bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Moderate Salt Restriction and High Potassium Intake on Pressor Hormones, Response to Noradrenaline and Baroreceptor Function in Man
Authors: Skrabal F. , Aubouck J. , Hourtnagl H. , Braunsteiner H.
Published: August 2015

1. Twenty-one normotensive subjects were studied to assess any possible benefits of moderate salt restriction and of high potassium intake in the prevention of hypertension in man.

2. The effects of salt reduction from 200 to 50 mmol/day and/or of an increase of potassium intake from 80 to 200 mmol/day over a 2 week period, on blood pressure, plasma noradrenaline, adrenaline, vasopressin, renin and aldosterone, were measured both at rest and after mental stress. The effects of graded infusion of noradrenaline on blood pressure and heart rate were also studied.

3. Salt restriction lessened the increase of blood pressure during noradrenaline infusion; the combination with high potassium intake also reduced the pressure rise after mental stress. There were no major changes in plasma levels of vasopressin and adrenaline. Plasma noradrenaline increased during the low sodium diet.

4. High potassium intake improved baroreceptor function as revealed by the greater decrease in heart rate for a given rise in pressure after noradrenaline infusion.

5. The results of this study are compatible with a protective effect of a practicable low sodium/high potassium diet on the development of human hypertension.
Haemodynamics of Renoprival Hypertension in Man: Studies during Graded Fluid Withdrawal
Authors: Man in 'T Veld A. J. , Schalekamp M. A. D. H.
Published: August 2015

1. Frequent measurements of arterial pressure, cardiac output, heart rate and body weight were carried out in three hypertensive anephric subjects during the reversal of hypertension by carefully controlled stepwise fluid withdrawal over a period of 24 days.

2. The initial 5% decrease of body weight was associated with decrements of arterial pressure and total peripheral resistance of 15 and 35% respectively, whereas cardiac output had risen by 25%. After a further decrease in body weight by 5%, arterial pressure was lowered another 15% without a change in total peripheral resistance, and cardiac output had returned to base line.

3. These data do not support the concept that whole-body autoregulation is an important factor in the pathogenesis of renoprival hypertension.
Altered Cardiac β-adrenoreceptors in Spontaneously Hypertensive Rats Receiving Salt Excess
Authors: MacPhee A. A. , Blakesley H. L. , Graci Karen A. , Frohlich E. D. , Cole F. E.
Published: August 2015

1. Altered adrenergic responsiveness of hearts and blood vessels occurs in both experimental and clinical hypertension.

2. Since salt excess aggravates both types of hypertension, we investigated β-adrenoreceptor properties in the hearts of spontaneously hypertensive and normotensive rats drinking 1% NaCl or tap water for 3 weeks.

3. Sodium loading increased heart weight in both spontaneously hypertensive and normotensive rats.

4. In spontaneously hypertensive rats excess salt attenuated the age-related decrease in β-adrenoreceptor number observed in spontaneously hypertensive and normotensive rats drinking tap water and in normotensive rats drinking 1% NaCl.

5. Unlike the normotensive rats, which did not show a relationship between β-adrenoreceptor number and blood pressure, spontaneously hypertensive rats on tap water and 1% NaCl showed a significant negative logarithmic relationship between these two variables. These data provide further evidence implicating sodium excess as an aggravating factor in this model of experimental hypertension.
Effects of Variations in Sodium Intake on the Acute Vasodepressor Response to Kininase II Inhibition in Rats with Mild Two-Kidney, One-Clip Hypertension
Authors: Kushiro T. , Lee T. C. , Girolami J. P. , Gassia J. P. , Maxwell M. H.
Published: August 2015

1. Unilateral renal artery constriction in rats maintained on a sodium-deplete, but not sodium-replete, diet induced an augmented acute vasodepressor response to kininase II inhibition produced by an intravenous injection of the dipeptidyl carboxypeptidase inhibitor captopril (250 μg) during continuous saralasin-induced angiotensin II blockade (10 μg/min). Dietary sodium restriction alone in sham-operated rats had no effect.

2. Acute bilateral adrenalectomy (18-24 h) did not preclude the demonstration of an augmented response to kininase II inhibition in sodium-depleted rats with benign two-kidney, one-clip hypertension. Neither did chronic administration of deoxycorticosterone acetate in intact rats elicit an augmented response.

3. The augmented acute vasodepressor response to kininase II inhibition in sodium-depleted rats with benign two-kidney, one-clip hypertension is probably due to bradykinin potentiation and secondary to an increased activity of the kallikrein-kinin system. The mechanism responsible for this apparent increase is not known, but neither hyperangiotensinemia nor hyperaldosteronism seems to play a role.
Vascular Sodium—Potassium Pump Activity in Various Models of Experimental Hypertension
Authors: Pamnani M. B. , Clough D. L. , Huot S. J. , Haddy F. J.
Published: August 2015

1. Ouabain-sensitive 86Rb uptake was used to assess sodium-potassium pump activity in vascular smooth muscle of animals with various types of experimental hypertension.

