bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Noise on Blood Pressure and ‘Stress’ Hormones
Authors: Andrén L. , Lindstedt G. , Björkman M. , Borg K. O. , Hansson L.
Published: August 2015

1. Noise stimulation (95 dBA) for 20 min caused a significant increase in diastolic (12%, P < 0.001) and mean arterial pressure (7%, P < 0.001) in 15 healthy normotensive male subjects.

2. There was no significant change in systolic blood pressure or heart rate during exposure to noise.

3. Adrenaline, noradrenaline, prolactin, cortisol and growth hormone concentrations in venous plasma were not affected during noise stimulation.
Sulphydryl Oxidation in the Mechanism of Molecular-Weight Conversion of Renin in Dog Kidney
Authors: Ikemoto Fumihiko , Takaori Kazuo , Iwao Hiroshi , Yamamoto Kenjiro
Published: August 2015

1. A high-molecular-weight renin (Mr 60 000) was formed by the reaction of a low-molecular-weight renin (Mr 40 000) with a renin-binding substance in canine renal cortical extract in the presence of the sulphydryl (SH) group oxidizing agent potassium tetrathionate; thus the reaction required SH oxidation.

2. Renin extracted from isolated renin granules was adsorbed on to thiopropyl Sepharose 6B, and then liberated with dithiothreitol (50 mmol/l), indicating that it possessed on SH moiety(s).

3. However, the renin was capable of reaction with the renin-binding substance even after its SH moiety (or moieties) was protected with 5,5′-dithiobis-(2-nitrobenzoic acid).

4. The high-molecular-weight renin was converted into the low-molecular-weight renin by incubation (37°C, 15 min) with cytosol (soluble fraction) of renal cortex and liver. Such converting ability was diminished after the cytosol was treated with perchloric acid or potassium tetrathionate.

5. These results suggest that the reaction of renin with the renin-binding substance does not require disulphide bond(s) and that an enzymelike substance which is sensitive to SH oxidation is involved in the conversion from the high-molecular-weight renin into the low-molecular weight renin.
Diagnostic Enzymology of a-L-Iduronidase with Special Reference to a Sulphated Disaccharide Derived from Heparin
Authors: Hopwood J. J. , Muller Vivienne
Published: August 2015

1. Iduronosyl anhydro[1-3H]mannitol 6-sulphate (IMs), iduronosyl anhydro[1-3H]mannitol, phenyl iduronide (PhI) and 4-methylumbelliferyl iduronide have been compared as substrates for the diagnostic estimation of α-l-iduronidase activity present in human leucocyte and cultured skin fibroblast homogenates. The pH profile of leucocyte and fibroblast iduronidase activity was dependent on substrate structure and concentration, the ionic strength and the nature of the buffer ion used in the assay mixture.

2. NaCl, KBr and Na2SO4 were shown to be parabolic competitive inhibitors of IMs activity, the K1 with fibroblast homogenates being 34, 13.4 and 0.22 mmol/l respectively. NaCl and KBr were shown to have a primary salt effect on the interaction between enzyme and substrate but Na2SO4 appeared to have a specific ion effect at a cationic binding site.

3. NaCl inhibited the hydrolysis of IMs at all pH values studied, whereas NaCl concentrations of 0.2 mol/l inhibited the hydrolysis of PhI at pH values below 3.8 but activated the enzyme at higher incubation pH values.

4. Cu2+ was shown to be a potent non-competitive inhibitor of IMs enzyme activity with an apparent Kl, of approximately 0.02 mmol/l. The enzyme activity was inhibited by Fe2+ (Kl 4 mmol/l), Hg2+ and Ag+, but has not significantly been affected by other univalent or bivalent cations.

5. The presence of solvent and salt effects on apparent Km but not the Vmax. suggest that the binding of IMs to the enzyme involved charge neutralization, and it is inferred that two cationic binding sites are present at the active site. It is postulated that one site specifically binds to the iduronic acid carboxyl group, the other to the 6-sulphate of the anhydromannitol moiety.
Factors Influencing Hepatic Glutathione Concentrations: A Study in Surgical Patients
Authors: Shi E. C. P. , Fisher R. , McEvoy Maeve , Vantol Rebecca , Rose Margaret , Ham J. M.
Published: August 2015

1. Hepatic total glutathione (reduced plus oxidized) and oxidized glutathione levels were measured in operative wedge liver biopsy specimens obtained from 70 patients.

2. The effects on hepatic reduced glutathione (GSH) level of four potential risk factors (abnormal liver histology, abnormal preoperative tests of liver function, drug ingestion and protein malnutrition) were examined.

3. Each of the four risk factors was associated with a significant reduction in hepatic GSH. Multivariate analysis indicated that only three of these risk factors (abnormal liver histology, drug ingestion and protein malnutrition) had independent effects in reducing hepatic GSH.

4. Twenty-five of the 70 patients studied did not have any of the four risk factors. The mean hepatic GSH level in these patients was 3.92 μmol/g of liver wet weight (sd 0.62), giving a 95% reference range of 2.71–5.14 μmol/g of liver wet weight.
Effect of Changes in Sodium Balance on Potassium/Aldosterone Dose-Response Curves in the Dog
Authors: Nicholls M. G. , Tree M. , Livesey J. H. , Fraser R. , Morton J. J. , Robertson J. I. S.
Published: August 2015

1. Potassium was infused intravenously in an incremental fashion and the plasma aldosterone responses were measured in conscious beagle dogs at five different intakes of dietary sodium.

