bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Sodium Intake: A Determinant of Postprandial Plasma Sodium Concentration in the Dog
Authors: Schneider E. G. , Gleason Sarah D. , Zucker A.
Published: August 2015

1. The effect of dietary sodium intake on pre-and post-prandial plasma sodium concentrations and on the pattern of sodium and potassium excretion was determined in conscious female dogs, who were allowed free access to water and were fed on commercial low sodium diets supplemented with 0, 50, 100 or 250 mmol of sodium chloride/day for 6 days.

2. The preprandial plasma sodium concentration was not altered by the dietary sodium intake. However, the 4 h postprandial plasma sodium concentration was linearly related to the magnitude of dietary sodium intake, whereas the 8 h postprandial plasma sodium concentration was elevated only in dogs receiving 250 mmol of sodium/day.

3. The (0–8 h/0–24 h) ratio for urinary sodium excretion was significantly correlated with both the dietary sodium intake and the postprandial increase in plasma sodium concentration.

4. The 24 h excretion of potassium was not markedly affected by the dietary sodium intake; however, the (0–8 h/0–24 h) ratio for potassium excretion was significantly correlated with both the dietary sodium intake and the (0–8 h/0–24 h) ratio for sodium excretion.

5. These data indicate that: (a) postprandial increases in plasma sodium concentration need to be considered when evaluating the mechanisms involved in the daily regulation of sodium balance; (b) the daily pattern of potassium excretion is closely linked to the dietary sodium intake.
Erythrocyte Metabolism in Patients on Haemodialysis and Continuous Ambulatory Peritoneal Dialysis
Authors: Summerfield G. P. , Bellingham A. J. , Manlove L. , Forbes A. M. , Goldsmith H. J.
Published: August 2015

1. Erythrocyte metabolism was investigated and glycolytic intermediates were measured in nine patients with chronic renal failure who were subsequently treated with haemodialysis. The same' investigations were performed in nine patients on continuous ambulatory peritoneal dialysis (CAPD) who had previously been treated with intermittent peritoneal dialysis (IPD) (eight patients) or dietary restriction (one patient).

2. The patients who received haemodialysis had a partially compensated metabolic acidosis before treatment. With haemodialysis, plasma phosphate (Pi) fell and base excess, erythrocyte 2,3–diphosphoglycerate (2,3–DPG), glucose consumption and lactate production rose significantly. In this group the most important influence on erythrocyte metabolism was base excess. The pattern of erythrocyte glycolytic intermediates showed that the rise in 2,3–DPG with haemodialysis was brought about within the Rapoport—Luebering shunt; there was no statistically significant decrease in haemoglobin—oxygen affinity.

3. The patients who received CAPD were not acidotic before starting this form of treatment. With CAPD, there was a significant increase in haemoglobin and fall in plasma phosphate, erythrocyte 2,3–DPG and glucose consumption. The major factors influencing erythrocyte metabolism in this group were plasma phosphate and haemoglobin concentration. The fall in 2,3–DPG was produced by inhibition of 6-phosphofructokinase (EC 2.7.1.11); despite this fall, haemoglobin-oxygen affinity was not affected.
Erythrocyte Sodium Transport in Chronic Renal Failure
Authors: Swaminathan R. , Clegg G. , Cumberbatch M. , Zareian Z. , McKenna F.
Published: August 2015

1. Erythrocyte sodium, sodium transport (ouabain-sensitive efflux rate of sodium, oMosNa, and ouabain-sensitive efflux rate constant of sodium, oMosNa), sodium-potassium activated ouabain-sensitive adenosine triphosphatase (Na+, K+-ATPase) activity and [3H]ouabain-binding capacity were measured in 15 patients with chronic renal failure and in 10 healthy subjects.

2. As a group, patients with chronic renal failure had a lower erythrocyte sodium and oMosNa compared with healthy subjects.

3. When patients were divided according to their erythrocyte sodium (greater or less than 4 mmol/kg of cells), in the group of patients whose erythrocyte sodium was less than 4 mmol/kg of cells (group A) the oMosNa was higher than that in healthy subjects and the oMosNa, Na+, K+-ATPase activity and [3H]ouabain-binding capacity were the same as those in healthy subjects. In the subgroup of patients with renal failure whose erythrocyte sodium content was greater than 4 mmol/kg of cells (group B) the oMosNa was less and plasma urea concentration higher than in group A and Na+, K+-ATPase activity, [3H]ouabain-binding capacity and oMosNa were lower than in healthy subjects.

4. These results suggest that in early chronic renal failure there is stimulation of ‘sodium pumps’ (without alteration in their number), which causes a lowering of erythrocyte sodium content, and that as the disease progresses there is inhibition of the ‘sodium pumps’ as well as a reduction in membrane permeability so that erythrocyte sodium is near normal.
Decrease in the Tubular Reabsorption of Calcium with Evidence for Compensatory Hyperparathyroidism in X-Linked Hypophosphataemia in Mice
Authors: Mühlbauer R.C. , Bonjour J.-P. , Fleisch H.
Published: August 2015

1. It has been suggested that a dominant mutation in the mouse is a suitable model for the most frequent form of human vitamin D-resistant rickets, X-linked hypophosphataemia. The mutant mice have reduced tubular reabsorption of phosphate, hypophosphataemia, rachitic bone lesions, moderate dwarfism and mild hypocalcaemia.

2. The present work shows that male hypophosphataemic (HYP/Y) mice have a decrease in the tubular capacity to reabsorb calcium as compared with normal littermates (+/Y). This decrease appears to be related to the phosphate status of the animals, since it is much more pronounced when the animals are fed on a low phosphorus diet.

