bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Effects of Chlorothiazide on Reabsorption by the Proximal Tubule of the Rat
Authors: Weinman E. J. , Eknoyan G.
Published: August 2015

1. The renal response to a low-sodium diet alone and a low-sodium diet plus the daily oral administration of chlorothiazide was examined in rats. Sodium restriction resulted in a decrease in sodium excretion until day 4, after which it remained constant. The administration of chlorothiazide resulted in an initial natriuresis. By day 6, however, the natriuresis had abated and thereafter sodium excretion remained the same as that of the low-sodium group.

2. After the animals were in balance on their respective regimens, clearance and micropuncture studies were performed. The glomerular filtration rate was lower in the chlorothiazide-treated rats than in control rats and/or in the low-sodium group. End proximal tubule TF/Pinulin ratios were higher in the diuretic-treated animals than in control rats. TF/Pinulin ratios in low-sodium animals were lower than in the diuretic-treated animals but higher than in control rats.

3. These studies demonstrate that the escape from the chronic effects of chlorothiazide is due to a decrease in the glomerular filtration rate and to an increase in fractional reabsorption in the proximal tubule, resulting in a reduction in delivery of filtrate to the cortical diluting segment where chlorothiazide exerts its major inhibitory effect.
Effect of Progesterone on Renal Sodium Handling in Man: Relation to Aldosterone Excretion and Plasma Renin Activity
Authors: Oparil Suzanne , Ehrlich E. N. , Lindheimer M. D.
Published: August 2015

1. The effect of progesterone on renal haemodynamics and intrarenal sodium handling was evaluated in thirteen normal men on a constant diet. Clearances were measured during maximal water diuresis and again 4–7 days later, this time 3 h after progesterone was given intramuscularly. Seven additional studies were performed 3 days after progesterone administration. Another four tests were performed on volunteers who had manifested renal ‘escape’ from the sodium-retaining effect of deoxycorticosterone acetate.

2. In acute progesterone studies glomerular filtration rate was unchanged, whereas effective renal plasma flow increased, so that filtration fraction decreased significantly. A similar increase in urinary sodium occurred whether subjects received a low or high sodium diet. Indices which related to the distal delivery of filtrate (fractional urine flow and the sum of fractional free water and sodium clearances) increased significantly in both groups. The progesterone-induced increase in sodium excretion was not related to changes in plasma renin activity, renin substrate or urinary aldosterone. After 3 days of progesterone, the increase of sodium excretion was less than in the acute studies and urinary aldosterone increased two- to four-fold. Progesterone failed to produce an acute increase in urinary sodium in subjects hyperexpanded by administration of exogenous mineralocorticoids.

3. Results suggest that the acute natriuretic action of progesterone is in part independent of aldosterone inhibition and that progesterone may inhibit sodium reabsorption at proximal as well as distal sites in the nephron.
Soluble High-Molecular-Weight E Fragments in the Plasmin-Induced Degradation Products of Cross-Linked Human Fibrin
Authors: Gaffney P. J. , Lane D. A. , Brasher M.
Published: August 2015

1. The factor XIII-mediated cross-linked α chains in fibrin have no effect on the nature of the fragments released during the solubilization of fibrin by plasmin.

2. Besides the known D dimer and E fragments solubilized during the lysis of cross-linked fibrin, other fragments have been observed on sodium dodecyl sulphate-polyacrylamide gel electrophoresis which have a molecular weight of about 135 000. After prolonged plasmin digestion, these fragments (U fragments) were no longer evident on the gels and the high-molecular-weight E antigen was absent. It is assumed that the E antigen was associated with the U fragments. These fragments also cross-reacted with an anti-D serum.

3. The U fragments have been tentatively presumed to be a factor XIII-mediated cross-linked D–E complex since they degrade only after prolonged degradation with plasmin. Whereas it is known that the fibrin D dimer fragment contains the cross-linked γ chain residues of the originating fibrin, the presumed covalent cross-linking of the D–E fragments has not been proved.

4. The presence of these high-molecular-weight fragments, containing the E antigen, in cross-linked human fibrin digests should be taken into account in the development of D dimer assays to monitor fibrin lysis in vivo.
Exaggerated Phosphaturic Response to Volume Expansion in Patients with Essential Hypertension
Authors: Chaimovitz C. , Spierer A. , Leibowitz H. , Tuma S. , Better O. S.
Published: August 2015

1. Tubular handling of sodium in hypertensive patients has been evaluated with urinary phosphate excretion used as a marker for proximal tubular reabsorptive capacity.

2. Nine hypertensive patients and nine normal control subjects were studied during sustained water diuresis and the intravenous infusion of isotonic sodium chloride solution to produce volume expansion.

3. In the hypertensive patients there was exaggerated phosphaturia, natriuresis and enhanced distal delivery of sodium. Sodium reabsorption in the diluting segment was normal.

4. The enhanced distal delivery and augmented phosphaturia suggest that a decreased reabsorption of sodium in the proximal tubule is the most likely explanation for the exaggerated natriuretic response to volume expansion in hypertensive patients.
Defective Membrane Systems in Dystrophic Skeletal Muscle of the UM-X7.1 Strain of Genetically Myopathic Hamster
Authors: Dhalla N. S. , Singh A. , Lee S. L. , Anand M. B. , Bernatsky A. M. , Jasmin G.
Published: August 2015

1. The function of mitochondria, sarcotubular membranes (heavy microsomes), sarcolemma and myofibrils from the hind-leg skeletal muscle of about 60- and 150-day-old normal and myopathic (UM-X7.1) hamsters was examined.