2. Potassium/aldosterone dose—response curves were constructed for each dietary sodium regimen.

3. The rate of increase of plasma potassium during graded potassium infusion became progressively greater with increasing sodium depletion.

4. Regression lines of plasma aldosterone on plasma potassium were progressively elevated and steepened with increasing sodium depletion.

5. The alteration of these dose-response curves could in part have been the result of chronic elevation of plasma potassium and angiotensin II, and depression of plasma sodium, with sodium deprivation.

6. By contrast, acute changes in plasma angiotensin II or sodium concentrations across incremental infusions of potassium did not explain the progressive changes in the potassium/aldosterone dose—response curves.

7. The steepest part of the plasma aldosterone response curve was in the plasma potassium range 4–6 mmol/l.

8. Maximum achieved aldosterone levels were similar to or greater than those attained during angiotensin II infusion in previous studies in beagle dogs.

9. Potassium, like angiotensin II and adrenocorticotropic hormone, becomes a more effective stimulus to aldosterone with sodium depletion, thereby facilitating the preservation of sodium homoeostasis.
A Biochemical and Immunological Investigation into the Physiological Basis of the Increased Albumin Filtration Induced in Hyperalbuminaemic Female Wistar Rats
Authors: Lawrence Gillian M. , Brewer D. B.
Published: August 2015

1. The level of proteinuria induced in female Wistar rats after bovine albumin injection intraperitoneally was highly dose dependent.

2. The proteinuria remained highly selective, with albumin constituting approximately 90% of the total protein excreted, even in the most severely affected rats.

3. Calculations relating the amount of bovine albumin available in the serum for filtration to the amount excreted in the urine indicated that complete saturation of the reticuloendothelial and tubular protein reabsorption systems-5-have occurred during the course of the 5 day injection period in rats given more than 3.5 mg of bovine albumin day−1 g−1 body wt.

4. When this situation was attained there appeared to be no further increase in glomerular permeability to either rat or bovine albumin and an equilibrium state seemed to exist where, when serum albumin levels were raised above the normal level, all the excess albumin passed across the glomerular filter to be excreted in the urine.

5. The passage of these large quantities of albumin across the glomerular filter-5-have resulted not from ultrastructural damage to the filter itself but rather from the generation of vastly increased concentration gradients across the glomerular basement membrane, which were sufficiently large to overcome the electrostatic repulsive forces which normally severely restrict albumin filtration.
Inhibitory Activity of Human Urine on Calcium Oxalate Crystal Growth: Effects of Sodium Urate and Uric Acid
Authors: Fellström B. , Backman U. , Danielson B. G. , Holmgren K. , Ljunghall S. , WikströM B.
Published: August 2015

1. Freshly voided urine from healthy subjects was pooled and ultrafiltered (10 000 daltons). The ultrafiltrable and the macromolecular portions were preincubated with calcium oxalate, uric acid and sodium urate crystals and the effects on the inhibitory activity of calcium oxalate crystal growth assessed by monitoring the disappearance of [14C]oxalate from the solution.

2. The inhibitory activity of the ultrafiltrate was higher than that of the urinary macro-molecular fraction. Both uninhibited and inhibited crystal growth processes followed second-order kinetics.

3. Calcium oxalate crystals adsorbed almost all the urinary macromolecular inhibitors whereas sodium urate or uric acid crystals adsorbed only 10–20%.

4. In the presence of a metastable solution of calcium oxalate, the incubation of the urinary macromolecular fraction with sodium urate crystals caused a pronounced reduction in the inhibitory activity. A similar effect was seen with uric acid crystals, but to a lesser degree.

5. We conclude that the effect of sodium urate or uric acid crystals alone on naturally occurring urinary macromolecular inhibitors of calcium oxalate crystal growth is weak, but that in the presence of metastable calcium oxalate this is greatly enhanced. A substantial adsorption of the inhibitors on to the crystals is suggested, possibly secondary to epitaxial growth of calcium oxalate on the surface of the urate crystals.
Maximal Biliary Secretion of Bilirubin in the Anaesthetized Rat: Dependence on UDP-glucuronosyltransferase Activity
Authors: Van Steenbergen W. , Fevery J.
Published: August 2015

1. Hepatic bilirubin UDP-glucuronosyl transferase activity in heterozygous Gunn rats (Jj) was only two-thirds of that in the parent Wistar rats (JJ). The former excreted only 30% of their bilirubin conjugates into bile as diglucuronide in contrast to 48% in the Wistar rats. As similar changes have been observed in Gilbert's syndrome, heterozygous Gunn rats can be used as a model for this disorder.

2. Treatment for 2 weeks with phenobarbitone or glutethimide produced a 2.6- and a 1.3-fold increase in hepatic glucuronosyltransferase activity in Wistar and heterozygous Gunn rats respectively. Bilirubin apparent maximal biliary secretory capacity (Tm) was enhanced in all animals pretreated with the enzyme inducing agents. A relationship was found between the transferase activity and the Tm value. At low transferase activities (Jj rats) a small increase in enzyme activity was accompanied by a marked enhancement of the Tm; at higher enzyme activities (Wistar rats) the increase in Tm. was less pronounced. These data suggest that the maximal biliary secretion of bilirubin is dependent on conjugation capacity, and that the currently used assay of the digitonin-activiated glucuronosyltransferase yields physiologically meaningful data.