3. The decrement in the tubular reabsorption and plasma concentration of calcium in HYP/Y mice is not accompanied by an augmentation in the absolute urinary excretion of calcium. It is associated with an increase in the urinary excretion of cyclic AMP. Furthermore, removal of the thyroparathyroid glands leads to much larger fall in the plasma concentration of calcium in HYP/Y than in +/Y mice.

4. Thus HYP/Y mice, when compared with normal littermates, have decreased tubular reabsorption of calcium with no apparent increase in the mobilization of calcium from intestinal and body sources as reflected by the absence of an augmentation in the absolute amount of calcium excreted in the urine. These findings could account for a propensity to hypocalcaemia which would be partially compensated by secondary hyperparathyroidism. This could explain the increase in urinary cyclic AMP excretion and the exaggerated hypocalcaemic response to removal of the parathyroid glands observed in murine X-linked hypophosphataemia.
Alveolar Gas Mixing Efficiency in the Human Lung
Authors: Cumming G. , Guyatt A. R.
Published: August 2015

1. The lung nitrogen from ten normal nonsmoking subjects and ten patients with chronic respiratory disease was washed out by inspiration of 21% oxygen and 79% argon, whilst expired nitrogen concentration was measured with a mass spectrometer and flow with a box-bag system, and the quantity of nitrogen in each expirate calculated with a Varian 73 digital computer and plotted against expired volume.

2. The resulting curve from each breath was handled either as a linear or a polynomial regression, the intercept on the abscissa being designated the series dead space volume (VDS). This dead space has also been measured by the Fowler method and by the mathematical differentiation of phase II.

3. The nitrogen recovered from the first breath varied between 190 ml and 584 ml and this has been expressed as a percentage of that volume predicted assuming perfect alveolar mixing; this has been called the alveolar gas mixing efficiency for nitrogen. The mean values for alveolar mixing efficiency computed from the four different series dead space volumes were 89.8%, 90.8%, 89.0% and 85.7%. This suggests that the value of series dead space used in computing mixing efficiency is not of great importance, and any of the four methods gives satisfactory results.

4. The data from multi-breath washout were also similarly expressed as a percentage efficiency, making the results from the two methods directly comparable. The median value for alveolar gas mixing efficiency by the single breath test was 89%, and for the multi-breath test about 76%. The latter was apparently more discriminating for ventilatory defect. In patients the values were respectively 73% and 40%.
Effects of Saralasin Infusion on Bilateral Renal Function in Two-Kidney, One-Clip Goldblatt Hypertensive Rats
Authors: Huang Wann-Chu , Ploth D. W. , Navar L. G.
Published: August 2015

1. Previous studies have shown that administration of converting enzyme inhibitor (CEI, SQ 20 881) to two-kidney, one-clip Goldblatt hypertensive (GH) rats clipped for 3–4 weeks resulted in marked increases in glomerular filtration rate (GFR), water and sodium excretion by the non-clipped kidneys. The clipped kidneys exhibited reduced function that was due, in part, to the reductions in arterial pressure. To evaluate further the hypothesis that the renal responses to CEI were due primarily to the inhibition of angiotensin II rather than other factors, we infused the angiotensin II competitive blocker, saralasin, into GH rats under sodium pentobarbital anaesthesia and examined renal haemodynamics and excretory function of each kidney before and during saralasin infusion and after cessation of saralasin infusion.

2. Saralasin reduced mean arterial blood pressure from 164 ± 4 to 124 ± 4 mmHg. Despite the profound fall of arterial pressure, significant increases in renal blood flow from 5.82 ± 0.22 to 9.15 ± 0.76 ml/min and glomerular filtration rate from 1.46 ± 0.10 to 2.18 ± 0.14 ml/min were observed in the non-clipped kidneys. Renal vascular resistance decreased from 2.34 (± 0.14) × 105 to 1.17 (± 0.19) × 105 kPa l−1 s [2.34 (± 0.14) × 106 to 1.17 (± 0.19) × 106 dyn s cm−5]. Also, concomitant diuresis and kaliuresis and a delayed natriuresis occurred.

Correspondence: Dr L. G. Navar, University of Alabama in Birmingham Medical Center, University Station, 727 CDLD Bldg, Birmingham, Alabama 35294, U.S.A.

3. The clipped kidneys exhibited reductions in renal blood flow, GFR and excretory function during saralasin infusion.

4. Normal rats receiving the identical dose of saralasin responded with a slight but significant decrease in arterial pressure. The increases in renal blood flow and GFR were less than those observed in the non-clipped kidneys of hypertensive rats.

5. These data provide further support to the hypothesis that an angiotensin II-mediated elevation in renal vascular resistance and impairment of renal function exist in the non-clipped kidneys of GH rats.
Acute Haemodynamic and Hormonal Effects of Captopril are Diminished by Indomethacin
Authors: Witzgall H. , Hirsch F. , Scherer B. , Weber P. C.
Published: August 2015

1. The acute haemodynamic and hormonal effects of 100 mg of captopril (SQ 14.225) orally were tested in twelve healthy men in the sodium replete state before and after indomethacin pre-treatment.

2. Without indomethacin, mean arterial blood pressure was reduced at 30 and 60 min after captopril (P < 0.02). Heart rate did not change during the whole experiment. Although plasma renin activity (PRA) increased (P < 0.002), plasma and urinary aldosterone and plasma 18-hydroxycorticosterone (18-OH-B) decreased after captopril (P < 0.02). Prostaglandin (PG) E2, sodium and potassium excretion rates remained constant after captopril.