2. The findings suggest that pump activity is suppressed in the non-genetic low renin, presumably volume-expanded forms of hypertension.

3. By contrast, pump suppression does not appear to be involved in spontaneously hypertensive rats or in salt-induced hypertension in Dahl's salt-sensitive rats. In these genetic models the primary defect may be increased cell membrane permeability.
Increased Pressor Responsiveness to Enkephalin in Spontaneously Hypertensive Rats: The Role of Vasopressin
Authors: Rockhold R. W. , Crofton J. T. , Share L.
Published: August 2015

1. The cardiovascular effects of an enkephalin analogue were examined in spontaneously hypertensive and normotensive Wistar-Kyoto rats. (D-Ala2)-methionine enkephalin caused a biphasic increase in blood pressure and an increase in heart rate after intracerebroventricular injection.

2. The initial pressor response to (D-Ala2)-methionine enkephalin was greater in hypertensive than in normotensive rats. No difference was noted between groups during the secondary pressor response. Heart rate increases paralleled the secondary increase in blood pressure.

3. Naloxone pretreatment abolished the secondary increase in blood pressure and the tachycardia, but did not blunt the initial pressor response in female Wistar-Kyoto rats.

4. Plasma levels of arginine vasopressin were depressed during the plateau phase of the pressor response in hypertensive rats given intracerebroventricular (d-Ala2)-methionine enkephalin.

5. The results suggest that the cardiovascular effects of central enkephalin are not due to vasopressin, but may involve activation of the sympathetic nervous system.
Determination of Noradrenaline Uptake, Spillover to Plasma and Plasma Concentration in Patients with Essential Hypertension
Authors: Esler M. , Jackman G. , Leonard P. , Bobik A. , Skews Helen , Jennings G. , Kelleher Dianne , Korner P.
Published: August 2015

1. The rates of entry of noradrenaline to plasma and of removal of noradrenaline from plasma, and plasma noradrenaline concentration, were determined in normal subjects and in patients with essential hypertension. Neuronal uptake of noradrenaline was assessed from the plasma tritiated noradrenaline disappearance curve, after infusion to steady state.

2. Noradrenaline disappearance was biexponential. Rapid removal was dependent on neuronal uptake, being slowed if neuronal noradrenaline uptake was reduced, either by desipramine in normal subjects, or in patients with sympathetic nerve dysfunction (autonomic insufficiency).

3. In 10 of 41 hypertensive patients the t1 1/2 similarly was prolonged, presumptive evidence of a defect in neuronal noradrenaline uptake. Endogenous noradrenaline escaping uptake after release, and spilling over into plasma, and plasma noradrenaline concentration, were increased in these patients.

4. Defective neuronal uptake of noradrenaline, by exposing adrenoreceptors to high local transmitter concentration, may be important in the pathogenesis of essential hypertension in some patients.
Is Arterial Media Hypertrophy in Spontaneously Hypertensive Rats a Consequence of or a Cause for Hypertension?
Authors: Henrichs K. J. , Unger T.H. , Berecek K. H. , Ganten D.
Published: August 2015

1. The increased peripheral resistance observed in established hypertension has been attributed to structural changes in the resistance vessels, which are considered to be due mainly to medial hypertrophy. This study was undertaken to examine the possiblity that structural changes in the arterial bed are genetically determined and may be causative factors in the development of high blood pressure in the spontaneously hypertensive rat.

2. The wall dimensions of aorta, renal artery and intrarenal arteries down to a distended diameter of 35 μm were studied: (a) in 14-week-old spontaneously hypertensive rats; (b) in age- and sex-matched spontaneously hypertensive rats which had been treated with captopril for two generations and had been normotensive during their complete life span; (c) in normotensive Wistar-Kyoto control rats.

3. Cross-sectional areas of the media were increased in the hypertensive rats in comparison with ‘normotensive spontaneously hypertensive rats’ and Wistar-Kyoto rats. Increased numbers of smooth muscle cells were found in the major arteries of hypertensive animals.

4. These results indicate that hypertrophy of the media is a consequence of high blood pressure rather than a genetically determined pathogenetic factor for the development of hypertension in spontaneously hypertensive rats.
Cardiac Contractile Reserve in Spontaneously Hypertensive Rats
Authors: Saragoca M. A. , Tarazi R. C.
Published: August 2015

1. In response to graded infusions of isoprenaline, adult spontaneously hypertensive rats (20-24 weeks old) showed diminished responses of left ventricular contractile indices, diminished chronotropic responses and impairment of left ventricular relaxation rate as compared with matched Kyoto-Wistar rats.