2. The mitochondrial calcium uptake as well as mitochondrial phosphorylation and respiratory rates were lower in 60-day-old myopathic skeletal muscle, unlike 150-day-old myopathic animals, when pyruvate-malate and glutamate-malate were used as substrates. However, mitochondria from 150-day-old myopathic animals showed depressed glutamate-dependent respiratory and phosphorylation rates and succinate-supported initial rate of calcium uptake.

3. The microsomal calcium-uptake, but not calcium-binding, and Ca2+-stimulated adenosine triphosphatase (ATPase) activity of the 150-day-old myopathic skeletal muscle were lower than the control values. Although microsomal calcium-binding, calcium-uptake and ATPase activities of the 60-day-old myopathic muscle were not depressed significantly, the initial rate of calcium uptake was less than the control.

4. The sarcolemmal Ca2+-ATPase, but not Mg2+-ATPase or Na+ +K+-ATPase, activity was higher in 60-day-old myopathic muscle whereas the activities of all these enzymes from 150-day-old myopathic animals were higher than the control. On the other hand, the Na+ +K+-ATPase activities from 60- and 150-day-old myopathic animals were inhibited by ouabain to a lesser extent in comparison with the respective control values.

5. The myofibrillar Ca2+-ATPase and Mg2+-ATPase activities as well as inhibition of Mg2+-ATPase due to Na+ and K+ in myopathic muscle were no different from the control values.

6. The results reported here give further support to the view that different membrane systems of the dystrophic muscle are defective.
I-cell disease (mucolipidosis II): Resolution of N-acetyl-β-d-glucosaminidase and α-l-fucosidase components by DEAE-cellulose chromatography
Authors: Ellis R. B. , Willcox P. , Patrick A. D.
Published: August 2015

1. In a patient with I-cell disease the activities of several acid hydrolases were elevated in plasma and reduced in cultured fibroblasts when compared with normal values. Normal activities for the enzymes were found in leucocytes. These findings agree with reports on other cases.

2. N-Acetyl-β-d-glucosaminidase was resolved into its component forms by chromatography on microcolumns of DEAE-cellulose coupled with continuous automated assay of activity in the column effluent. Cultured skin fibroblasts from three patients showed a profound deficiency of glucosaminidase component A and a relative increase in the activity of a form eluted earlier than A.

3. In the one patient studied, the elution profile of plasma glucosaminidase was similar to that of normal plasma, but treatment with neuraminidase revealed a minor component which did not appear in control specimens.

4. Chromatographic resolution of glucosaminidase secreted by normal fibroblasts into the culture medium showed that component A comprised two forms, a serum-type and a tissue-type, whereas only a serum-type was found in I-cell medium.

5. Different forms of α-l-fucosidase were shown to occur in normal plasma and fibroblasts. This is the second lysosomal hydrolase for which differences between intracellular and extracellular forms have been described and might reflect a general phenomenon.

6. The major acidic component of fucosidase from normal fibroblasts was not detected in I-cell fibroblasts. Elution profiles of fucosidase activity in normal and I-cell plasma were indistinguishable, both before and after treatment with neuraminidase.

7. On the basis of the above findings, we suggest that for several acid hydrolases there is a common biosynthetic reaction, which produces forms of these enzymes destined for incorporation into primary lysosomes rather than secretion by the cell. In cultured fibroblasts from patients with I-cell disease, the enzyme catalysing the reaction leading to the production of intracellular forms is deficient or defective, whereas the synthesis of precursor and secreted forms is unaffected.
The Relationship between Dietary Fat Composition and Plasma Cholesterol Esterification in Man
Authors: Miller J. P. , Chait A. , Lewis B.
Published: August 2015

1. Cholesterol esterification has been studied in the plasma of subjects on diets rich in saturated or polyunsaturated fat.

2. The diet rich in polyunsaturated fat was associated with lower rates of plasma cholesterol esterification in vitro. The data suggest that there was a reduction of plasma lecithin—cholesterol acyltransferase activity as well as decreased ability of the lipoprotein substrates of the enzyme to support esterification.

3. On this diet, there was no change in the proportion of the plasma cholesterol esterified but the plasma cholesterol and triglyceride concentrations were reduced.
Plasma Prostaglandin E during Neurogenic Hypertension in Tetraplegic Man
Authors: Mathias C. J. , Hillier K. , Frankel H. L. , Spalding J. M. K.
Published: August 2015

1. Arterial blood pressure and heart rate were measured before, during and after cutaneous and visceral stimulation in subjects tetraplegic due to severe cervical spinal cord damage. Stimulation resulted in marked hypertension as a result of reflex sympathetic overactivity.

2. Mixed venous blood from a catheter situated in the right atrium was obtained before and after stimulation and plasma prostaglandin E and prostaglandin F were measured. A consistent and significant rise in plasma prostaglandin E, but not plasma prostaglandin F, accompanied the hypertension.

3. It is suggested that prostaglandin E is released during this sympathetic nervous activity and may be related to neurogenic hypertension.
Ventilatory Response to Carbon Dioxide in Tetanus
Authors: Elegbeleye O. O. , Femi-Pearse D.
Published: August 2015

1. Ventilatory response to carbon dioxide was measured by the rebreathing technique in seven patients with mild tetanus during the disease state and after clinical recovery.