3. Under indomethacin pretreatment, the fall in mean arterial blood pressure was less than without indomethacin at 30 and 60 min after captopril (P < 0.05). Heart rate was constantly lower than without indomethacin during the whole experiment (P < 0.05). Indomethacin pretreatment decreased basal PGE2 excretion (P < 0.02) and baseline PRA as well as the increase in PRA after captopril (P < 0.05). Control mineralocorticoid levels were significantly lower than without indomethacin. In indomethacin-pretreated subjects, aldosterone did not further decrease after captopril, and 18-OH-B fell only slightly.

4. Without indomethacin pretreatment a significant, positive correlation was found between PRA values before captopril and the maximum decrease of mean arterial blood pressure after captopril. Under indomethacin pretreatment this correlation was no longer demonstrable. The results suggest that prostaglandins may contribute to the haemodynamic and hormonal actions of captopril.
Sympathomimetic Drugs Stimulate the Output of Secretory Glycoproteins from Human Bronchi In Vitro
Authors: Phipps R. J. , Williams I. P. , Richardson P. S. , Pell J. , Pack R. J. , Wright N.
Published: August 2015

1. We describe a method for supporting pieces of human bronchi in Ussing chambers, for radiolabelling the contents of the secretory cells with 35S, and for collecting radiolabeled macromolecules secreted on to the luminal aspect of the tissue. This method has previously been used to study airway secretions in animals [R. J. Phipps, J. A. Nadel & B. Davis, American Review of Respiratory Disease, (1980) 121, 359–365]. Evidence is given that the radiolabelled molecules are secretory glycoproteins, probably mucus glycoproteins.

2. Phenylephrine, an α-adrenoceptor agonist, increased the rate at which the bronchi secreted radiolabeled glycoproteins. Thymoxamine, an α-adrenoceptor antagonist, blocked this effect but propranolol, a β-adrenoceptor antagonist, did not.

3. Dobutamine, a β1-adrenoceptor agonist, increased the rate of secretion of radiolabeled glycoproteins. Propranolol blocked this but thymoxamine did not.

4. Salbutamol, a β2-adrenoceptor agonist, also increased the rate of secretion of radiolabeled glycoproteins. Propranolol blocked this effect.

5. We conclude that both α and β-adrenoceptor agonists increase the rate of glycoprotein secretion in human bronchi in vitro and that this almost certainly means that they increase the rate of mucus secretion.
The Influence of Indomethacin on Renal Concentrating and Diluting Capacity in Sickle Cell Nephropathy
Authors: de Jong P. E. , de Jong-Van Den Berg L. T. W. , de Zeeuw D. , Donker A. J. M. , Schouten H. , van Eps L. W. Statius
Published: August 2015

1. The effects of indomethacin on water excretion during both vasopressin stimulation and inhibition were studied in control subjects and in patients with sickle cell anaemia.

2. In the control group as well as in the group of patients with sickle cell anaemia sodium and urea retention occurred after indomethacin in the water-depleted state. During water loading, indomethacin induced sodium retention without urea reabsorption.

3. In healthy volunteers indomethacin increased urinary osmolality during water deprivation, but not after water loading. In contrast, in patients with sickle cell anaemia indomethacin caused a rise in urinary osmolality during water loading, but not after water deprivation.

4. The findings support the view that indomethacin promotes solute reabsorption in the distal tubule.

5. From our observations we conclude that renal prostaglandins are not involved in the urinary concentrating defect of patients with sickle cell anaemia. On the other hand, the normal diluting capacity in sickle cell anaemia appears to depend on renal prostaglandins.
Bile Acid Profiles of Human Serum and Skin Interstitial Fluid and Their Relationship to Pruritus Studied by Gas Chromatography–Mass Spectrometry
Authors: Bartholomew T. C. , Summerfield J. A. , Billing B. H. , Lawson A. M. , Setchell K. D. R.
Published: August 2015

1. Pruritus was assessed in 19 patients by measurement of nocturnal limb movement.

2. Serum (nine pruritic, ten non-pruritic) and interstitial fluid (five pruritic, three non-pruritic) bile acids were fractionated according to their mode of conjugation by using DEAP-Sephadex LH-20 and measured by gas chromatography—mass spectrometry.

3. No correlation was found between serum or interstitial fluid total bile acid or individual bile acid concentrations and pruritus. Bile acid profiles in the two groups of patients were similar and there was no correlation between pruritus and the conjugation pattern.

4. The bile acid profile of interstitial fluid reflected that of serum and a linear relationship was found between serum and interstitial fluid bile acid concentrations (r = 0·95, P < 0·001).

5. The proportion of bile acid sulphate in interstitial fluid was significantly smaller than that in serum (P < 0·025), where sulphates accounted for up to 46% of the total bile acids.

6. In three patients, a decrease in serum bile acid concentrations achieved by percutaneous transhepatic biliary drainage had little or no effect on pruritus.

7. These findings suggest that bile acids do not have a causative role in the pruritus of cholestatic liver disease.
Effect of Exercise on Gain of the Carotid-Sinus Reflex in Rabbits
Authors: Faris I. B. , Jamieson G. G. , Ludbrook J.
Published: August 2015

1. Blood pressure, heart rate and cardiac output were measured in six rabbits before, during and immediately after treadmill exercise. During the same periods the dynamic gain of the carotid-sinus baroreceptor reflex was estimated by creating a sinusoidal oscillation of carotid-distending pressure.

2. The average blood pressure did not change significantly during or after exercise, but heart rate and cardiac output rose markedly and there was a concomitant fall in systemic vascular resistance.

3. The reflex gain for blood pressure decreased by one-fifth during exercise, and the gains for heart rate and vascular resistance by two-fifths. Immediately after exercise the gains for all three variables decreased further, to between one-half and one-third of the resting values.

