bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the electrical properties of arterial smooth muscle in normotensive rats and rats with deoxycorticosterone acetate-salt-induced hypertension: Possible involvement of (Na+-K+-Cl−) co-transport
Authors: Davis J. P. L. , Chipperfield A. R. , Harper A. A. 
Published: August 2015

1. Hypertension was induced in male Sprague-Dawley rats by left unilateral nephrectomy and deoxycorticosterone acetate-salt administration. After 5 weeks, arterial systolic blood pressure was significantly elevated in these animals (191.5 ± 6.0 mmHg, mean ± sd, n = 17) compared with age-matched, unoperated control animals (134.0 ± 4.2 mmHg, n = 8, P &lt; 0.001).
2. The membrane potential of femoral artery vascular smooth muscle measured in vitro was −55.1 ± 6.3 mV (mean ± sd, n = 154) for normotensive and −50.8 ± 5.7 mV (n = 82) for hypertensive animals. The difference in membrane potential was significant (P &lt; 0.001).
3. The relationship between the log of the extracellular K+ concentration and membrane potential was nonlinear over the extracellular K+ concentration range 2.5–20 mmol/l, and showed a small positive shift with hypertension.
4. Tenfold reductions in the extracellular concentrations of Na+ or Cl− resulted in a membrane potential hyperpolarization in vascular smooth muscle from normotensive animals (4.9 ± 2.0 mV, n = 13 and 12.1 ± 1.3 mV, mean ± sd, n = 14, respectively). In vascular smooth muscle from hypertensive animals, the hyperpolarization in low-Na+ media was significantly increased to 12.2 ± 2.6 mV (mean ± sd, n = 5), but that in low-Cl− media was unaffected (2.7 ± 1.6 mV, n = 6).
5. The loop diuretic, bumetanide (10 μmol/l), hyperpolarized the membrane potential in vascular smooth muscle from both normotensive and hypertensive rats, but not in low-Na+ or low-Cl− media. This effect was significantly increased in hypertension, from 1.8 ± 0.7 mV (mean ± sd, n = 8) to 4.0 ± 1.0 mV (n = 5).
6. These results suggest that in these cells, K+ permeability ≫ Na+ permeability &gt; Cl− permeabilty, and that the membrane potential is determined principally by the K+ permeability. In deoxycorticosterone acetate-salt hypertension, the membrane potential is depolarized, Na+ permeability is substantially increased, and there appears to be an increase in the activity of the (Na+-K+-Cl−) co-transporter.
Oral sodium regulates extrahepatic metabolism of vasoactive intestinal peptide
Authors: Hawley C. M. , Duggan K. A. , MacDonald G. J. , Shelley S. 
Published: August 2015

1. Gastric sodium loading causes release of vasoactive intestinal peptide from the gastrointestinal tract and, in rabbits on a low-sodium diet, an apparent decrease in metabolism of vasoactive intestinal peptide by the liver. Other workers have shown that decreased hepatic metabolism of vasoactive intestinal peptide is accompanied by an increase in pulmonary metabolism of vasoactive intestinal peptide. To determine whether oral sodium loading also regulates non-hepatic metabolism of vasoactive intestinal peptide, metabolic clearance studies of intravenously infused vasoactive intestinal peptide were performed. These studies were performed in male New Zealand White rabbits equilibrated on normal- and low-sodium diets before and after an acute gastric sodium load of 1.5 mmol/kg.
2. The metabolic clearance rate of vasoactive intestinal peptide was significantly greater in rabbits on the low-sodium diet than in rabbits on the normal-sodium diet both before (P &lt; 0.025) and after (P &lt; 0.05) a gastric sodium load. Significant decreases in metabolic clearance rate were observed in response to the sodium load in both dietary groups (normal-sodium diet, P &lt; 0.05; low-sodium diet, P &lt; 0.025). The theoretical secretion rate of vasoactive intestinal peptide also fell after the gastric sodium load in rabbits on the low-sodium diet (P &lt; 0.05) and the half-life of vasoactive intestinal peptide increased (P &lt; 0.01).
3. We conclude that the non-hepatic metabolism of vasoactive intestinal peptide appears to be responsive to both chronic dietary sodium intake and acute gastric sodium loading.
Effect of acute administration of gliclazide on the glucose sensitivity of pancreatic B-cells in healthy subjects
Authors: Veneman T. F. , van Haeften T. W. , van der Veen E. A. 
Published: August 2015