2. The ventilatory response to carbon dioxide was found to be decreased in the tetanus patients during the disease state with normal response after full clinical recovery. It is postulated that the restrictive ventilatory defect was responsible for the decreased ventilatory response to carbon dioxide.
Urinary Excretion of Hydroxylysyl Glycosides during Acute Inflammation in the Rat
Authors: Askenasi R. , Le Lous M. , Bazin S. , Rao V. H.
Published: August 2015

1. Subcutaneous inflammatory granuloma were induced in young rats and the urinary excretion of hydroxyproline and hydroxylysyl glycosides was observed during the period of acute inflammation.

2. All collagen metabolites were increased in the urine and excretion of glucosyl-galactosyl-hydroxylysine was much greater than excretion of galactosyl-hydroxylysine in the first days.

3. It is argued that urinary glucosyl-galactosyl-hydroxylysine is probably derived from hydroxylysyl residues of soluble collagen.

4. This study affords new arguments in favour of the dermal origin of urinary glucosyl-galactosyl-hydroxylysine, at least in skin inflammation.
The Pressure—Volume Relationship in Normotensive and Permanent Essential Hypertensive Patients
Authors: Safar M. E. , Chau N. PH. , Weiss Y. A. , London G. M. , Simon A. CH. , Milliez P. P.
Published: August 2015

1. Blood pressure, blood volume and renal blood flow were determined in 101 men; forty-three were normal subjects and fifty-eight were untreated permanent essential hypertensive patients with normal renal function and equilibrated sodium balance.

2. A significant negative pressure—volume relationship was observed overall. The relationship could be expressed as a hyperbola whose slope expressed the reduction in blood volume per unit rise in pressure: the higher the blood pressure, the lower the slope. Thus essential hypertensive subjects have a smaller decrement in blood volume per unit rise in pressure than normal subjects.

3. The relation between change in blood volume and change in pressure was confirmed in each individual by defining for each a ratio ΔV/ΔP, statistically identical with the hyperbolic slope dV/dP. The ΔV/ΔP ratio was found to be well correlated with the renal blood flow and the creatinine clearance. No correlation existed between the total blood volume and these two renal parameters.

4. It is concluded that the present study demonstrates a blood volume regulation disturbance in essential hypertension and provides evidence from human studies that a renal defect accompanies high blood pressure.
Growth Hormone Secretion in Acid-Base Alterations at Rest and during Exercise
Authors: Sutton J. R. , Jones N. L. , Toews C. J.
Published: August 2015

1. Seven healthy males were studied during cycle ergometer exercise at 33%, 66% and 90% of V̇o2 max. on three occasions when NH4Cl, NaHCO3 or CaCO3 (as a control substance) were administered in gelatin capsules double blind and in randomized order. Plasma growth hormone (HGH), lactic acid and hydrogen ion concentration ([H+])weremeasured at frequent intervals.

2. Ammonium chloride produced highest blood [H+] and NaHCO3 the lowest. These differences were maintained during exercise and in recovery. Plasma lactic acid concentrations were similar at rest. At 66%, 90% V̇o2 max. and recovery lactic acid was highest with NaHCO3 and lowest with NH4Cl.

3. Exercise stimulated HGH secretion in all studies and the elevation was proportional to the intensity of the exercise. NH4Cl caused a variable elevation of HGH at rest and 33% V̇o2 max. At 66% V̇o2 max., plasma HGH was significantly elevated to similar concentrations in all studies and, at 90% V̇o2 max., HGH was highest with NaHCO3.

4. An infusion of sodium l(+)-lactate producing plasma lactate concentrations of 3–5 mmol/l did not influence HGH secretion.

5. Exercise is a physiological stimulus to HGH secretion and the mechanism is independent of blood [H+] and lactate concentrations.
The Influence of Sodium Intake on the Pressor Response to Angiotensin II in the Unanaesthetized Rat
Authors: Slack Barbara L. , Ledingham J. M.
Published: August 2015

1. Dose—response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2·5% (w/w) or 0·007% (w/w) sodium; the different diets were administered in various sequences.

2. In comparison with those from rats receiving a low sodium diet, the dose—response curves were displaced to the left on the high sodium diet, indicating a greater response to angiotensin, and this displacement persisted for a period of approximately 7 days after the diet was changed from high to low sodium. The dose—response curve subsequently shifted to the right when the low sodium diet was maintained for longer.

3. There was a negative correlation between the slope of the dose—response curve and the basal blood pressure in all groups; the correlation was significant in three out of the five different treatment groups.

4. Basal blood pressures were significantly raised in rats on the high sodium diet for 7 days.

5. A number of possible mechanisms have been considered to explain both the parallel shift of the dose—response curve and alteration in its slope. It is concluded that the observed findings are compatible with an action of sodium-loading on the sensitivity of the smooth muscle cell to angiotensin, on the resting of the renin—angiotensin system, on the rate of in-activation of angiotensin and on a change in initial length of the muscle fibre.
The Spectrophotometric Determination of Human Serum Carboxypolypeptidase with Angiotensin Converting Enzyme-Like Activity
Authors: Summary J. J.
Published: August 2015

1. A colorimetric method was developed for the direct chemical assay of human carboxypeptidase A (carboxypolypeptidase; EC 3.4.12.2) with angiotensin converting enzyme-like activity in serum or plasma, with the substrate analogue glycyl-l-histidylglycine and the angiotensin converting enzyme substrate angiotensin I (A-I). This method was based on the spectrophototometric determination of histidylglycine and histidyl-leucine, products of the hydrolysis of glycyl-l-histidylglycine and A-I respectively. o-Phthalaldehyde reacted with the imidazole moiety of N-terminal histidyl peptides to produce a yellow chromophore.