4. Our results indicate that during and after dynamic exercise the correction of a potential disturbance of blood pressure by the carotid-sinus baroreceptor reflex is decreased in magnitude or in speed.
Rates of New Bone Formation in Patients with Crush Fracture Osteoporosis
Authors: Reeve J. , Green J. R. , Hesp R. , Hulme Patricia
Published: August 2015

1. Calcium balances and formation rates of new bone measured with an improved tracer technique using 85Sr have been determined simultaneously in 21 patients with idiopathic osteoporosis and vertebral crush fractures.

2. A weak positive association was found between calcium balance and the kinetically measured calcium accretion rate, which is the sum of the true rate of bone formation and various long-term exchange processes.

3. The more negative balances were associated with significantly greater early loss of tracer taken up into bone by ‘accretion’, so that long-term (> 200 day) uptake was reduced.

4. This indicates that patients actively losing bone mineral have lower true rates of bone formation and higher rates of long-term exchange than their fellow patients who are more nearly in calcium equilibrium.

5. No statistically significant association was found between measured rates of bone resorption and calcium balance.
An Electrophysiological Study of the Posterior Abdominal Vagus Nerve in Man
Authors: Andrews P. L. R. , Taylor T. V.
Published: August 2015

1. The compound action potential was recorded in segments of posterior abdominal vagus removed from patients undergoing elective vagotomy and the conduction velocities of the major components were measured.

2. The conduction velocities ranged from 0·15 m/s to 3·9 m/s. The majority of compound potentials recorded had latencies appropriate to C fibre conduction.
The Mechanism of Urinary Kallikrein Excretion in the Rat
Authors: Seeber A. Martínez , Vila S. B. , Catanzaro O. L.
Published: August 2015

1. In male Wistar rats urinary kallikrein excretion was positively correlated with urinary flow and glomerular filtration rate (GFR).

2. Osmotic diuresis produced by a 30% (w/v) glucose solution increased urinary kallikrein, and a positive correlation between this variable and urine flow was observed. No correlation was observed with GFR.

3. The mechanism of urinary kallikrein excretion is interpreted as a wash-out effect of renal kallikrein.
Sodium Transport during the Natriuresis of Volume Expansion; a Study Using Peripheral Blood Leucocytes
Authors: Poston L. , Wilkinson S. , Sewell R. B. , Williams R.
Published: August 2015

1. Leucocyte sodium transport was investigated as a possible assay for the small molecular weight natriuretic material isolated from the urine of normal subjects who had undergone volume expansion by saline infusion.

2. This fraction (fraction four or FIV), inhibitory to sodium transport in several other assays, was also found to inhibit leucocyte sodium transport.

3. FIV isolated from the urine of five normal subjects undergoing the natriuresis of mineralocorticoid ‘escape’ was also found to be inhibitory to leucocyte sodium transport.

4. Leucocytes isolated from the blood of the same subjects during mineralocorticoid escape showed decreased sodium transport.
Diversity of Membrane Abnormalities in Spontaneous Hypertension
Authors: Yamori Y. , Nara Y. , Kanbe T. , Imafuku H. , Mori K. , Kihara M. , Horie R.
Published: August 2015

1. The membrane viscosity of erythrocytes and synaptosomal membranes from 3-month-old stroke-prone spontaneously hypertensive rats (SHRSP) was less than that of normotensive Wistar-Kyoto (WKY) rats.

2. The percentage noradrenaline release from synaptosomes in response to a low potassium ion concentration and the incorporation of noradrenaline into synaptosomes were significantly increased in 3-month-old SHRSP compared with WKY rats.

3. Cultured smooth muscle cells obtained from the aorta of SHRSP showed a greater Na+ influx and K+ efflux when Na+, K+-dependent ATPase was inhibited by ouabain than did smooth muscle cells from the aorta of WKY rats.

4. These results suggest that diverse membrane abnormalities are present in SHRSP, including changes in synaptosomal function and the ionic transport and permeability of smooth muscle cells. These changes may be part of the mechanisms of hypertension, whereas the changes in the erythrocytes may serve as genetic markers of hypertension.
Ca2+ Binding and Membrane Fluidity in Essential and Renal Hypertension
Authors: Orlov Sergei N. , Postnov Yuvenali V.
Published: August 2015

1. Ca2+-binding ability and membrane structure of red blood cells of patients with essential and renal hypertension were studied.

2. Ca2+-binding ability of the erythrocyte membrane of patients with essential hypertension was found to be reduced by 30% compared with that of normotensive controls.

3. The rate of lateral diffusion of pyrene in the erythrocyte membrane of patients with essential hypertension was reduced both in the lipid bilayer and in the region of annular lipid compared with that of normotensive patients.

4. There are no differences either in Ca2+-binding ability or in fluidity of the erythrocyte membrane of patients with chronic renal hypertension compared with that of normotensive individuals.
Studies on Aldosterone Responsiveness to Angiotensin II during Clinical Variations in Calcium Metabolism in Normal Man
Authors: Bianchetti M. G. , Beretta-Piccoli C. , Weidmann P. , Boehringer K. , Link L. , Morton J. J.
Published: August 2015

1. Angiotensin II was infused at stepwise increasing dose rates (2, 4 and 10 pmol min–1 kg–1) in 12 normal subjects. Infusions were performed in the presence of normocalcaemia, mild hypercalcemia induced by concomitant calcium gluconate infusion, and after 2 weeks of treatment with nifedipine.

2. Pre-infusion plasma levels of angiotensin II, renin or aldosterone were not altered by acute mild hypercalcaemia or administration of nifedipine. The angiotensin II-induced increases in plasma aldosterone were also similar under the three study conditions.