3. In general, bilirubin diglucuronide excretion in bile increased in parallel with higher hepatic glucuronosyltransferase activities, as previously documented in man. However, this relationship was not present in glutethimide-pretreated animals. A high bilirubin load decreased the diglucuronide output in heterozygous Gunn rats. These observations demonstrate that the ratio of mono- to di-glucuronide in bile is mainly but not solely determined by the transferase activity.
Urea, Glucose and Alanine Kinetics in Man: Effects of Glucose Infusion
Authors: Royle G. T. , Molnar J. A. , Wolfe Marta H. , Wolfe R. R. , Burke J. F.
Published: August 2015

1. The simultaneous effects of an intravenous glucose infusion on plasma urea, glucose and alanine kinetics were investigated in normal post-absorptive man.

2. The primed constant intravenous infusion of compounds labelled with stable isotopes, [15N2]urea, [6-2H]glucose and [3-13C]alanine, was used.

3. The rate of appearance of glucose and urea in the plasma was rapidly reduced by the 17.7 μUmol min−1 kg−1 glucose infusion.

4. In contrast, during the glucose infusion there was an increased rate of appearance of alanine in the plasma, and an increased percentage of glucose carbon atoms derived from alanine.

5. Reduced production of glucose and urea during the glucose infusion was not due to decreased gluconeogenesis from alanine.
Tubular Function in Glycerol Induced Acute Renal Failure in Rats: Effect of Saline Loading and Prior Acute Renal Failure
Authors: Westenfelder C. , Crawford P. A. , Hamburger R. K. , Baranowski R. L. , Kurtzman N. A.
Published: August 2015

1. Chronic saline loading and prior induction of acute renal failure are manoeuvres which have been reported to protect against the development of acute renal failure. The underlying mechanisms are unclear. The purpose of the present study was to examine the effect of these protective manoeuvres on glomerular filtration rate (GFR) and proximal and distal tubular function in the glycerol-induced model of acute renal failure.

2. Acute renal failure was induced (50% glycerol, 10 ml/kg body wt. intramuscularly) in three groups of rats: group 1, water drinking; group 2, saline loaded (1% NaCl as drinking fluid for 5 weeks); group 3, rechallenged 7–15 days after a first dose of glycerol, when blood urea nitrogen levels had returned to normal. Control animals in group 3 received only the first glycerol injection, then, like the controls in groups 1 and 2, they were given 0.9% NaCl solution (10 ml/kg body wt. intramuscularly). All animals were then studied 24 h after glycerol or saline injection.

3. Glycerol caused a significant fall in GFR in all three groups (78% group 1; 64% group 2; 59% group 3); blood urea nitrogen levels rose significantly. Saline-loaded animals with acute renal failure (group 2) exhibited glycosuria with normal blood-sugar levels and a striking depression in maximal tubular glucose reabsorption. The capacity to reabsorb HCO−3 was depressed both before and during HCO−3 loading. Distal acidification as assessed by the urine to blood gradient of Pco2 (U—B Pco2) was normal during HCO−3 loading (urine pH 7.8). The presence of hyperchloraemic metabolic acidosis demonstrated that these animals developed proximal renal tubular acidosis. Glycerol-reinjected rats with acute renal failure (group 3) reabsorbed glucose and HCO−3 normally and exhibited normal distal tubule acidification.

4. We conclude from these data that a prior episode of acute renal failure protects proximal tubules against a second glycerol challenge, whereas chronic saline loading is without this protective effect. Both the underlying mechanism for this tubular cell resistance (against a second glycerol challenge) and the role of proximal tubular function in the pathogenesis of acute renal failure remain unclear.
Evidence of Altered Structure of the Erythrocyte Membrane in Spontaneously Hypertensive Rats
Authors: Orlov S. N. , Gulak P. V. , Litvinov I. S. , Postnov YU. V.
Published: August 2015

1. The membrane structure of erythrocytes of rats with different forms of arterial hypertension was studied by means of two hydrophobic fluorescent probes (diphenylhexatriene and pyrene).

2. Microviscosity of hydrophobic areas of erythrocyte membrane of spontaneously hypertensive rats was found to be increased compared with that of membranes from normotensive control rats.

3. No alterations of membrane structure of erythrocytes of deoxycorticosterone-treated rats and renal hypertensive rats were found.
Influence of Respiratory Heat Transfer on Thermogenesis and Heat Storage after Cold Immersion
Authors: Morrison J. B. , Conn M. L. , Hayes P. A.
Published: August 2015

1. Ten male subjects were cooled on three occasions to a rectal temperature of 35°C by immersion to the neck in water at 11·3°C. The subjects were rewarmed for 60 min, once by metabolic heat production alone (shivering), once by inhalation rewarming with spontaneous breathing of saturated air at 47°C (control) and once by inhalation rewarming with ventilation regulated at 40 litres/min by respiring a controlled fraction of CO2 (hyperventilation).

2. Metabolic heat production was substantially reduced by inhalation rewarming (P < 0·05), from 913 kJ when shivering to 766 kJ (control) and 613 kJ when hyperventilating. The fall in metabolic heat production was greater than the corresponding respiratory heat gain, which increased from a loss of 41 kJ when shivering to gains of 85 kJ (control) and 169 kJ (hyperventilation).