1. Sulphonylurea derivatives are commonly used in the treatment of non-insulin-dependent diabetes mellitus. It is, however, unclear whether the hypoglycaemic effect of sulphonylurea derivatives is additive to the effect of glucose, or whether sulphonylurea derivatives act by increasing B-cell glucose sensitivity.
2. We assessed the effect of gliclazide on glucose-stimulated insulin secretion in eight healthy volunteers. Sixty minute hyperglycaemic glucose clamps (blood glucose levels of 8, 11 and 32 mmol/l) were performed, with and without prior administration of gliclazide (80 mg) 90 min before the glucose clamp.
3. Dose-response characteristics were assessed with a modified Michaelis-Menten equation. The Vmax. (maximal B-cell responsiveness) was not significantly changed (1.5 ± 0.1 versus 1.3 ± 0.2 and 5.0 ± 0.5 versus 4.8 ± 0.5 mmol/l for the first- and second-phase insulin secretion, respectively), whereas the ED50 (half-maximally stimulating blood glucose concentration) was significantly decreased by gliclazide for first-phase insulin secretion (7.6 ± 0.3 versus 9.1 ± 0.6 mmol/l) but not for second-phase insulin secretion (12.0 ± 0.5 versus 12.3 ± 0.5 mmol/l).
4. We conclude that gliclazide indeed leads to a shift to the left of the dose-response curve of first-phase insulin release in vivo without a change in Vmax., which indicates an apparent enhancement of B-cell glucose sensitivity.
Effects of dietary Ca2+ on erythrocyte Na+-transport systems in spontaneously hypertensive rats
Authors: Fujito K. , Yokomatsu M. , Ishiguro N. , Numahata H. , Tomino Y. , Koide H. 
Published: August 2015

1. The purpose of this study was to determine the effect of dietary Ca2+ intake on blood pressure and erythrocyte Na+ transport in spontaneously hypertensive rats.
2. Spontaneously hypertensive rats and Wistar-Kyoto rats were fed diets with three different Ca2+ contents, 0.1% (low-Ca2+ diet), 0.6% (normal-Ca2+ diet) and 4.0% (high-Ca2+ diet), between 6 and 20 weeks of age. At 20 weeks of age, the levels of erythrocyte Na+ efflux, as well as Na+ and K+ contents in erythrocytes, were measured.
3. On the low-Ca2+ diet, spontaneously hypertensive rats showed an enhancement of hypertension. Conversely, on the high-Ca2+ diet, they showed an attenuation of the increase in blood pressure. Spontaneously hypertensive rats had a lower erythrocyte Na+ content and increased activity of the Na+ pump at higher levels of dietary Ca2+. Passive Na+ permeability and Na+-K+ co-transport were similar in spontaneously hypertensive rats on the low-, normal- and high-Ca2+ diets. There were no significant differences in blood pressure and in Na+ pump activity in WKY on the three different diets.
4. It is concluded that dietary Ca2+ might affect the regulation of blood pressure in spontaneously hypertensive rats by changing the activity of Na+ pump in the cell membrane.
Effect of insulin on intracellular pH and phosphate metabolism in human skeletal muscle in vivo
Authors: Taylor D. J. , Coppack S. W. , Cadoux-Hudson T. A. D. , Kemp G. J. , Radda G. K. , Frayn K. N. , NG L. L. 
Published: August 2015

1. 31P nuclear magnetic resonance spectroscopy and the hyperinsulinaemic-euglycaemic clamp were used simultaneously to assess the effect of insulin on intracellular pH and the major phosphorus-containing metabolites of normal human skeletal muscle in vivo in four normal subjects.
2. Insulin and glucose were infused for 120 min. Plasma insulin increased approximately 10-fold over pre-clamp levels (5.6 ± 0.9 m-units/l pre-clamp and 54 ± 5 m-units/l over the last hour of infusion; mean ± sem, n = 4). Plasma glucose concentration did not change significantly (5.4 ± 0.2 mmol/l pre-clamp and 5.5 ± 0.1 mmol/l over the last hour of infusion).
3. Insulin and glucose infusion resulted in a decline in the intracellular pH of forearm muscle of 0.027 ± 0.007 unit/h (P &lt; 0.01), whereas in control studies of the same subjects, pH rose by 0.046 ± 0.005 unit/h (P &lt; 0.001).
4. In the clamp studies, intracellular inorganic phosphate concentration rose by 18%/h, whereas ATP, phosphocreatine and phosphomonoester concentrations did not change. In plasma, inorganic phosphate concentration was 1.16 ± 0.05 mmol/l before infusion, and this decreased by a mean rate of 0.14 mmol h−1 l−1. No change was observed in any of these intracellular metabolites in the control studies.
5. The results show that, under physiological conditions, insulin does not raise intracellular pH in human muscle, and thus cannot influence muscle metabolism by this mechanism. The results also suggest that insulin causes a primary increase in the next flux of inorganic phosphate across the muscle cell membrane.
Bicarbonate reabsorption and electrophysiology of proximal tubules in uninephrectomized rats
Authors: Limongi Dirce M. Zanetta , Cassola Antonio Carlos , Woronik Viktoria , Malnic Gerhard 
Published: August 2015

