compensatory renal hypertrophy.

Tubular sodium handling and tubuloglomerular feedback (TGF) activity were assessed in established compensatory renal hypertrophy in Sprague Dawley rats. Hyperfiltration at the level of the single nephron was confirmed 4-6 weeks following a reduction in renal mass. TGF activity, determined as the difference between late proximal and early distal measurements of single-nephron glomerular filtration rate (SNGFR), was significantly increased in compensatory renal hypertrophy, being 7.8 +/- 1.0 vs 23.3 +/- 1.9 vs 25.5 +/- 2.6 nl/min (P for analysis of variance less than 0.05) following sham operation, unilateral nephrectomy, and 1 1/3 nephrectomy, respectively. Enhanced net tubular Na transport was also observed, with total Na reabsorption up to the late proximal site being 1.8 +/- 0.2 vs 2.7 +/- 0.1 vs 3.1 +/- 0.3 nmol/min (P less than 0.05), and to the early distal site being 3.4 +/- 0.5 vs 5.8 +/- 0.6 vs 7.9 +/- 0.8 nmol/min (P less than 0.05) in the three animal groups respectively. Comparison of proximal tubular length demonstrated a 71.9 +/- 8.1% increase in uninephrectomised vs sham-operated animals. This increase was proportionately greater than the increase in proximal Na reabsorption (50.0 +/- 4.0%) observed in the corresponding animal groups. Concurrent electron microprobe experiments in uninephrectomised and sham-operated animals demonstrated that the proximal tubular intracellular Na concentration was significantly lower following uninephrectomy (16.8 +/- 0.6 vs 18.9 +/- 0.5 mmol/kg wet weight, P less than 0.01), in association with evidence of reduced basolateral Na/K-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Electron probe X-ray microanalysis of intracellular element concentrations in cryosections in the presence of changes in cell volume.

The interpretation of element concentration data for X-ray microanalyses of biological tissues, which are subjected to some experimental treatment, can be complicated by changes in cell volume and total cell dry matter induced by the treatment. We have examined the manner in which such changes would affect the values measured in frozen-dried cryosections of soft tissues, and how they may be taken into account in the interpretation of the results. The element content (mass per unit dry weight) measured by the peak-to-continuum or Hall method is independent of changes in cell volume, but is sensitive to a change in the local dry mass. Conversely, intracellular concentrations in terms of mass per unit volume, as determined by the peripheral or internal standard technique, are dependent on volume changes but independent of dry mass. The estimated dry weight fraction is affected by changes in both volume and dry mass. The results obtained from both quantification methods can therefore provide information on the combination of changes in cellular element levels, volume and total dry mass that may occur following the experimental treatment. In a study of the late effect of the drug cisplatin on electrolyte concentrations in kidney proximal tubules, both quantification methods have been used to obtain wet weight and dry weight concentrations. By applying the above considerations, the analytical results have been interpreted as a combination of changes in element levels and a shrinkage of the tubule cells. Cell shrinkage was confirmed by morphometric analysis of tubular cross-sections.

Animals

Transfer of Na transport inhibition in proximal tubules from saline volume-expanded to nonexpanded rats.

In dual micropuncture experiments the shrinking drop technique was used to measure volume flux with artificial tubular fluid (AF) alternating with harvested tubular fluid (HTF) during saline volume-expanded (VE) and nonexpanded (NE) periods. In VE rats, volume flux (Jv) (nl.mm-1.min-1) with AF was 1.78 +/- 0.08 (means +/- SE) during NE and was reduced to 1.39 +/- 0.09 (P = 0.01) during subsequent VE, whereas with randomly alternating HTF during VE it was 1.07 +/- 0.08 (P less than 0.0001 and less than 0.03, respectively). Jv with HTF from NE rats tested in the VE rats was 1.20 +/- 0.06, which is significantly higher than that measured with their own HTF (Wilcoxon rank, P = 0.05). In NE rats Jv was 1.65 +/- 0.10 and 1.69 +/- 0.10 with AF and HTF and was 1.28 +/- 0.07 (P less than 0.001 from both) with HTF obtained from VE rats. Elemental analysis of reaspirated tubular fluids showed no significant differences in Na or Cl concentrations among any of the fluids. It is concluded that during VE, a transferable Na transport inhibitor appears in proximal tubular fluid, which, together with a changed proximal tubular epithelium, possibly due to physical forces, accounts for proximal tubular Na transport inhibition during VE.

Animals

Differential effects of angiotensin II and noradrenaline on tubular rejection of sodium produced by ANP in rats.