3. As differences in mean skin temperatures were small (<1·0°C), it is concluded that the lower metabolic heat production in response to increased respiratory heat input must result from more rapid central temperature gains. This conclusion is supported by the relative values of rectal and tympanic temperatures. It was calculated that the percentage of the total heat supply which was donated to the core increased from 13% during shivering to 16% for the control and 23% in hyperventilation. Results imply that respiratory heat input is more efficient than metabolic heat production in elevating central temperature.
An Estimate of the Endogenous Secretion Rate of Calcitonin in Man
Authors: Kanis J. A. , Heynen G. , Cundy T. , Cornet F. , Paterson A. , Russell R. G. G.
Published: August 2015

1. The metabolic clearance rate (MCR) of human calcitonin was measured in 12 normal subjects and four patients with Paget's disease by the infusion of synthetic human calcitonin (15–40 μg/h for 2–24 h), and in 10 additional patients with Paget's disease from the disappearance rate of immunoreactive calcitonin from plasma after the intravenous injection of large doses of synthetic human calcitonin (0·5–1·0 mg).

2. The estimated MCR during the infusion studies (range 531–1224 litres/day) was similar to that calculated from the disappearance of large doses of synthetic human calcitonin injected intravenously in patients with Paget's disease (mean = 1035 litres/day; range = 593–1408 litres/day).

3. An eightfold range in the basal values of plasma immunoreactive calcitonin, in spite of the presence of a relatively constant MCR, suggests that the variation in basal plasma calcitonin was due principally to variation in the endogenous secretion rate for calcitonin.

4. The results suggest that the endogenous secretion rate for calcitonin is low in normal subjects (mean 124 ± sem 24 μg/day), and give a basis for selecting the doses of calcitonin which can be considered physiological.
Interpretation of Tracer Studies on Plasma Protein Turnover: Comparison of Methods and Optimization of Techniques
Authors: Reeve J. , Pussell B. , Gibbs G. P. , Peters D. K.
Published: August 2015

1. A comparison of several published methods for analysing plasma protein turnover data has been undertaken, with particular reference to rapidly metabolized proteins such as members of the complement series.

2. With the exception of the equilibrium time method, most methods proved adequate for the determination of overall fractional catabolic rates. A further exception is that the renal clearance method becomes invalid when the fractional catabolic rate approaches the renal iodide clearance, but this may be the method of choice for slowly metabolized proteins if accurate urine collections can be ensured.

3. For the measurement of the ratio of extra-to intra-vascular protein pool size a clear preference emerged for the method of C. M. E. Matthews (1957, Physics in Medicine and Biology, 2, 36–53). For rapidly metabolized proteins the calculations must be preceded by a correction for the non-protein bound iodide retained in the intra- and extra-vascular spaces.

4. The accurate calculation of fractional catabolic rate in the extravascular pool generally requires more experimental data than are commonly collected as well as an accurate correction for non-protein bound label that remains unexcreted. Only two techniques hold promise of accurate results: Nosslin's rate equations method and a development of Vitek's deconvolution method described herein. Nosslin's integrated rate equations method is particularly affected by systematic errors in renal iodide clearance estimates and should probably not be further used for this purpose.
Relation of Arterial Pressure with Body Sodium, Body Potassium and Plasma Potassium in Essential Hypertension
Authors: Beretta-Piccoli C. , Davies D. L. , Boddy K. , Brown J. J. , Cumming A. M. M. , East B. W. , Fraser R. , Lever A. F. , Padfield P. L. , Semple P. F. , Robertson J. I. S. , Weidmann P. , Williams E. D.
Published: August 2015

1. Exchangeable sodium (NaE), plasma electrolytes and arterial pressure were measured in 121 normal subjects and 91 patients with untreated essential hypertension (diastolic >100 mmHg), 21 of whom had low-renin hypertension. Plasma concentrations of renin, angiotensin II and aldosterone were measured in all hypertensive patients, total body sodium, total body potassium and exchangeable potassium (KE) in some patients.

2. Mean NaE was not different in normal and hypertensive subjects provided the two groups were matched for leanness index. In the subgroup of young hypertensive patients aged 35 years or less mean NaE was below normal. NaE was not related to arterial pressure in normal subjects but in hypertensive patients there were positive and significant correlations of arterial pressure with NaE and with total body sodium.

3. NaE and total body sodium increased with age in hypertensive but not in normal subjects. Partial regression analysis suggested that the correlation of NaE with arterial pressure was not explained by an influence of age.

4. Mean NaE was not increased and mean KE was not decreased in patients with low-renin hypertension.

5. Plasma potassium concentration, KE and total body potassium correlated inversely and significantly with blood pressure in hypertensive patients. These correlations were more marked in young than in old patients.

6. Multiple regression analysis showed that the combination of NaE and plasma potassium concentration ‘explained’ more of the variation of systolic blood pressure in hypertensive patients than it did in normal subjects. Plasma potassium concentration ‘explained’ more of the variation in young hypertensives and NaE ‘explained’ more in older patients.

7. Our findings suggest that changes of plasma and body potassium are important in the earlier stages of essential hypertension and that changes of body sodium become important later.
Mechanism of Pressor Effects of Intraventricular Injection of Angiotensin II in the Rat: Role of Vasopressin and Renal Nerves
Authors: Suzuki Hiromichi , Kondo Kazuoki , Handa Michiko , Kawabe Hiroshi , Saruta Takao
Published: August 2015

1. The role of the kidney and vasopressin in the increase of blood pressure obtained when angiotensin II is injected intraventricularly into rats has been investigated.

2. Intraventricular injection of angiotensin II led to a significant increase in blood pressure in the control and all sham-operated rats compared with that in unilaterally nephrectomized, one-kidney denervated rats and bilaterally nephrectomized rats. The degree of increase in blood pressure in unilaterally nephrectomized, one-kidney denervated rats was equal to that in bilaterally nephrectomized rats.

3. The increase in blood pressure in the bilaterally nephrectomized rats lasted significantly longer than that in the control and unilaterally nephrectomized, one-kidney denervated rats.