1. The kinetics of acidification of luminal fluid in hypertrophied proximal tubules after unilateral nephrectomy was studied by stationary microperfusion and continuous measurement of luminal pH with antimony microelectrodes.
2. Trans-epithelial and basolateral membrane electrical potential differences were measured in order to detect modifications in electrogenic transport mechanisms under these conditions.
3. The values of stationary pH and HCO−3 concentration were significantly lower, the mean acidification half-time was not different and net reabsorptive HCO−3 fluxes in proximal tubules were significantly increased in uninephrectomized rats. According to an electrical analogue model, these results suggest (a) a reduction in the internal series resistance of the H+ pump, caused perhaps by an increased density of pump sites, and (b) an increase in the protonmotive force of the pump.
4. The trans-epithelial electrical potential difference measured in free flow conditions was significantly more lumen-positive in uninephrectomized rats. The trans-epithelial electrical potential difference measured during intraluminal perfusion with Ringer solution containing 30 mmol/l HCO−3 was significantly more negative in all groups studied. In uninephrectomized rats treated with acetazolamide, the trans-epithelial electrical potential difference was more lumen-negative than that in untreated uninephrectomized rats. These results are compatible with a steeper transepithelial Cl− gradient as well as with electrogenic, active H+ secretion.
5. There was no significant difference in the basolateral electrical potential difference between control and uninephrectomized rats.
6. In conclusion, our data show an increase in the transport rates of HCO−3 in the proximal tubule of uninephrectomized rats, which may be due to an increase in the density of transporters in the brush-border membrane, and an increased ability of the transport mechanism to create H+ gradients.
Calcium and phosphate metabolism in acute falciparum malaria
Authors: DAVIS T. M. E. , Pukrittayakamee S. , Woodhead J. S. , Holloway P. , Chaivisuth B. , White N. J. 
Published: August 2015

1. Mineral homoeostasis was investigated in 172 Thai adults with acute falciparum malaria at presentation (87 males, 85 females; mean age 30 years), and prospectively in a subgroup of 10 severely ill patients.
2. Mild, asymptomatic hypocalcaemia (corrected plasma calcium concentration 1.79–2.11 mmol/l) was found in 61 cross-sectional study patients (35.5%), with no difference between those with uncomplicated (2.16 ± 0.10 mmol/l, mean ± sd, n = 89) and severe (2.18 ± 0.15 mmol/l, n = 83, P = 0.36) infections. Six prospectively studied patients were hypocalcaemic during treatment; simultaneous serum intact parathormone concentrations were inappropriately low (&lt; 5.0 pmol/l), but rose in three patients to high levels (11.8–16.4 pmol/l) on the fifth day.
3. Plasma phosphate concentration was decreased (&lt; 0.80 mmol/l) on admission in 74 patients (43.0%) and increased (&gt; 1.45 mmol/l) in 15 (8.7%). Severe phosphate depletion (plasma phosphate concentration &lt; 0.30 mmol/l) occurred in 14 patients, of whom 11 had severe infections. Serum phosphate concentrations in the prospective study patients on admission (0.59 ± 0.23 mmol/l) correlated significantly with the simultaneous renal threshold phosphate concentration (0.68 ± 0.33 mmol/l; r = 0.607, P &lt; 0.025) and both parameters rose in parallel during treatment.
4. Plasma magnesium concentrations were normal (0.75–1.05 mmol/l) in 108 patients (62.8%); 45 cases (26.1%) had hypermagnesaemia and 19 (11.0%) had hypomagnesaemia.
5. These data suggest that mild hypocalcaemia is common in malaria regardless of disease severity; a depressed parathormone response may contribute. Despite malaria-associated haemolysis, hypophosphataemia is also common, but can be severe. Phosphate replacement should therefore be considered where strict monitoring of plasma phosphate concentrations is feasible.
Basal metabolic rate, body composition and whole-body protein turnover in Indian men with differing nutritional status
Authors: Soares M. J. , Piers L. S. , Shetty P. S. , Robinson S. , Jackson A. A. , Waterlow J. C. 
Published: August 2015