The effect of Atrial Natriuretic Peptide (ANP) on renal tubular sodium handling (FENa) in the presence of converting enzyme inhibition (CEI), the AII antagonist Saralasin (SAR), noradrenaline (NA) and angiotensin II (AII) infusions was investigated. FENa and increases in FENa produced by ANP were significantly lower with CEI (p less than 0.03 and 0.0001) or SAR (p less than 0.02 and 0.02) against control (Vehicle + ANP). Mean arterial pressures (MAP) were also reduced. Returning MAP to 107 +/- 2 mmHg with NA (+CEI+ANP), did not change FENa (1.22% +/- 0.16 to 1.25% +/- 0.18, p greater than 0.66) whereas without CEI but with ANP (MAP 113 +/- 2 mmHg) FENa was significantly increased by NA (2.34% +/- 0.36, p less than 0.02). With AII+CEI+ANP, MAP was restored to 110 +/- 5 mmHg, and FENa was highly significantly increased (0.99% +/- 0.20 to 3.04% +/- 0.39, p less than 0.0003) in excess of that expected due to pressure effects alone. It is concluded the additional effect of AII on FENa (3.04 versus 1.25% with NA) at equivalent perfusion pressures are due to a separate additive phenomenon of AII and ANP both causing tubular rejection of Na.

Angiotensin II

Acute mannitol and saline volume expansion in the rat: effect on transepithelial potential difference in proximal tubules.

1. Transepithelial potential difference (PDte) of proximal tubules was measured in rats under control conditions (C), and mannitol-saline and saline extracellular fluid volume expansion (MVE, SVE, respectively) under conditions of normal net lumen to basal sodium transport. 2. PDte was measured in kidneys bathed with Hartmann's solution or covered with mineral oil under both volume-expanded conditions together with their controls. 3. PDte was significantly lower in kidneys bathed with Hartmann's solution than those covered with oil. 4. In MVE rats, with mineral oil covering the kidneys, PDte (expressed as mean and s.e.m.) was for the control 2.20 +/- 0.05 (n = 45) mV and MVE 1.97 +/- 0.04 (n = 36) mV, lumen positive, a significant reduction of 10% (P less than 0.001). In SVE rats, with mineral oil covering the kidneys, PDte was for C = 2.42 +/- 0.05 (n = 74) mV and SVE = 1.93 +/- 0.03 (n = 67) mV, a significant reduction (P less than 0.001) of 20%. 5. According to thermodynamic considerations, neither of these changes is sufficient to explain the 50% inhibition of Na transport measured previously during MVE and SVE with autologous tubular fluid. The present results offer further evidence supporting the idea that the inhibition of Na transport during MVE and SVE is largely due to inhibition of the active Na transporting step.

Animals

Urine microscopy.

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Australia

Randomised comparison of methyldopa and oxprenolol for treatment of hypertension in pregnancy.

Fifty-three pregnant women with moderately severe hypertension were randomly allocated to treatment with methyldopa or oxprenolol. There were no significant differences between the groups in age, height, weight, parity, or stage of gestation at the start of treatment. The outcome of pregnancy was better in the group treated with oxprenolol, with greater maternal plasma volume expansion and placental and fetal growth. No intrauterine deaths occurred in either group, and antepartum fetal distress, detected by oxytocin challenge testing, was evident in only one patient, who received methyldopa. This infant, and one other in the methyldopa group, died in the neonatal period. No neonatal deaths occurred in the oxprenolol-treated group. Even in this small number of patients these results were considerably better than those in untreated women with hypertension of similar severity. Apgar scores in both groups were equivalent at birth, while blood sugar concentrations were higher in the oxprenolol group. Oxprenolol appears to be safe and effective in controlling hypertension during pregnancy. There was no evidence of harmful effects on the fetus, and oxprenolol may offer a selective advantage over methyldopa for fetal growth and wellbeing in utero.

Adult

Cryoactivation of renin in plasma from pregnant and nonpregnant subjects, and its control.

Plasma renin activity increased by a mean of 7% from baseline values when blood from nonpregnant persons was kept at 0 degrees C for 5 h before incubation. Freezing chilled plasma and thawing it before incubation resulted in a mean increase of 11%. The same procedures used on plasma from normal pregnant women produced mean increases in plasma renin activity of 44 and 89%, respectively. If blood from pregnant women was kept at 0 degrees C for 5 h, and the plasma then separated, frozen, and thawed before incubation, the resulting mean increase in plasma renin activity from baseline values was 160%. We conclude that plasma from pregnant women should be handled at room temperature, or, if samples must be stored, they must be rapidly frozen, then thawed as rapidly as possible before incubation and assay if results are to be reproducible.

Enzyme Activation

Plasma volume contraction: a significant factor in both pregnancy-associated hypertension (pre-eclampsia) and chronic hypertension in pregnancy.