4. In the bilaterally nephrectomized rats plasma vasopressin was still higher 30 min after the intraventricular injection of angiotensin II than that of the control and unilaterally nephrectomized, one-kidney denervated rats.

5. These results suggest that the rise in blood pressure observed after intraventricular injection of angiotensin II is due partly to stimulation of the renal sympathetic nervous system and partly to increase in plasma vasopressin concentration.
Absence of Production of Natriuretic Factor following Acute Saline Expansion in Nephrotic Rats
Authors: Favre H. , Gourjon M.
Published: August 2015

1. The natriuretic activity of an extract from the kidneys was studied in control and nephrotic rats following acute saline expansion.

2. The natriuretic effect of a known natriuretic material prepared from human urine was evaluated in control and nephrotic rats.

3. After actute saline expansion, natriuretic activity was obtained only from the fractions extracted from the kidneys of the control rats.

4. Injection of natriuretic material produced a equal natriuretic response in both control and nephrotic rats.
Vascular Smooth Muscle Membrane Potential and a Ouabain-Like Humoral Factor in One-Kidney, One-Clip Hypertension in Rats
Authors: Pamnani Motilal B. , Harder David R. , Huot Stephen J. , Bryant Howard J. , Kutyna Francis A. , Haddy Francis J.
Published: August 2015

1. Transmembrane potentials (Em) of vascular muscle cells in caudal arteries in vitro from one-kidney, one-clip hypertensive and one-kidney, sham-clipped normotensive rats were measured.

2. The Em recorded in hypertensive rats was significantly lower (depolarized) than that recorded in normotensive control rats.

3. Boiled plasma supernatants from hypertensive rats depolarized the muscle cells in normotensive caudal artery but had no effect on muscle cells in arteries from hypertensive rats.

4. Boiled plasma supernatants from normotensive control rats had no effect on the Em of either animal.

5. Ouabain depolarized muscle cells of the normotensive artery only and the magnitude of depolarization induced was nearly the same as that produced by the supernatant from the hypertensive animals.

6. These data suggest that a ouabain-like humoral substance may play a role in the pathophysiology of one-kidney, one-clip hypertension through a voltage-dependent mechanism.
Dependence of Renal Vasodilator Effect of Captopril on Prevailing Plasma Renin Level in the Dog: Influence of DOCA–Salt Treatment
Authors: Wong P. C. , Zimmerman B. G.
Published: August 2015

1. The blood pressure and renal blood flow response to captopril (0·2 mg/kg, intravenously) was studied in low salt, normal, and high salt fed conscious dogs, and in a group of DOCA-salt treated dogs.

2. Mean arterial blood pressure was decreased and renal blood flow increased most in the low salt group, but significant changes were also obtained in the normal group. The high salt and DOCA-salt groups were only marginally affected by captopril.

3. When the data from all four groups of dogs were subjected to regression analysis, there was a significant relationship (r = 0·68) between the prevailing plasma renin activity and the increase in renal blood flow caused by captopril.

4. The results suggest that renal vasodilatation resulting from converting enzyme inhibition is mainly due to a decrease in the level of circulating angiotensin II, and that even in the normal conscious dog the prevailing plasma renin activity can affect blood pressure and renal blood flow.
Purine Synthesis De Novo in Lymphocytes from Patients with Gout
Authors: Gordon R. B. , Counsilman A. C. , Cross S. M. C. , Emmerson B. T.
Published: August 2015

1. Variables that affect the measurement of purine synthesis de novo in human lymphocytes were studied and a reliable method of measurement of purine synthetic activity in these cells was established.

2. Purine synthesis de novo was measured as the rate of incorporation of [14C]formate into α-N-formylglycinamide ribonucleotide when further steps in the biosynthetic pathway had been blocked by azaserine. Incubation was carried out in a synthetic medium with a high phosphate concentration (25 mmol/l).

3. Purine synthesis de novo was measured in lymphocytes obtained on several occasions both from control subjects and from patients with gout, particularly those who tended to overproduce urate as suggested by high values of urinary urate.

4. Lymphocytes obtained from each individual on different occasions showed considerable variations in purine biosynthetic activity. This variation was such that there was no difference between the mean values obtained for the gouty subjects and the control subjects.

5. No correlation was obtained between the mean purine synthetic activity de novo in lymphocytes and either the serum urate concentration or the 24 h urinary urate excretion on a purine-free diet.

6. Apart from those with recognized enzyme mutations, no subgroup of the gouty population has been demonstrated in whom isolated lymphocytes demonstrate an intrinsic abnormality of purine synthesis de novo.
Raised Intracellular Sodium Consequent to Sodium-Potassium-Dependent ATPase Inhibition Does Not Cause Myogenic Contractions of 150 μm Arteries from Rat and Guinea Pig
Authors: Mulvany M. J. , Aalkjær C. , Nilsson H. , Korsgaard N. , Petersen T.
Published: August 2015

1. We have examined effects of inhibition of Na+,K+-dependent ATPase in large and small arterial ring preparations from rats and guinea pigs.

2. Ouabain (1 mmol/l) caused myogenic contraction of rat aorta and tail artery, but had no long-lasting effect on 150 μm mesenteric and 150 μm femoral resistance vessels over a 3 h period. Much lower concentrations of ouabain (1 μmol/l) caused contraction of guinea pig aorta, but had no effect on the mesenteric and femoral resistance vessels.