1. Three groups of adult men were studied in Bangalore, India: two groups were controls who had been receiving an adequate diet. Of these, one group, designated ‘normal weight controls', had a mean body mass index of 22; the other group, ‘underweight controls', had a mean body mass index of 16.7. The third group consisted of poor labourers, whose daily food intake had been less than 10 MJ and whose mean body mass index was 16.6. Previous studies had shown that such men had a lower basal metabolic rate than well-nourished Indian control subjects.
2. The object of the present study was to find out whether a reduced rate of protein turnover, measured after a single dose of [15N]glycine, contributed to a lower basal metabolic rate. It was found, however, that after adjusting for body weight and fat-free mass by analysis of co-variance there was no significant difference in basal metabolic rate between the three groups. Adjusted rates of protein synthesis were higher in the underweight controls and the undernourished labourers than in the normal weight controls, but not significantly so.
3. Estimates based on creatinine excretion showed that within the fat-free mass the underweight groups had a higher proportion of non-muscle to muscle mass. This may explain the somewhat higher rates of protein turnover in these groups.
4. Nitrogen flux (Q) was determined from 15N abundance in two end products, urea (QU) and ammonia (QA). In the underweight and undernourished groups the ratio QU/QA was increased compared with the normal weight group. This fits in with the finding of a greater proportion of visceral mass in the underweight subjects and with the compartmental model of protein metabolism that we have previously proposed.
Feedback-mediated reduction in glomerular filtration during acetazolamide infusion in insulin-dependent diabetic patients
Authors: Hannedouche T. , Lazaro M. , Delgado A. G. , Boitard C. , Lacour B. , Grünfeld J.-P. 
Published: August 2015

1. A sustained high glomerular filtration rate in diabetes mellitus is associated with increased proximal reabsorption, suggesting alterations in the tubulo-glomerular feedback system. To test this hypothesis, renal function was studied in eight control subjects and 14 recent-onset euglycaemic insulin-dependent diabetic patients before and after infusion of the carbonic anhydrase inhibitor, acetazolamide (5 mg/kg body weight).
2. Acetazolamide induced a dramatic fall in glomerular filtration rate in both diabetic patients and control subjects (from 138 ± 5 to 114 ± 4 and from 127 ± 3 to 113 ± 2 ml min−1 1.73 m−2, respectively, P &lt; 0.0001). This fall in glomerular filtration rate was strongly correlated with the acetazolamide-induced decrease in absolute proximal reabsorption calculated by using lithium clearance.
3. To further assess the potential role of angiotensin II in the acetazolamide-induced tubulo-glomerular feedback response, 11 additional diabetic patients were investigated before and after the administration of acetazolamide plus the angiotensin-converting enzyme inhibitor, enalaprilat (1.25 mg intravenously). Despite the effective blockade of angiotensin II formation and a slight decrease in renal vascular resistance, the glomerular filtration rate fell significantly and by a similar magnitude as seen with acetazolamide alone.
4. These results indirectly suggest that there is an altered basal tubulo-glomerular feedback system in diabetic patients but a normal response to the increase in distal delivery. No convincing role for an angiotensin II-mediated effect on the afferent limb of the tubulo-glomerular feedback response could be demonstrated.
Effect of aluminium on urinary acidification in the rat: influence of parathyroid hormone
Authors: Gil F. Zaladek , Costa Silva V. L. , Cavanal M. F. 
Published: August 2015