3. Variations in calcium metabolism occurring under clinical conditions appear to play a minor role in modulating the angiotensin II-dependent pathway of aldosterone regulation in normal man.
Renal Kallikrein Activity and Urinary Kallikrein Excretion in Rats with Experimental Renal Hypertension
Authors: Marin-Grez M. , Schaechtelin G. , Bönner G. , Speck G. , Ganten D. , Gross F.
Published: August 2015

1. Rats were made hypertensive by ligating the aorta between the origins of both renal arteries. Sham-operated animals served as controls. Urinary and renal kallikrein activities, as well as plasma and renal renin activities, were measured 8 and 90 days after surgery.

2. Blood pressure was 155 ± 6 mmHg on day 8 after aortic ligature and 142 ± 6 mmHg on day 90; in controls pressures were 107 ± 3 and 110 ± 5 mmHg respectively.

3. Eight days after aortic ligature, kallikrein activity in the ischaemic kidneys was about 6·5 times, and in the non-ischaemic kidneys almost 2 times, that in controls. After 90 days the kallikrein activity was reduced to one-half of that in the controls in the ischaemic kidneys and it was normal in the contralateral.

4. The urinary kallikrein excretion of hypertensive rats was about one-third of that of the controls at both 8 and 90 days after aortic ligature.

5. The plasma renin activity in hypertensive rats was approximately seven times that in control animals 8 days after aortic ligature and did not differ from the control value after 90 days. Renin activity in the kidneys showed the same pattern as in other models of renovascular hypertension: elevation in the ischaemic kidney and reduction in the non-ischaemic one.
Effects of Frusemide on the Renal Kallikrein–Kinin System of the Rat
Authors: Bönner G. , Beck D. , Deeg M. , Marin-Grez M. , Gross F.
Published: August 2015

1. In male Wistar rats, three doses of frusemide (0·5, 5·0 and 50·0 mg/kg) were injected subcutaneously. A dose-related increase in urine flow and natriuresis occurred, whereas there was a biphasic response in kallikrein excretion with an initial, dose-related transient increase and a secondary reduction. When the urine losses were replaced by the infusion of 0·9% NaCl solution, the biphasic response of urinary kallikrein excretion was maintained.

2. In all experiments, urinary excretion of kallikrein correlated with the excretion of potassium. Frusemide enhanced the excretion of kinins, which correlated with the urine volume and the natriuresis, but not with kallikrein excretion.

3. In contrast to the initially increased excretion of kallikrein, kallikrein activity in the renal cortex remained unchanged or was even reduced. Kininogen content of the perfused tissue of the renal cortex did not vary throughout the experiment, but decreased markedly in the non-perfused tissue of the cortex 30 min after the injection of frusemide.

4. It is concluded that forced diuresis induced by frusemide causes a ‘wash out’ of renal kallikrein in urine, probably not indicating the true changes in the activity of the renal kallikrein-kinin system within the kidney. Kinin excretion in urine was not correlated with kallikrein excretion but with changes in diuresis. Thus it might be suggested that the renal kallikrein-kinin system could be involved by kinins in the regulation of renal water and sodium excretion as well as of renal plasma flow.
Diffuse Structural Abnormalities in Cell Membranes from Genetically Hypertensive Rats: A Fluorescence Polarization Study
Authors: Aragon Inès , Montenay-Garestier Thérèse , Nunez Marie-Aude , Pernollet Marie-Gabrielle , Nunez Anne-Marie , Ben-Ishay Drori , Meyer Philippe , Helene Claude
Published: August 2015

1. Diphenylhexatriene was used as a fluorescence probe to detect structural differences between membranes from genetically hypertensive rats and those from their normotensive controls. Both isolated membranes (erythrocyte ghosts) and whole cells (platelets) were studied.

2. In the Okamoto-Aoki strain, the fluorescence polarization of diphenylhexatriene and consequently the ‘equivalent microviscosities' were altered in all membranes, even in those of young normotensive SHR. These abnormalities varied with age (in whole cells) and were not detected in females.

3. These alterations were not restricted to the SHR strain and were also observed in the Sabra hypertensive strain (SBH). The ‘equivalent microviscosity’ of hypertensive Sabra erythrocyte ghosts was higher than that of the original Sabra rats. Salt loading of the Sabra rats promoted an increase in the ‘equivalent microviscosity’ of their erythrocyte membranes, which nearly reached the Sabra hypertensive level.

4. These results support the hypothesis of a genetic change in hypertensive rats leading, directly or indirectly, to diffuse alterations of cell membrane structure, which seem to be similar to those caused by high salt intake.
Augmentation of Prostaglandin Production by Linoleic Acid in Man
Authors: Epstein Murray , Lifschitz Meyer , Rappaport Kenneth
Published: August 2015

1. Since several lines of evidence have suggested that a diminution of endogenous prostaglandins (PG) may participate in the pathogenesis of a variety of disease states, it would be advantageous to develop therapeutic approaches that augment endogenous prostaglandin synthesis. Since linoleic acid is readily converted to arachidonic acid, we assessed the effects of linoleic acid administration on immunoassayable PGE and 6-oxo-PGF1α excretion as indices of PGE2 and PGI2 production.

2. Six normal subjects were studied twice: during a seated control study and during an 8 h infusion of a 10% emulsion of safflower oil (Liposyn) containing approx. 77% linoleic acid, in a dose of 1·5 g/kg body weight.

3. Liposyn induced a profound increase in immunoassayable 6-oxo-PGF1α excretion.

4. Simultaneously, immunoassayable PGE excretion increased modestly.

5. The current study raises the possibility that linoleic acid administration might constitute a new therapeutic approach in managing disorders characterized by an impairment of the ability to augment prostaglandin synthesis.
Erythrocyte Membrane Transport Systems as Possible Markers for Essential Hypertension
Authors: Barlassina D. Cusi. C. , Ferrandi M. , Brevi R. , Vazzola A. , Bianchi G.
Published: August 2015

1. Erythrocyte Na+-K+ cotransport and Na+-Li+ countertransport were measured at the same time in 56 essential hypertensive patients, 24 of their normotensive offspring and 36 matched normotensive controls.