3. In the mesenteric resistance vessels, ouabain (1 mmol/l, rat vessels; 1 μmol/l, guinea pig vessels) caused the intracellular sodium content to rise over 2 h from approx. 13 mmol/l to approx. 60 mmol/l, and in the rat mesenteric resistance vessels this was associated with membrane depolarization from approx. −54 mV to approx. −30 mV after 3 h.

4. The results suggest that whereas Na+,K+-ATPase inhibition and consequent raised intracellular sodium may cause contraction of large vessels, this does not seem to be the case for small vessels. It therefore seems that further investigation is required before it is accepted that raised intracellular sodium is in itself a factor of importance in the etiology of hypertension.
Evidence for a Plasma Factor Affecting Na+ Cellular Transport in Genetic Normotensive Subjects and in Borderline Hypertensive Subjects
Authors: Costa F. V. , Montebugnoli L. , Giordani M. F. , Vasconi L. , Ambrosioni E.
Published: August 2015

1. Lymphocytes from normotensive subjects with normal intralymphocytic sodium content were incubated for 1 h in plasma from subjects with essential hypertension, secondary hypertension or borderline hypertension, and from normotensive subjects with (genetic) and without (non-genetic) family history of hypertension.

2. Lymphocytes from non-genetic normotensive subjects greatly increase their intralymphocytic sodium content after incubation in plasma (diluted 1:4) of patients with essential hypertension (but not with secondary hypertension), of borderline subjects and of genetic normotensive subjects with abnormally high intralymphocytic sodium content (<26 mmol/kg).

3. When plasma is diluted 1:8, an increase in intralymphocytic sodium content is detectable only after incubation in plasma of borderline subjects and of genetic normotensive subjects with high intralymphocytic sodium content.

4. These data suggest that a plasma factor altering Na+ transport is detectable in all the subjects in whom intralymphocytic sodium content is high, independently of their blood pressure values. The concentration (or the activity) of this substance is greater in borderline and genetic normotensive subjects than in patients with sustained essential hypertension. This suggests that these subjects are in a dynamic phase of the development of hypertension.
Studies of Sodium Transport in Thymocytes of Rats with DOC/Salt Hypertension
Authors: Jones R. B. , Patrick J. , Hilton P. J.
Published: August 2015

1. Sodium transport and intracellular sodium content were studied in thymocytes of rats made hypertensive by treatment for 4 or 8 weeks with deoxycorticosterone (DOC) and salt (DOC/salt).

2. The systolic blood pressure in the DOC/salt animals was 152 ± sem 3 and 189 ± 3 mmHg after 4 and 8 weeks' treatment respectively. This was significantly higher than pressures in their respective controls (124 ± 4 and 126 ± 5 mmHg), which had been given 1% sodium chloride solution (171 mmol/l) only.

3. The total sodium efflux rate constant in the DOC/salt rats was lower than that in the control group after 8 weeks of treatment (5.56 ± sem 0.21 vs 6.12 ± 0.11 h−1; P < 0.05) but not after 4 weeks of treatment (5.93 ± 0.13 vs 6.32 ± 0.13 h−1;0.1 > P > 0.05).

4. Intracellular sodium content in the DOC/salt rats was significantly higher than that of the control animals after 8 weeks' treatment (49.6 ± 2.5 vs 42.1 ± 1.0 mmol/kg dry weight; P < 0.05).

5. No significant changes were observed in intracellular potassium content, sodium influx or ouabain-insensitive sodium efflux rate constant.
Intravital Studies on Cerebral Arteries in Hypertensive and Normotensive Rats
Authors: Johansson Barbro B. , Auer Ludwig M. , Sayama Ichiro
Published: August 2015

1. The diameters of main cortical surface branches of the middle cerebral artery were continuously monitored through a closed cranial window in spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto (WKY) rats by aid of a multichannel video-angiometer under resting conditions and under maximal vasodilatation induced by hypercapnia.

2. Initial mean arterial pressure was 172 ± sem 9 mmHg in SHR and 103 ± 5 mmHg in WKY rats; during hypercapnia the corresponding values were 183 ± 9 and 127 ± 7 mmHg.

3. The resting diameter of the arteries was 55 ± 1 μm in SHR (n = 53) and 87 ± 1 μm in WKY rats (n = 53; P < 0.001). The percentage increase in diameter during vasodilatation (Paco2 70 mmHg) was larger in SHR (54%) than in WKY rats (36%). However, the maximum lumen diameter remained significantly smaller in SHR (84 ± 2 μm compared with 117 ± 5 μm in WKY rats; P < 0.001). No significant further dilatation was seen in either group after α-adrenoceptor blockade.

4. The smaller diameter of cortical arteries during vasodilatation is consistent with the concept that hypertensive vascular hypertrophy encroaches on the lumen in vivo. The larger percentage increase in diameter of cortical arteries in hypertensive rats corroborates Folkow's hypothesis on the haemodynamic consequences of an altered media/lumen ratio in hypertension.

5. There is no evidence that an enhanced sympatho-adrenergic tone prevents maximum vasodilatation during hypercapnia in SHR.
Estimation of Forearm Arterial Compliance in Essential Hypertension: A Preliminary Report
Authors: Simon A. CH. , Levenson J. A. , Laurent S. P. , Safar M. E.
Published: August 2015

1. Simultaneous brachial artery pressure and blood flow measurements were made in 21 men, including six normal subjects and 15 patients with essential hypertension of the same age and diastolic pressure at the time of investigation.