The role of plasma volume in hypertension in pregnancy (pre-eclampsia) was investigated. Significant volume expansion from non-pregnant levels (16.5 +/- 1.60 ml/cm height) was present throughout pregnancy in 189 normal women, reaching 23.1 +/- 1.21 ml/cm at 33-36 weeks amenorrhoea. In another 40 initially normotensive pregnant women who developed hypertension, similar early volume expansion was followed by significant volume contraction in the third trimester, before evaluation of blood pressure in 29 (20.6 +/- 1.26 ml/cm), after it in 11 (18.6 +/- 1.27 ml/cm). Equivalent volume contraction was present in another 44 women studied only after hypertension developed in the third trimester. Oedema had no value as a clinical sign. In another 30 women with chronic hypertension, blood pressure was inversely related to plasma volume (r = 0.822) and to fetal growth (r = -0.710), which was directly related to plasma volume (r = 0.701). Plasma volume depletion plays a significant role in hypertension in pregnancy.

Blood Pressure

Improvement in foetal growth with treatment of maternal hypertension in pregnancy.

1. A highly significant inverse relationship was found between blood pressure in untreated hypertensive subjects in late pregnancy and birth weight. 2. Reversal of this intrauterine growth retardation was achieved in 19 patients by treatment of hypertension with oxprenolol. 3. No adverse effects from oxprenolol were found in the patients or in their babies.

Birth Weight

Immunoglobulin deposition in the kidney in pre-eclampsia: its significance.

Renal biopsies from two patients with classical toxaemia of pregnancy demonstrated heavy deposition of IgG and IgA in a predominantly finely granular pattern. It is suggested that this may be a manifestation of immune complex formation and may provide further evidence for an immunological basis for the renal lesion of this poorly understood disease process.

Adult

Studies on the binding characteristics of antimycin A and albumin in relation to the inhibitor activity of the complex on rat proximal tubular sodium transport.

As reported previously [11] Antimycin A is effective in inhibiting sodium transport of the proximal tubule only when applied to the luminal side and in the presence of albumin. Therefore the interaction of Antimycin A with albumin was examined with the technique of equilibrium dialysis. It was found that Antimycin A was bound to albumin at five sites with a dissociation constant of 2.5 X 10(-6) M. This finding suggests that Antimycin A is taken up by the tubular cell as an Antimycin A/albumin complex via pinocytosis. In the pinocytotic vesicle this complex probably dissociates, and free Antimycin A is released into the cytoplasm where it can reach it's sites of action in the mitochondria and at the plasma membrane. This uptake mechanism might provide a general method to incorporate substances into the cell which do not penetrate the plasma membrane.

Antimycin A

Predicting the development of pregnancy-associated hypertension. The place of standardised blood-pressure measurement.

82 initially normotensive pregnant women with no known history of renal disease were seen at monthly intervals from 16 weeks' amenorrhoea onwards, and their blood-pressure (B.P.) was measured sitting and lying on their left side. 15 developed hypertension (B.P. greater than 135/85 mm Hg lying on the left side) in late pregnancy. When these women were compared with the 67 who remained normotensive throughout, their B.P.s were found to be significantly higher even in early pregnancy, although individual patients were not always separable in this way. When B.P. measured in this rigidly standardised manner was compared with routine antenatal clinic values, it was apparent that the latter did not detect the difference between the two groups. Women who develop hypertension in the third trimester of pregnancy (pre-eclampsia) may represent a separate group from entirely normal pregnant women from the beginning of pregnancy.

Adolescent

Trans-proximal tubular steady-state concentration differences studied by micro-puncture and tissue content of sodium and chloride at varying intraluminal sodium concentrations in vitro in rat kidney cortex slices: evidence for a multisite sodium transport system.

1. With the aid of micropuncture techniques, proximal tubular transepithelial concentration differences for Na (deltaC Na) and chloride (deltaC Cl) were measured in kidney cortex slices at bathing fluid Na concentrations from 10 to 400 m-mole. kg-1. Tissue content of water, Na and K was also measured in such slices. Under steady-state conditions of zero net flux of NaCl and water, deltaC Na represents the sum of active Na transport, factored by the tubular permeability coefficient added to a component of flux due to electrical forces. 2. The relation between bathing fluid Na concentraton and deltaC Na appeared sigmoid in form suggesting an allosteric mechanism for the transport step. 3. Transtubular potential difference, calculated from transepithelial Cl distribution ratios, did not appear constant at the various bathing fluid Na concentrations. Correcting for the effect of these potential differences on the value of each deltaC Na did not convert the sigmoid transport curve to a hyperbolic one, confirming the suggested allosteric nature of the active Na transport step. 4. Intracellular Na content varied linearly with bathing fluid Na concentrations implying free entry of this cation into the cell. This also suggests that the sigmoid transport curve is related to the properties of the active Na transport pump.

Animals