2. A large number of inhibitors were tested for their effects on carboxypolypeptidase activity. The hydrolysis of Gly-His-Gly and A-I was inhibited by histidyl-leucine and angiotensin II, both products of the hydrolysis of A-I. Bothrops jararaca venom extract, EDTA, p-chloromercuribenzoate, 8-hydroxyquinoline and 2,3-dimercaptopropanol, previously reported as converting enzyme inhibitors, also inhibited carboxypolypeptidase activity.

3. Angiotensin converting enzyme activity in the serum of sixty-six adults ranged from 10 to 37 nmol of glycyl-l-histidylglycine hydrolysed in 10 min by 10 μl of serum at 37°C and pH 7·25.
Rat Hepatic Sodium plus Potassium Ion-Dependent Adenosine Triphosphatase after Treatment with Digoxin and Thyroxine
Authors: Lindsay R. , Parker J. L. W.
Published: August 2015

1. The effect of treating rats with digoxin and thyroxine for 45 days has been studied.

2. Animals fed with digoxin gained significantly more weight than the control animals.

3. Treatment with digoxin, thyroxine or both produced a similar significant increase in the amount of Na+ + K+-dependent adenosine triphosphatase in liver without an additive effect.

4. It is suggested that digoxin resistance in thyrotoxicosis may be related to this similarity in action.
Bone-Resorbing Activity in the Sera of Patients with Rheumatoid Arthritis
Authors: Kennedy A. C. , Lindsay R. , Buchanan W. W. , Allam B. F.
Published: August 2015

1. Foetal rat hemi-calvaria were incubated in organ culture with sera from patients with active rheumatoid arthritis.

2. Increased 45Ca resorption was produced by sera from patients who were hypercalcaemic.

3. This bone-resorbing effect could be inhibited by calcitonin.
The Renal Vascular Lesions of Severe and Malignant Hypertension: A Light-Immunofluorescent Microscopy, Transmission and Scanning Electron-Microscopy Study
Authors: Jones D. B.
Published: August 2015

1. Arterial and glomerular lesions were studied in seventy-eight specimens from patients with severe or malignant primary or secondary hypertension by transmission and scanning electron microscopy and light-microscopy and immunofluorescent microscopy.

2. The lesions were classified as compensatory, decompensated and reparative. The arterial lesions of primary and secondary hypertension were qualitatively similar. Each of the microscopy techniques contributed to a better understanding of the changes.
Effects of Immersion in Water and Changes in Intrathoracic Blood Volume on Lung Function in Man
Authors: Burki N. K.
Published: August 2015

1. In healthy, normal subjects simultaneous peripheral venous occlusion of all four limbs caused a small but significant increase in vital capacity (VC) and single-breath carbon monoxide transfer factor (DLCO) without significantly changing total lung capacity (TLC), residual volume (RV), pulmonary gas flow or pulmonary compliance.

2. Immersion in water to the neck resulted in a small but significant fall in VC, FEV1.0/FVC and TLC, and a rise in DLCO, but flow/volume curves and ‘closing volume’ were unchanged. Peripheral venous occlusion during immersion only significantly increased VC and DLCO; pulmonary compliance and flow/volume curves did not alter significantly.

3. It is concluded that peripheral venous occlusion produces these effects by altering intrathoracic blood volume. Water immersion reduces TLC, mainly from the hydrostatic pressure, and VC is reduced from both the hydrostatic pressure and the increase in intrathoracic blood volume consequent on immersion. The increase in DLCO is due, almost entirely, to the increase in intrathoracic blood volume.
The Effect of pH on Folic Acid Absorption in Man
Authors: MacKenzie J. F. , Russell R. I.
Published: August 2015

1. Pteroylmonoglutamic acid (PteGlu) absorption has been measured by using the technique of small-intestinal perfusion with tritiated PteGlu in normal subjects and in patients with coeliac disease.

2. At similar intrajejunal pH, patients with untreated coeliac disease have significantly less PteGlu than normal subjects and patients with treated coeliac disease.

3. The ‘resting’ pH in the jejunum did not differ markedly between normal subjects and patients with coeliac disease.

4. Increasing pH decreased PteGlu absorption in patients with coeliac disease and in normal subjects.

5. These findings suggest that PteGlu malabsorption in coeliac disease is not due to abnormally high pH in the jejunum.
Elimination of Cholesterol in Hyperlipoproteinaemia
Authors: Angelin B. , Einarsson K. , Hellström K. , Kallner M.
Published: August 2015

1. Cholesterol intake (about 0·25 mmol/day) and the faecal excretion of cholesterol, coprostanol and coprostanone were determined in normolipidaemic control subjects and hyperlipidaemic patients, whose bile acid kinetics had been previously studied.

2. The combined excretion of the neutral steroids (excluding plant sterol and plant sterol metabolites) averaged 1·07 ± 0·13 (± sem) mmol/day in the control subjects (n = 14). The corresponding values in patients with hyperlipoproteinaemia type IIa (n = 19), II (n = 12) and IV (n = 23) were 0·86 ± 0·10, 0·93 ± 0·11 and 1·48 ± 0·17 mmol/day respectively.

3. The mean values for the net steroid ‘balance’, defined as the combined amount of bile acid synthesized (determined by an isotope-dilution technique) and the faecal excretion of neutral steroids minus cholesterol intake, were 1·83 ± 0·22 mmol/day in the control subjects and 1·60 ± 0·15, 1·81 ± 0·19 and 3·53 ± 0·23 mmol/day in patients with type IIa, IIb and IV lipoprotein patterns respectively.