2. The mean value of Na+-K+ cotransport is slower and of Na+-Li+ countertransport is faster in the essential hypertensive group and in some of their normotensive offspring, but a great overlap with the value of the normotensive group was observed.

3. Na+-K+ cotransport values were bimodally distributed in the hypertensive group, with the first mode at 250 and the second at 600 μmol h−1 l−1 of erythrocytes.

4. The ratio Na+-K+ cotransport/Na+-Li+ countertransport was calculated. It was found that such a ratio distinguishes between normotensive and essential hypertensive subjects better than the individual transport systems alone.
Increased Vascular Sensitivity to Serotonin and Methysergide in Hypertension in Rats
Authors: Webb R. Clinton
Published: August 2015

1. The effect of the hypertensive process on vascular sensitivity to serotonin and methysergide was studied.

2. Isometric contractions were recorded from arteries isolated from spontaneously hypertensive (SHR), Kyoto-Wistar normotensive (WKY), deoxycorticosterone acetate (DOCA)-hypertensive and Sprague-Dawley normotensive rats.

3. Arteries from hypertensive rats (except SHR aorta) were more sensitive (lower ED30) to noradrenaline, serotonin and methysergide relative to those from controls.

4. The magnitude of the leftward shift in ED30 was similar for the three agonists in mesenteric and tail arteries from DOCA rats, whereas the shift in ED30 for serotonin and methylsergide in aortae exceeded that to noradrenaline. In SHR, the shift in ED30 for serotonin and methylsergide in tail and mesenteric arteries was greater than that to noradrenaline; SHR aortae did not differ from WKY aortae.

5. Arteries from hypertensive rats (except SHR aorta) developed a greater maximal contraction to methysergide than those from controls; maximal contractions to noradrenaline and serotonin were either less than or similar to those of controls.

6. The agonistic action of methysergide in DOCA rats paralleled the development of high arterial pressure. Low sodium diet abated the high pressure in DOCA rats and reduced vascular sensitivity to all agonists.

7. These observations support the view that in hypertension there is a generalized increase in vasoconstrictor sensitivity. The major finding is that, in two hypertensive models, there is a uniquely greater increase in vascular responsiveness to the agonistic action of methysergide.
Glucocorticoid Hypersecretion and Hypertensive Vascular Disease in Experimental Malignant Hypertension in Rats
Authors: Chatelain R. E. , Bumpus F. M. , Dibello P. M. , Ferrario C. M.
Published: August 2015

1. Changes in plasma glucocorticoid levels and the alterations they imposed upon the lymphoid system and vascular hypertrophy were studied in rats developing either the benign or malignant forms of hypertension during the initial 30 days after aortic ligation.

2. A threefold increase in plasma corticosterone was observed during both the acute and chronic phases of malignant hypertension, whereas in benign hypertension, after a short-lasting twofold increase, corticosterone returned to normal within 9 days.

3. Thymus atrophy, thymocyte depletion and impaired thymocyte reactivity characterized the acute phase of benign and malignant hypertension. After 9 days these alterations receded in benign hypertension, whereas they were permanent features accompanied by severe lymphocytopenia and marked neutrophilia in malignant hypertension.

4. Syntheses and contents of collagen and elastin were impaired in the arteries of malignant hypertensive rats. In contrast, elevated synthesis and increased deposition of these proteins were observed in benign hypertensive rats. Both forms of the disease were characterized by increased deposition of arterial non-fibrous protein.

5. Although acute arterial fibrinoid deposition was observed in benign and malignant hypertension, fibrinoid disappeared in benign hypertensive rats whereas it evolved into necrotizing lesions characterized by disruption of the arterial structure and lymphoid cell infiltration in malignant hypertensive rats.

6. These studies indicate that differing patterns of altered glucocorticoid secretion accompany the development of benign and malignant hypertension. These hormones, by altering the lymphoid system and arterial connective tissue metabolism may participate in the development and perpetuation of the necrotizing arterial lesions observed in malignant hypertension.
Outpatient Screening Procedures for Primary Aldosteronism
Authors: Streeten David H. P. , Anderson Gunnar H. , Springer Jay M.
Published: August 2015

1. The sensitivity and specificity of several individual and combined measurements for the diagnosis of primary aldosteronism have been calculated in 22 patients with established primary aldosteronism and 140 essential hypertensive controls.

2. Excellent sensitivity and specificity (93-100%) in the diagnosis of primary aldosteronism cannot be accomplished with any single test but can be achieved with combinations of (a) a low ‘stimulated’ plasma renin activity (PRA) (after frusemide and orthostasis) together with either hypokalaemia or a high ‘stimulated’ plasma aldosterone concentration (above 944 pmol/l), or (b) a low ‘stimulated’ PRA, together with either hypokalaemia or a high saline-suppressed plasma aldosterone concentration (above 236 pmol/l), or (c) a pressor response to saralasin together with elevated values of NaCl-suppressed or frusemide-stimulated plasma aldosterone concentration. Procedures (a) or (c) can be completed in 3–4 h; (b) requires 8 h.
Regional Distribution of Angiotensinogen in the Central Nervous System of the Rat: Effect of DOC-Salt Treatment
Authors: Basso Nidia , Grispon Diana , Ruiz Patricia , Taquini Alberto C.
Published: August 2015

1. The distribution of angiotensinogen and endogenous renin-like activity were analysed in different areas of the central nervous system in normal and DOC-salt-treated hypertensive rats.