2. Blood flow was evaluated by means of a pulsed Doppler device with a double transducer probe, enabling a precise evaluation of the calibre of the brachial artery. From analysis of the pressure-flow curves during diastole, forearm arterial compliance was estimated by using an original first-order model of the forearm arterial system.

3. Forearm arterial compliance was significantly decreased in hypertensive subjects.

4. Since patients and hypertensive subjects had similar blood pressures, the results indicate that the reduced forearm compliance was independent of blood pressure per se but may reflect in hypertensive subjects adaptive changes in the walls of peripheral large arteries.
The Relation of Arterial Pressure with Plasma and Body Electrolytes is Similar in Conn's Syndrome and Essential Hypertension
Authors: Beretta-Piccoli C. , Davies D. L. , Brown J. J. , Ferriss J. B. , Fraser R. , Lever A. F. , Morton J. J. , Robertson J. I. S.
Published: August 2015

1. Arterial pressure, exchangeable sodium (NaE), exchangeable potassium (KE) and plasma concentrations of sodium, potassium, urea, angiotension II and aldosterone were measured in 34 patients with untreated Conn's syndrome before surgical removal of their adenoma. The study was repeated in 23 patients between 3 and 12 months after the operation.

2. Plasma aldosterone, NaE and plasma sodium concentration were higher and KE and plasma potassium concentration were lower than predicted normal. Surgery corrected these abnormalities, also reducing blood pressure from an average of 183/112 to 138/86 mmHg.

3. Systolic blood pressure was positively correlated with plasma and exchangeable sodium and negatively correlated with plasma potassium concentration. The relation of NaE and arterial pressure was closer in old than in young patients. None of these correlations was significant after operation. Before operation plasma urea was insignificantly related to arterial pressure but after operation a significant and positive correlation emerged.

4. A relation between arterial pressure and NaE is to be expected in a state of mineralocorticoid excess but the different correlation in old and young patients was not expected. A similar difference exists in patients with essential hypertension.
A Role for β-Melanotropin in the Regulation of Aldosterone Secretion during Sodium Deficiency in the Rat
Authors: Yamakado Minoru , Franco-Saenz Roberto , Mulrow Patrick J.
Published: August 2015

1. The effect of sodium deficiency on adrenal sensitivity to β-melanotropin (β-melanocyte stimulating hormone; β-MSH) and the effect of β-MSH on a late step of aldosterone biosynthesis were studied using collagenase-dispersed rat adrenal cells.

2. Sodium depletion enhanced the sensitivity of the adrenal glomerulosa cells to β-MSH, resulting in a shift of the dose-response curve to the left, so that doses of β-MSH within the physiological range caused significant stimulation of aldosterone production.

3. The aldosterone level obtained by maximum doses of β-MSH was similar to that obtained after angiotensin (‘angiotensin II’; ANGII) during sodium depletion.

4. Sodium depletion did not change the corticosterone response to β-MSH by decapsular cells.

5. Similarly to ANGII, β-MSH significantly stimulated the conversion of exogenous corticosterone into aldosterone in the presence of an inhibitor of 3β-hydroxysteroid dehydrogenase, WIN 19,578.

6. These data suggest that β-MSH or peptides containing β-MSH may play a role in the regulation of aldosterone secretion during sodium depletion in the rat and that β-MSH increases aldosterone production partly by stimulating the late step in aldosterone biosynthesis, the conversion of corticosterone into aldosterone.
Generation of Inactive Renin in Vitro and in Vivo: Reversible Inactivation of the Active Plasma Enzyme in Rats
Authors: Barrett Jack D. , Eggena Peter , Sambhi Mohinder P.
Published: August 2015

1. Active and total (trypsin treatment) plasma renins were measured in normal Wistar rats and in rats in which the renin-angiotensin system was stimulated by ether anaesthesia.

2. After incubation of normal plasma in vitro in the absence of angiotensinase inhibitors, active renin declined. This decline was shown to be due to the conversion of active renin into an inactive form, which could be re-activated by trypsin.

3. In plasma from renin-stimulated rats, the rate of decline of active renin in vitro was accelerated; however, the relative amount of inactive renin generated was decreased.

4. Ligation of the kidneys of the ether-anaesthetized animal resulted in a build-up in vivo of inactive renin concomitant with the decline of active renin.

5. These data demonstrate the conversion of active into inactive renin in vitro and indicate that inactive renin can also be generated in vivo from the active form of the enzyme.

6. Multiple forms of inactive renin may exist; some may be true ‘prorenins’ (renin zymogens) produced in the kidney, and others may result from post-biosynthetic modifications of the active plasma enzyme.
Changes in Nuclear Initiation Sites after the Treatment of Isolated Nuclei with Angiotensin II
Authors: Re Richard N.
Published: August 2015

1. Angiotensin II (ANG II) increases hepatic RNA synthesis. Because the hormone apparently can be found in the cytoplasm of at least some target cells and because intracellular receptors have been demonstrated for this hormone, we investigated the direct effect of angiotensin II on isolated nuclei.

2. Nuclei were purified from rat liver and then treated for 2 h at 37°C with various concentrations of angiotensin II. Chromatin was then isolated and initiation-site number was estimated by utilizing exogenous Escherichia coli RNA polymerase.