4. No significant correlations between net steroid ‘balance’ and sex, age, serum lipid concentrations, body weight or body surface area were found in any of the groups of subjects.

5. It is concluded that patients with type II hyperlipoproteinaemia eliminate cholesterol as bile acids and neutral faecal steroids normally. The type IV lipoprotein pattern is associated with increased bile acid synthesis and/or elevated faecal excretion of neutral steroids, so that the net steroid ‘balance’ is usually above the normal limit.
Changes in Cardiac and Hepatic Glucocorticoid Receptors after Adrenalectomy
Authors: Gregory M. C. , Duval D. , Meyer P.
Published: August 2015

1. The total number of specific dexamethasone-binding sites in rat heart and liver cytosol was measured at intervals after adrenalectomy.

2. Between 12 and 48 h after adrenalectomy there was a significant increase in the number of binding sites in both heart and liver cytosol. Affinity was unchanged.

3. Of the [3H]corticosterone bound to liver cytosol proteins after an intravenous injection 98% disappeared within 2 h in vivo. Dissociation of endogenous corticosterone-receptor complexes in liver cytosol will thus be substantially complete some hours before the number of receptors increases.

4. It was concluded that there is a true increase in the number of glucocorticoid receptors occurring principally between 12 and 48 h after suppression of endogenous steroids.
Evidence for Peripheral Vascular Involvement in Mild Elevation of Blood Pressure in Man
Authors: Sivertsson R. , Sannerstedt R. , Lundgren Y.
Published: August 2015

1. Cardiac output at rest, intra-arterial blood pressure and hand blood flow at maximal vasodilatation were studied in two groups of 18–25-year-old men: forty-four with mild blood pressure elevation were referred from a military enlistment centre, and twenty-nine normotensive volunteers were mainly recruited from the same enlistment centre.

2. The study group was characterized by a significantly higher cardiac index at rest, and a significantly higher blood flow resistance in the hand at maximal vasodilatation than the control group, indicating the presence of structural modifications in the resistance vessels of patients with mild blood pressure elevation.

3. The tendency to increased vascular resistance in the blood vessels of the hand at maximal vasodilatation was more pronounced in patients with a normal cardiac index than in those with a high index. This suggests inclusion in the study group of tense, anxious individuals with an elevated cardiac index but otherwise normal circulation, but does not exclude the possibility that these patients may develop structural changes later on.
The Intrarenal Release of Renin in the Rat
Authors: Morgan T. O. , Davis J. , Gillies A.
Published: August 2015

1. A technique was developed to measure renin concentration in nanolitre volumes of blood.

2. The renin concentration in renal venous blood was higher than in renal arterial blood.

3. The renin concentration in blood from the efferent arteriole was less than in blood from the renal artery and renal vein.

4. Renin enters the circulation distal to the efferent arteriole.

5. The release of renin into the interstitium would allow local formation of angiotensin and the system could act as an intrarenal control mechanism.
Role of the Renal Nerves in Renin Release during Suprarenal Aortic Stenosis in Cats
Authors: Stella A. , Calaresu F. , Zanchetti A.
Published: August 2015

1. Renin release from an intact, innervated kidney and from the contralateral denervated kidney was measured before and during a period of suprarenal aortic stenosis.

2. Aortic stenosis of 10 min duration reduced renal perfusion pressure to 50 mmHg and increased renin release from both kidneys, but the response from the innervated kidney was greater.

3. A study of the time-course of the response during 30 min of aortic stenosis showed that the difference in rate of renin release between the innervated and the denervated kidney is greatest during the first few minutes of aortic stenosis.
Stimulation of Renin Secretion by Frusemide and Diazoxide in the Isolated Rat Kidney
Authors: Vandongen R. , Greenwood Dianne M.
Published: August 2015

1. The effect of diazoxide (17·3 μmol min—1 g—1) and frusemide (0·12 μmol min—1 g—1) on renin secretion was examined in the isolated perfused rat kidney. These substances are potential renal vasodilators with opposite effects on urine sodium excretion.

2. Both agents significantly increased renin secretion rate above control values. In the case of frusemide this was not altered by ureteric occlusion and presumed absence of urine flow.

3. Mean renal perfusion pressure decreased to the same extent with diazoxide and frusemide infusion as in the control experiments and no additional vasodilatory effect was observed on the basis of changes in flow rate of perfusate.

4. These observations identify an intrarenal site of action for diazoxide and frusemide on renin secretion. The apparent independence of this stimulatory action on renal vasodilatation and urine flow suggests a direct effect on the renin-producing cell.
Exchangeable Sodium in Experimental Hypertension in Rats
Authors: Doyle A. E. , Duffy S. , MacDonald G. J.
Published: August 2015

1. Total exchangeable sodium was measured in rats by a radio-sodium equilibration method, before and after the production of hypertension by clipping the left renal artery, with or without contralateral nephrectomy.

2. Clipping of one renal artery with removal of the other kidney produced severe hypertension with no significant changes in exchangeable sodium or plasma renin levels.

3. Clipping of one renal artery without contralateral nephrectomy produced severe hypertension in some animals, but little change in blood pressure in others. The animals which developed severe hypertension had a marked increase in exchangeable sodium with a concomitant rise in plasma renin; the animals with smaller rises in blood pressure did not have these changes.