2. Angiotensinogen concentration and renin-like activity were significantly increased in the cerebral cortex, cerebellum, hypothalamus and brain stem of the DOC-salt-treated rats 30 days after the initiation of the experiment.

3. Influence of plasma contamination on the former results was evaluated by the determination of (a) plasma angiotensinogen concentration in control and treated animals and (b) blood content remaining in the different regions of the central nervous system, after saline perfusion of the brain, in a group of normal rats.

4. Plasma angiotensinogen concentration was significantly decreased in DOC-salt-treated rats, therefore blood contamination would tend to diminish the magnitude of increase in central nervous system angiotensinogen in these animals.

5. Present results have shown an increased concentration of angiotensinogen in some areas of the central nervous system in DOC-salt-treated rats. The results have also confirmed an enhanced activity of the endogenous renin-like enzyme in the same regions; this change seems to be mainly due to the increment in angiotensinogen. Increased formation of central angiotensin could be involved in the development of DOC-salt hypertension. The biosynthetic pathways of renin substrate as well as its endogenous regulation remain undetermined.
Changes in Blood Pressure in Relation to Vascular and Plasma Renin after Renin Injection in Rats
Authors: Loudon M. , Bing R. F. , Swales J. D. , Thurston H.
Published: August 2015

1. To assess the relative importance of vascular as opposed to plasma renin, groups of conscious rats received a single intravenous injection of partially purified rat renin 18 h after bilateral nephrectomy. Blood pressure was monitored continuously and plasma and aortic renin concentrations were determined at 1, 3, 6 or 9 h after injection. In separate groups of rats the effect of the competitive angiotensin II antagonist, saralasin, on blood pressure was measured 3 or 6 h after renin injection.

2. Blood pressure remained elevated for up to 6 h after renin injection, returning to normal by 9 h. Saralasin infusion reversed the rise in blood pressure at both 3 and 6 h after injection.

3. Aortic renin concentration followed the pattern of the pressor response whereas plasma renin concentration had returned to subnormal values by 3 h.

4. Circulating renin of renal origin is taken up by aortic tissue. The pressor response to exogenous renin in rats after bilateral nephrectomy is not related to changes in plasma renin but is similar in duration to the persistence of aortic renin-like activity and can be blocked by saralasin at both 3 and 6 h after injection.
Release and Extraction of Pressor Hormones by the Human Hypertensive Kidney
Authors: De Leeuw P. W. , Punt R. , Van Soest G. A. , Tchang P. , Birkenhäger W. H.
Published: August 2015

1. In 11 patients with uncomplicated essential hypertension in whom renal arteriography had been carried out, arterial and venous samples were drawn for determination of active renin, angiotensin II and catecholamines, both before and after 3 min of static exercise (handgrip).

2. In five patients the experiment was continued by administration of phentolamine (5 μg min−1 kg−1) into the renal artery. During this procedure blood samples were drawn again before and after handgrip exercise. At all times renal plasma flow was measured from the clearance and extraction of [125I]hippuran.

3. At rest the kidney secreted renin and noradrenaline, and angiotensin II and adrenaline were extracted from the circulation. During static exercise secretion of renin and noradrenaline was enhanced, and extraction efficiency for angiotensin II and adrenaline was reduced. During infusion of phentolamine similar patterns were found for renin and catecholamines, but the pattern for angiotensin II was reversed.

4. It is concluded that sympathetic activity in the kidney and perhaps also the absolute level of renal blood flow determine the renal extraction efficiency for angiotensin II. Reduced uptake of angiotensin II by an α-adrenergic mechanism may protect the kidney from excessive vasoconstriction.
Significance of the Brain Renin—Angiotensin System in Spontaneously Hypertensive Rats
Authors: Tonnaer Jeroen A. D. M. , van Put Joke J. , Wiegant Victor M. , de Jong Wybren
Published: August 2015

1. The renin inhibitor N-acetyl-pepstatin was infused for 14 days or 5 days into the cerebral ventricular system of young and adult spontaneously hypertensive rats respectively.

2. The blood pressure and heart rate of the young animals was significantly lower as a result of this treatment, whereas the pressure of the adult animals tended to decrease.

3. The mechanism involved in the hypotensive effect of N-acetyl-pepstatin appeared to be independent of the peripheral renin-angiotensin system. The possible involvement of a decreased sympathetic outflow is suggested.

4. The present data indicate that the brain renin-angiotensin system contributes to the development of hypertension in the spontaneously hypertensive rat.
Reversible Acid-Activation of Inactive Renin: Evidence Favouring a Unimolecular Reaction
Authors: Atlas Steven A. , Hesson Thomas E. , Sealey Jean E. , Laragh John H.
Published: August 2015

1. Purified inactive renin from human kidney or plasma was activated to a similar extent by incubation with trypsin or by dialysis to pH 3.3.

2. Trypsin- or acid-activated inactive renin was like active renal renin in terms of pH optimum (pH 5.5-6.0) and inhibition by mono-specific antibody. The apparent Km of homologous angiotensinogen for acid-activated inactive renin (1.11 μmol/l) was the same as for trypsin-activated inactive renin (1.12 μmol/l) or active renal renin (1.07 μmol/l).

3. In contrast with trypsin-activated renin, acid-activated renin was reversibly inactivated in a time-dependent manner during incubation at 37°C above pH 5. The maximal rate of reversal occurred in the pH 7–8 range. Reversal was prevented by prior incubation with trypsin, plasmin, glandular kallikrein or plasma kallikrein.

4. By kinetic analysis, the reversal of activation was found to be a first-order decay process with a reaction half-time (7–8 min at 37°C, pH 7.4) that was independent of the initial concentration of activated enzyme.