1. The influence of thyroparathyroidectomy and/or acidosis on renal function and specifically on acid excretion was studied in rats treated with a cumulative dose of 2 mg of aluminium.
2. Aluminium-treated and non-treated thyroparathyroidectomized rats showed a significant decrease in glomerular filtration rate and in the urinary/plasma inulin ratio without alteration in net acid excretion.
3. Non-treated thyroparathyroidectomized acidotic rats showed a significant fall in the amount of ammonium excreted and in overall acid excretion, suggesting that parathyroid hormone participates in an important way in the defence against metabolic acidosis.
4. The effects of acidosis, thyroparathyroidectomy and aluminium treatment on renal function parameters were not additive, suggesting a common final mechanism. In normal or acidotic aluminium-treated rats, thyroparathyroidectomy had no effect on renal acid excretion, suggesting that aluminium even in low doses inhibited the action of PTH on the renal tubule.
5. After exposure to aluminium, the relative inhibition of PTH on the renal tubule may become an additional factor that could contribute to the worsening of clinical conditions in which an inappropriate retention of acid loads can occur.
Urinary excretion of digoxin-like immunoreactive factor and arginine-vasopressin in hyper- and hypo-thyroid rats
Authors: Vargas Felix , Baz Maria J. , de D. Luna Juan , Andrade Jesus , Jodar Esteban , Haro Jose M. 
Published: August 2015

1. Urinary excretion of digoxin-like immunoreactive factor and arginine-vasopressin and other parameters related to salt and water metabolism were studied in hyper- and hypo-thyroid rats after different tests.
2. Urinary excretion of arginine-vasopressin was increased in hyperthyroid and reduced in hypothyroid rats with respect to controls, in response to water deprivation or a hypertonic saline load.
3. Control and hypothyroid rats showed the highest urinary excretion of digoxin-like immunoreactive factor after a hypertonic saline load. However, hyperthyroid rats had the highest urinary levels of digoxin-like immunoreactive factor under normal conditions.
4. From these results it is suggested that: (a) hyper- and hypo-thyroid rats exhibit hyper- and hypo-responsiveness of arginine-vasopressin secretion to osmotic stimuli, respectively; (b) an unidentified digoxin-like immunoreactive factor measured in unextracted rat urine may be related to diuresis and natriuresis in control and hypothyroid rats; however, dissociation between this factor and natriuresis is observed in hyperthyroid rats.
Low-concentration ouabain does not inhibit noradrenaline-induced contraction of human resistance arteries
Authors: Woolfson Robin G. , Richards Nicholas T. , Poston Lucilla 
Published: August 2015

1. Using a Mulvany-Halpern myograph to measure changes in isometric tension, we have investigated the effect of ouabain on noradrenaline-induced contraction of human subcutaneous resistance arteries.
2. Low concentrations of ouabain (10 nmol/l or less) were shown not to alter vascular smooth muscle contractility or sensitivity to noradrenaline.
3. In contrast, higher concentrations of ouabain (100 nmol/l or more) were found to depress vascular smooth muscle contractility and to reduce the sensitivity of the noradrenaline concentration-response relationship.
4. These findings may have implications regarding the presence of an endogenous inhibitor of the sodium pump in essential hypertension and in pregnancy-associated hypertension.
Stanozolol stimulates remodelling of trabecular bone and net formation of bone at the endocortical surface
Authors: Benéton M. N. C. , Yates A. J. P. , Rogers S. , McCloskey E. V. , Kanis J. A. 
Published: August 2015

1. We studied the mechanism of action of the anabolic steroid, stanozolol, in 23 patients with osteoporosis, using a combination of biochemical and histomorphometric techniques.
2. Treatment with stanozolol (5 mg/day) for 1 year was associated with a marked and significant decrease in the fasting urinary excretion of calcium (P &lt; 0.01) but not with changes in the serum concentrations of calcium and phosphate, the serum activity of alkaline phosphatase, the renal tubular reabsorption of calcium or the urinary excretion of hydroxyproline.
3. Histological examination of trabecular bone showed an increase in bone turnover and the bone formation rate increased twofold (P &lt; 0.02). There were no significant changes in bone volume or wall thickness after treatment. Tetracycline labelling was used to discriminate bone structural units completed before and during treatment. Measurements of the wall thickness of those bone structural units formed during treatment showed no significant change.
4. Measurements made on the endocortical surface also showed an increase in bone turnover, but in contrast to trabecular bone, the bone structural units formed at endocortical sites during treatment had a significantly greater wall thickness than those formed before treatment (P &lt; 0.05).
5. We conclude that stanozolol increases the turnover of trabecular bone and increases the endocortical apposition of bone.