4. The fact that both plasma renin levels and exchangeable sodium levels increase according to this method, suggests that hypertension in the two-kidney model is renin-dependent.
Studies on the Effect of Angiotensin II and of Des1-angiotensin II on Blood Pressure, Plasma Renin Activity and Plasma Aldosterone in the Dog
Authors: Beckerhoff R. , Uhlschmid G. , Vetter W. , Siegenthaler W.
Published: August 2015

1. The effects of infusions of equimolar doses of angiotensin II (AII) and of Des1-angiotensin II (heptapeptide) on plasma renin activity, blood pressure and plasma aldosterone were compared in normal anaesthetized dexamethasone-suppressed dogs.

2. Plasma renin activity was equally suppressed by both compounds. The increase in blood pressure induced by the heptapeptide averaged 43–62% of the increase during AII infusions. No significant differences in aldosterone increase were observed between AII and the heptapeptide. Plasma aldosterone, however, dropped significantly faster in heptapeptide-treated dogs after the end of the infusions.

3. Sar1-Ala8-angiotensin II (saralasin, 400 pmol min—1 kg—1) suppressed plasma aldosterone that was stimulated by heptapeptide (20 pmol min—1 kg—1) completely. The same angiotensin antagonist had only a moderate effect on plasma aldosterone stimulated by AII. After stopping the antagonist infusion, plasma aldosterone rose significantly higher in dogs infused with AII than in those receiving the heptapeptide.

4. The results demonstrate differences between the effects of AII and the heptapeptide both on blood pressure and on plasma aldosterone. They do not support the hypothesis that the heptapeptide may be the main mediator of aldosterone secretion.
Dissociation of Blood Angiotensin II and Plasma Renin Activity during Chronic Treatment in Essential Hypertension
Authors: Sambhi M. P. , Barrett J. D. , Eggena P. , Thananopavarn C.
Published: August 2015

1. Plasma renin activity and circulating amounts of blood angiotensin II were measured in twenty-six patients with uncomplicated essential hypertension.

2. Measurements were made during a control period and at 1, 4, 9 and 14 weeks of diuretic treatment with metolazone or hydrochlorothiazide.

3. Linear regression analysis indicated a progressive change in the relation of plasma renin activity and blood angiotensin II.

4. During chronic diuretic therapy (beyond 14 weeks) blood angiotensin II had stabilized to low and relatively fixed values across a wide range of plasma renin activities.
The Role of Vascular Capacitance in the Genesis of Essential Hypertension
Authors: Ulrych M.
Published: August 2015

1. Analysis of relationships between blood volume, vascular capacitance, cardiopulmonary and peripheral blood volumes, labelled albumin disappearance rate, plasma renin activity, blood pressure and age was performed in essential hypertensive males.

2. The results indicate that capacitance bed constriction probably occurs with age in essential hypertension leading to an increase in the product blood volume × vascular capacitance tone even in the presence of low blood volume.

3. A metabolic defect in the venous vascular bed along with an abnormality of regulation of renal sodium excretion is postulated.
The Effect of Intravenous Angiotensin II on the Peripheral Circulation with Particular Reference to its Bearing on General Haemodynamics
Authors: Cachovan M. , Brod J. , Bahlmann J. , Sippel R. , Celsen B. , Hundeshagen H.
Published: August 2015

1. Central and peripheral haemodynamic effects of intravenous infusion of angiotensin II have been investigated in ten normotensive subjects. Angiotensin II was given at the rate of 0·12–5·0 μg/min.

2. The pressor response to angiotensin II was accompanied by a significant increase in the total peripheral resistance, central venous pressure and by a marked reduction of the intravascular forearm volume and venous distensibility. Forearm circulation time was shortened.

3. Cardiac index, heart rate, forearm vascular resistance and the forearm blood flow did not change significantly in the whole group but in the individual subjects some of the variables changed markedly in either direction.

4. Direct action of angiotensin II on the vessels and its central and peripheral sympathomimetic action as well as the role of the baroreflex as responsible causes for haemodynamic changes after angiotensin II are discussed.
Vascular Actions of Frusemide and Bumetanide on the Rat Superior Mesenteric Vascular Bed: Interactions with Prostaglandins
Authors: Horrobin D. F. , Manku M. S. , Mtabaji J. P.
Published: August 2015

1. The addition of frusemide or bumetanide to perfusion fluid inhibited the response of the isolated mesenteric vascular bed to noradrenaline.

2. Addition of prostaglandin E2 to the perfusion fluid completely restored the response to noradrenaline.

3. Inhibition of prostaglandin secretion by indomethacin with restoration of responses to noradrenaline by the addition of exogenous prostaglandin E2 prevented the inhibitory effect of frusemide or bumetanide on responses to noradrenaline.

4. The inhibitory effects of diuretics on responsiveness to noradrenaline is mediated by blockade of endogenous prostaglandin synthesis.
Isolation of Renal Membranes that Contain Kallikrein, Angiotensin I-Converting Enzyme (Kininase II) and Angiotensinase in the Rat
Authors: Ward P. E. , Erdös E. G. , Gedney C. D. , Dowben R. M. , Reynolds R. C.
Published: August 2015

1. Fractions highly enriched in plasma membrane, endoplasmic reticulum or brush border were prepared from rat kidney cortex. Kallikrein was concentrated in the plasma membrane fraction, but not in the brush border fraction. Angiotensin I-converting enzyme (kininase II) and angiotensinase were localized in the brush border membrane.