5. These results indicate that reversible acid-activation of inactive renin is a unimolecular reaction, consistent with the hypothesis that acid pH induces a conformational change in a single polypeptide chain.
Antibody-Sensitive Renin of Adrenal and Resistance Vessels is Markedly Elevated in Spontaneously Hypertensive Rats
Authors: Naruse Mitsuhide , Inagami Tadashi
Published: August 2015

1. Three-week-old spontaneously hypertensive rats (SHR) showed markedly elevated specific renin activity in the adrenal and the mesenteric vessels compared with control Wistar-Kyoto (WKY)rats.

2. In 17-week-old SHR with established hypertension, adrenal renin remained markedly elevated over that of WKY rats, whereas no significant difference was observed in renin of the mesenteric vessels.

3. The specific renin activity of the aorta showed no significant difference compared with that of WKY rats at 3 or 17 weeks of age.

4. These results suggest possible involvement of adrenal and vascular renin in the pathogenesis of hypertension in SHR.
Proximal and Distal Tubular Reabsorption during Isotonic Volume Expansion in Patients with Essential Hypertension as Estimated by Means of Combined Lithium and 51Cr-Labelled EDTA Clearance
Authors: Holstein-Rathlou N.-H. , Svendsen U. G. , Leyssac P. P.
Published: August 2015

1. Ten patients with essential hypertension and ten normotensive control subjects were investigated before and after an isotonic volume load.

2. The increases in the clearances of lithium and of sodium were greater in the hypertensive than in the normotensive subjects (P < 0.05). The fractional increases showed a positive correlation (rs = 0.68, P < 0.05) in the hypertensive patients.

3. An increase in glomerular filtration rate in the hypertensive patients correlated positively with the increase in proximal output (rs = 0.70, P < 0.05), but did not correlate with the change in sodium excretion.

4. The exaggerated natriuresis was accompanied by a significant rise in the absolute rate of sodium reabsorption in the distal segments, but distal fractional reabsorption decreased.

5. It is concluded that the exaggerated natriuresis can be accounted for by an increase in the proximal output of sodium and water.
Total Nephrectomy Alters Circulating Humoral Agents in Salt-Fed, Low-Renin Dahl S Rats to Favour Reduced Vasoconstriction in an Isolated, Perfused Bioassay Hindquarters
Authors: Tobian Louis , Johnson-Hanlon Susan , Zitur Mary , Iwai Junichi
Published: August 2015

1. When all renal tissue is removed from salt-fed Dahl S rats, the excessive amounts of a circulating humoral vasoconstrictor effect (or lack of a vasodilator effect) are abolished, and Dahl S rats become the equal of Dahl R rats with regard to these circulating vasoconstrictor effects.

2. Total nephrectomy of salt-fed S rats also alters circulating humoral agents so that vasoconstrictor responses to sympathetic nerve stimulation and to noradrenaline infusions are markedly diminished in a perfused hindquarters preparation.

3. Both these effects of total nephrectomy are seen only in S rats, not in R rats, although plasma renin levels are lower in S rats. Thus total nephrectomy must remove much more renin and angiotensin II in R rats.

4. The effect of total nephrectomy in S rats need not necessarily be the direct removal of circulating vasoconstrictor humoral agents issuing from the S kidney. It is quite possible that removal of S kidneys has a strong influence upon the release of circulating vasconstrictor or vasodilator agents emerging from other parts of the body.

6. These effects of total nephrectomy occurring solely in S rats add still more evidence pointing to a pivotal role for the kidney in the mechanism of the NaCl hypertension of Dahl S rats.
Arachidonic Acid Stimulates Renal Kallikrein Release in Isolated Rat Kidney
Authors: Vio Carlos P. , Churchill Laurie , Terragno Alicia , McGiff John C. , Terragno Norberto A.
Published: August 2015

1. The effect of arachidonic acid on kallikrein release was studied in an isolated rat kidney perfused with a modified Krebs-Henseleit solution.

2. Kallikrein activity was measured in both venous and urinary effluents, after DEAE-Sephadex chromatography with D-Val-Leu-Arg-p-nitroanilide as a substrate.

3. Arachidonic acid (AA) (30 nmol/ml) induced a threefold increase in kallikrein activity in the venous effluent (control = 131 ± 9 kallikrein amidase μ-units/ml vs AA = 411 ±49 kallikrein amidase μ-units/ml, P < 0.005).

4. The stimulatory effect of arachidonic acid on kallikrein release is mediated by prostaglandins, since it can be prevented by the addition of indomethacin (1 μg/ml).

5. Our results demonstrate that kallikrein is released by the perfused kidney into the renal venous effluent, and that this release can be hormonally regulated by a mechanism involving prostaglandin synthesis.
Effect of Pharmacological Inhibition of Renin, Prostaglandin and Kallikrein Systems on Surgical Correction of Longstanding Two-Kidney, One-Clip Hypertension in the Rat
Authors: Russell G. I. , Bing R. F. , Swales J. D. , Thurston H.
Published: August 2015

1. Longstanding two-kidney, one-clip hypertension in the rat was rapidly reversed by removal of the constricting clip and the reversal, was complete by 12 h.

2. Blood pressure was lowered by renin-angiotensin inhibition, caused by saralasin or captopril, but not to normotensive levels. Infusion with indomethacin or aprotinin over a 15 h period did not affect the blood pressure.

3. The pattern of fall in blood pressure after removal of the clip was similar when rats were infused with saralasin, captopril, indomethacin or aprotinin. Blood pressure was normal at 24 h and did not differ significantly from that of unclipped rats given an infusion of glucose.

4. The fall in blood pressure produced by unclipping was not altered by inhibition of the renin-angiotensin system and did not appear to be mediated via the prostaglandin or kallikrein systems.