3. Statistically significant increases in initiation-site number were noted in nuclei treated with angiotensin II suggesting that at least part of the hormone's stimulatory effect on RNA synthesis results by this mechanism. Furthermore, these observations suggest a direct nuclear effect of this peptide hormone.
Response of Blood Pressure and the Renin—Angiotensin—Aldosterone System to Chronic Ambulatory Peritoneal Dialysis in Hypertensive End-Stage Renal Failure
Authors: Glasson Ph. , Favre H. , Vallotton M. B.
Published: August 2015

1. Chronic ambulatory peritoneal dialysis allows good control of blood pressure in patients with hypertensive end-stage renal disease. The role of the renin-angiotensin-aldosterone system has therefore been studied in seven patients during the first 6 months of chronic ambulatory peritoneal dialysis treatment.

2. Steady increases in plasma renin activity and aldosterone were observed with a good correlation between these two variables. Plasma electrolytes, renin substrate and body weight did not change significantly.

3. Angiotensin II perfusion tests, performed at the end of the study, showed a relative vascular resistance to angiotensin II.

4. Stimulation of the renin-angiotensin-aldosterone system may be partially explained by this last observation or by removal of an unknown vasopressor substance responsible for the inhibition of the plasma renin activity.
Effect of Ureteral Ligation of the Contralateral Kidney on Angiotensin Dependency in One-Clip, Two-Kidney Renal Hypertensive Rats
Authors: Takata Yutaka , Doyle Austin E. , Veroni Margherita , Duffy Stuart G.
Published: August 2015

1. The aim of this study was to determine whether the urinary excretory function of the contralateral kidney is essential for angiotensin dependency in two-kidney, one-clip renal hypertensive rats. Ureteric ligation was used to abolish excretion from the contralateral kidney.

2. Plasma renin activity (PRA), renal renin content (RRC) and the response of blood pressure to captopril were examined.

3. The increase of blood pressure produced by the application of a clip to one renal artery was slightly accelerated by the ureteral ligation of the contralateral kidney.

4. Ureteral ligation of the contralateral kidney did not alter the response to a single oral administration of captopril. PRA and RRC of both kidneys were not different between the ureteral ligated group and the group without ureteric ligation. The falls in blood pressure produced by captopril correlated with PRA in the two groups.

5. These results suggest that the excretory function of the contralateral kidney is not essential for angiotensin dependency in the two-kidney, one-clip hypertensive rat model.
Effects of Moderate Salt Restriction and High Potassium Intake on Intralymphocytic Sodium Content and Pressor Response to Stress in Borderline Hypertension
Authors: Ambrosioni E. , Costa F. V. , Borghi C. , Montebugnoli L. , Giordani M. F. , Vasconi L.
Published: August 2015

1. Twenty young subjects with borderline hypertension were studied to evaluate the effects of moderate salt restriction and/or of a high potassium intake on intralymphocytic sodium content and blood pressure. Blood pressure was measured after 1 min (casual) and after 5 min (baseline) of rest and during handgrip.

2. Moderate sodium restriction (from 170 to 100 mmol of sodium/day) decreased both intralymphocytic sodium content and diastolic blood pressure at rest and during handgrip. During a high potassium diet (130 mmol of potassium/day) both intralymphocytic sodium content and baseline diastolic blood pressure rose significantly whereas casual diastolic blood pressure remained unchanged and pressor response to handgrip was reduced by 50%.

3. The increase in intralymphocytic sodium content induced by the high potassium diet was dose-dependent. A daily dose of 0.8 mmol of potassium/kg body weight produced the maximal protective effect on blood pressure during exercise with minimal effects on intralymphocytic sodium content and baseline blood pressure.

4. In borderline subjects a low sodium/high potassium diet seems to produce the most favourable effect, since intralymphocytic sodium content and baseline blood pressure remain unchanged whereas the pressor response to handgrip is reduced.
‘Vascular Kallikrein’: A Kallikrein-Like Enzyme Present in Vascular Tissue of the Rat
Authors: Nolly Héctor , Lama M. Cristina
Published: August 2015

1. The present study was undertaken to examine whether there is a kallikrein-like enzyme in vascular tissue. Isolated saline-perfused rat mesenteric arteries were used and arterial homogenate was incubated with heat-treated dog plasma and citrate/phosphate buffer (pH 8.5) in the presence of peptidase inhibitors for 60 min.

2. The kallikrein-like enzyme showed optimum activity in the range pH 7.0-9.0. The rate at which it releases kinin is similar to the release of kinin by kallikrein and trypsin. The release is unaffected by incubation of the enzyme with trypsin-inhibitors, but completely inhibited by aprotinin.

3. The kinin released by arterial homogenate resembles bradykinin in its chemical and pharmacological properties, and by using antibodies that specifically inhibit kinins, the biological action was completely abolished.

4. These results indicate that arterial tissue contains an enzyme with physicochemical characteristics quite similar to those of kallikreins of glandular origin.
Elevated Plasma Vasopressin Contributes to Fulminating Hypertension Produced by Functional Impairment of A1 Catecholamine Neurons in Rabbit Medulla
Authors: Blessing W. W. , Sved A. F. , Reis D. J.
Published: August 2015

1. Injection of the neurotoxin kainic acid into the region of the A1 noradrenergic neurons in the caudal ventrolateral medulla of rabbit increases blood pressure by 35 mmHg and plasma vasopressin five fold.

2. After cervical spinal cord transection or intravenous injection of phentolamine, kainic acid injected into the A1 area still elevates arterial pressure.

3. The increase in blood pressure produced by injection of kainic acid into the A1 area of the intact rabbit is almost completely reversed by the administration of a vasopressin antagonist.

4. A1 noradrenergic neurons tonically inhibit the release of vasopressin and the amount of vasopressin released by destruction of these cells is sufficient to elevate arterial pressure.

5. Imbalance within the central nervous system can produce hypertension by means of vasopressin release.