2. It is suggested that kallikrein in the urine may originate from plasma membrane distal to the brush border of proximal tubules and the conversion of angiotensin I and the inactivation of bradykinin and angiotensin II may occur on the lumen membrane of the proximal tubular cells.
Role of Steroids in Hypertension: Evaluation of Plasma Mineralocorticoid Activity with Aldosterone Receptors
Authors: Baxter J. D. , Schambelan M. , Matulich D. T. , Spindler B. J. , Bartter F. C.
Published: August 2015

1. A competitive ‘mineralocorticoid’ receptor-binding technique has been used to study plasma ‘mineralocorticoid’ activity in normal and hypertensive states. The binding reaction mixture contains the competitor steroids in undiluted plasma, [3H]aldosterone and rat kidney slices. Thus plasma binding and receptor occupancy can be simultaneously considered.

2. Competitor activities relative to that of aldoterone (100%) were: deoxycorticosterone (DOC), 16%; Cortisol, 0·4%; 18-hydroxydeoxycorticosterone (18-OH-DOC), 0·1%; 16β-OH-dehydroepiandrosterone and 16-oxo-androstenediol, inactive. (Binding characteristics for aldosterone and the other steroids tested with the rat receptor were found to be similar to those with receptors in slices from human kidney, obtained at operation.) These steroids and the spironolactone SC14266 were less active in plasma than in buffer, suggesting that they bind significantly to plasma and that this reduces their capacity to occupy the receptors.

3. These competition data also suggest that at normal and even mildly elevated concentrations, Cortisol does, but DOC and 18-OH-DOC do not, contribute significantly to the plasma mineralocorticoid activity. Competitor activity in plasma samples taken at 12.00 hours from normal subjects (upright) was greater than that in those taken at 08.00 hours (supine). This physiological change, corresponding to an increase in aldosterone, was detected even though there was an associated decrease in plasma Cortisol. Competitor activity in plasma from patients with primary aldosteronism was markedly elevated as compared with that of normal subjects. However, an increase in plasma steroids which bind to the mineralocorticoid receptor was not detected in plasma from patients with ‘low-renin essential hypertension’.
SC 23992: Radioreceptor Assays for Therapeutic and Side Effects
Authors: Funder J. W. , Mercer J. , Hood J.
Published: August 2015

1. A new spirolactone (SC 23992) has been assayed in vitro to determine its affinity for mineralo-corticoid and androgen receptors.

2. Although two to eight times as potent an anti-aldosterone agent as Aldactone in vivo, SC 23992 has only ∼10% the potency in vitro.

3. This discrepancy between potency in vivo and in vitro appears to be explained on radioreceptor assay of the principal metabolites of Aldactone and SC 23992.

4. SC 23992 may represent an antimineralocorticoid with less antiandrogen side effects.
Effect of Intraventricular Perfusion of Angiotensin II in Conscious Normal Rats and in Rats with Hereditary Hypothalamic Diabetes Insipidus
Authors: Hutchinson J. S. , Schelling P. , Möhring J. , Ganten D.
Published: August 2015

1. Artificial cerebrospinal fluid was perfused through the cerebral ventricles of conscious rats. A basal secretion rate of 16 ± 3 × 10—15 mol of immunoreactive angiotensin 11/min was calculated for intact rats.

2. Most of the immunoreactive angiotensin II consisted probably of the heptapeptide or pentapeptide angiotensin II fragments.

3. The pressor responses to intraventricular perfusions of angiotensin II were normal in Long—Evans rats, virtually absent in rats homozygous for hereditary hypothalamic diabetes insipidus, irrespective of whether they were injected with vasopressin tannate or not, and intermediate in rats heterozygous for hypothalamic diabetes insipidus.

4. The results suggest that the pressor response to intraventricular angiotensin II is related to the release of vasopressin.
Reduction of the Hypotensive Effect of Clonidine and α-Methyldopa by Various Psychotropic Drugs
Authors: Van Zwieten P. A.
Published: August 2015

1. In chloralose-anaesthetized cats the centrally induced hypotensive effect of clonidine, and in some cases α-methyldopa, was diminished by pretreatment with a variety of tricyclic antidepressants and neuroleptic agents.

2. The interaction is assumed to occur at the central α-adrenoreceptors. Clonidine or α-methylnoradrenaline (from α-methyldopa) are the agonists, and the aforementioned psychotropic drugs are the antagonists.

3. Psychotropic drugs which are not α-receptor blockers, like butyrophenone neuroleptics (pimozide and haloperidol) or benzodiazepine tranquillizers, do not significantly diminish the centrally induced hypotensive effect of clonidine.
Noradrenaline Sensitivity of an Isolated Perfused Artery: Effects of Normal and Hypertensive Plasma
Authors: Rosendorff C. , Bloom D. S. , Stein M. G.
Published: August 2015

1. The noradrenaline sensitivity of the isolated perfused rabbit artery was studied, during perfusion with Krebs solution, normal plasma, hypertensive plasma and a low-density lipoprotein (LDL) extract of normal plasma.

2. There was no difference in noradrenaline sensitivity between arteries perfused with Krebs and normal plasma.

3. Both hypertensive plasma and LDL potentiated the noradrenaline-induced vasoconstriction.

4. This potentiation was associated with increases in both the intrinsic activity of the drug-receptor complex and the drug—receptor affinity.

5. There is a circulating factor in the plasma of hypertensive patients which sensitizes arteries to noradrenaline, and this factor may be LDL.
Clinical and Haemodynamic Study of a new Vasodilator Drug L6150 (3-[bis-(2-Hydroxyethyl)Amino]-6-Hydrazinopyridazine) in Man
Authors: Brod J. , Bahlmann J. , Cachovan M. , Dahlgrün H. , Pretschner P. , Futterová M.
Published: August 2015

1. L6150 is a highly effective vasodilator which produces an acute reduction of blood pressure when administered intravenously.

2. This is due entirely to a decrease in total peripheral vascular resistance.

3. On oral administration it can effectively lower blood pressure in mild hypertension and is effective in combination with other hypotensive agents with different mechanisms of action.
Deoxyribonucleic Acid Repair Synthesis: A new Factor for Defining High Blood Pressure
Authors: Thulin T. , Pero R. W. , Bryngelsson C. , Mitelman F. , Nordén Å. , Scherstén B.
Published: August 2015

1. The level of DNA repair synthesis has been compared in males diagnosed as having hypertension (diastolic blood pressure ≥ 100 mmHg), males with slightly elevated blood pressure (>95th percentile corrected for age) and males with normal or subnormal blood pressure (≤30th percentile corrected for age).

2. The hypertensive males and the males with elevated blood pressure could not be distinguished from each other with respect to the levels of chemically induced repair synthesis, but both were significantly increased over the induced repair synthesis values of individuals with normal or low blood pressure. Since it has been shown previously that lymphocytes with high repair synthesis values also have increased levels of both carcinogen-DNA binding and chromosomal aberrations (Nordén, Scherstén, Thulin, Pero, Bryngelsson & Mitelman, 1975), the biological significance of this variable appears to be of value in discriminating between normal and high blood pressure groups.
The Origin and Fate of Salivary Urea and Ammonia in Man
Authors: Kopstein J. , Wrong O. M.
Published: August 2015

1. Saliva obtained from the parotid duct of normal and uraemic subjects had an average urea concentration of 86% of the plasma concentration whereas in mixed saliva obtained from the mouth the urea concentration was only 31% of the plasma concentration. Ammonia concentrations were low or unmeasurable in parotid saliva but varied between 0·6 and 26 mmol/kg in oral saliva, showing a positive correlation with the plasma urea concentration.

2. The urea in samples of mixed oral saliva incubated at 37°C disappeared by 290 min. Ammonia steadily increased during incubation; within the first 100 min, the increase could be largely accounted for by bacterial hydrolysis of urea, but later non-urea sources became relatively more important.

3. These findings suggest that the ammonia in mixed oral saliva is derived by bacterial hydrolysis of urea within the mouth. However, the concentration of ammonia plus urea nitrogen in oral saliva was only 76% of the urea nitrogen concentration of parotid saliva, which suggests that some ammonia is lost from the mouth by buccal absorption or by volatilization.

4. To assess the role of non-ionic diffusion of ammonia through the buccal mucosa, we studied the effect of pH on the disappearance of ammonia from buffered solutions retained in the mouth. Ammonia concentrations fell more rapidly at pH 9 than at pH 7, as also did those of hydrazine, a non-volatile analogue of ammonia which is known to be absorbed through other mucosae by non-ionic diffusion. These findings suggest that salivary ammonia is reabsorbed passively through the oral mucosa in the un-ionized phase.
Blood Pressure Control in End-Stage Renal Disease in Man: Indirect Evidence of a Complex Pathogenic Mechanism besides Renin or Blood Volume
Authors: Cannella G. , Castellani A. , Mioni G. , Usberti M. , Guerra U. , Albertini A. , Maiorca R.
Published: August 2015

1. In twenty-three uraemic patients on regular dialysis, plasma renin activity and blood volume were measured before and after a single dialysis. Three groups were identified; the first had a low or normal plasma renin activity and a high or normal blood volume, the second had a high plasma renin activity and a low blood volume and the third had both variables above normal.

2. In spite of these differences, diastolic blood pressure before and after dialysis was the same in the three groups and multiple regression analyses failed to demonstrate any dependence of blood pressure on plasma renin activity, blood volume or body weight taken separately or together.

3. We conclude that other factors besides plasma renin activity and blood volume are important in maintaining arterial hypertension in terminal renal failure.
The Analysis of Decay Curves
Authors: Lafferty H. H. , Giddings A. E. B. , Mangnall D.
Published: August 2015

1. The limitations inherent in the conventional treatment of glucose decay curves as first-order rate systems are described.

2. The conventionally derived K value is a rate constant and should not be confused with a rate.

3. First-order systems are described by this rate constant and the initial concentration of substance studied. They cannot be described by either factor alone.

4. Two parallel curves cannot both result from first-order systems.

5. If K is conventionally calculated for two parallel curves, then the value obtained for the upper curve must be smaller than the value for the lower.
Release by Vasopressin of E-Type Prostaglandins from the Rat Kidney
Authors: Bell C. , Mya M. K. K.
Published: August 2015

1. In order to test whether the release of E-type prostaglandins from the kidney by various vasoconstrictor stimuli is related specifically to adrenoreceptor activation, we have compared release of prostaglandin E-like material from perfused rat kidneys during infusion of noradrenaline or vasopressin.

2. Concentrations of noradrenaline or vasopressin that produced comparable rises in renal perfusion pressure also released comparable amounts of prostaglandin E-like material. This effect was abolished by infusion of an inhibitor of prostaglandin synthesis into the kidney.

3. We conclude that liberation of E-type prostaglandins during renal vasoconstriction is probably related to the activation of intra-renal smooth muscle and does not involve any specific hormonal receptor. Stimulation of release of prostaglandin E may explain certain reported renal actions of vasopressin.