2. These findings suggest reduced capacity to increase contractility in response to stress.
Myocardial Infarction in Experimental Hypertension in Rats: Mechanism of the Reduction in Blood Pressure
Authors: Fletcher P. J. , Pfeffer Janice M. , Pfeffer M. A. , Braunwald E.
Published: August 2015

1. Haemodynamic changes during graded methoxamine infusion have been measured in 16 spontaneously hypertensive rats with healed myocardial infarction produced by left coronary artery ligation and in 15 hypertensive rats without infarction.

2. Arterial pressure of the hypertensive rats was reduced to levels within the normotensive range in animals with moderate and large myocardial infarctions.

3. The peripheral vascular response to methoxamine was similar in rats with and without infarction.

4. The reduction in blood pressure resulted from a combination of lower heart rate and inability to maintain stroke volume at hypertensive pressures.
Left/Right Ventricular Weight Ratio: An Estimate of ‘Cardiac Adaptation to Hypertension’
Authors: Hallbauck-Nordlander Margareta
Published: August 2015

1. Left and right ventricular weights were determined in newborn, 6, 15 and 28 week-old spontaneously hypertensive and normotensive control rats.

2. Left and right ventricles were heavier in all spontaneously hypertensive rats than in age-matched control rats, but the left/right ventricular weight ratio was increased only in 15 and 28 week-old spontaneously hypertensive rats.

3. If the cardiomegaly in newborn spontaneously hypertensive rats, in which the two ventricles have worked in parallel until birth, is an adaptation to hypertension in utero, left ventricular weight would rapidly increase after birth as the left ventricle alone is then exposed to an increased pressure. As left/right ventricular weight ratio was not increased in 6 week-old spontaneously hypertensive rats, factors other than hypertension may stimulate cardiac growth in the foetal spontaneously hypertensive rat.

4. This implies an initial structural ‘resetting’ of the cardiovascular dimensions in spontaneously hypertensive rats and that true pressure-dependent adaptation further potentiates these alterations in cardiovascular structure once hypertension is initiated.
Effect of Blood Pressure Control on Left Ventricular Hypertrophy in Patients with Essential Hypertension
Authors: Dunn F. G. , Bastian B. , Lawrie T. D. V. , Lorimer A. R.
Published: August 2015

1. Changes in left ventricular structure and function were assessed by echocardiography in 22 patients before and after 9 months blood pressure control.

2. Nine patients had normal baseline echocardiograms (group 1) and 13 had echocardiographic evidence of left ventricular hypertrophy (group 2).

3. Group 2 patients demonstrated significant reductions in posterior wall thickness (P<0.01), septal wall thickness (P<0.025) and left ventricular mass (P<0.005). Only six of the 13 patients showed a reduction of ≥3 mm in posterior wall thickness. The remainder showed no alteration or only a slight non-significant reduction.

4. The regression of voltage in some patients but not in others did not appear to be related to initial blood pressure, the extent of the fall in blood pressure or duration of follow-up. It was not possible to say whether any specific therapy was beneficial to regression since most of the patients were on multiple therapy.
Hydrallazine: Mode of Action at the Neuroarterial Junction
Authors: Chevillard C. , Saiag B. , Worcel M.
Published: August 2015

1. Hydrallazine relaxes the rat tail artery by a direct action on vascular smooth muscle cells, which appears to be modulated by the action of sympathetic nerve terminals.

2. There is a gradient of response to hydrallazine in arteries from normotensive Wistar rats, the proximal segments being poorly responsive. This gradient disappears after denervation with 6-hydroxydopamine in vitro.

3. Exogenously added purines inhibit noncompetitively the vasodilator response to hydrallazine in denervated segments from normotensive Wistar rats. Their order of potency is 2-Cl-adenosine > adenosine > ATP > inosine.

4. The effect of hydrallazine in innervated, poorly responsive segments is greatly potentiated by theophylline (50 μmol/l) and propranolol (5 μmol/l). These results, together with the effect of denervation, suggest that there are endogenous purines leaking from the nerve terminals under our experimental conditions.

5. Hydrallazine produces a marked inhibition of stimulus-induced contraction and 3H release after [3H]noradrenaline loading. The mechanism of this prejunctional action appears to be different from the mechanism of the postjunctional effect.
Comparison of Ventilation/Perfusion Lung-Imaging and Dead-Space Measurements in Airway Disease
Authors: Noble M. I. M. , Langley F. , Buckman M. , Vernon P. , Seed A. , Jewkes R. , Bisdee A. , Cumming G.
Published: August 2015

1. Nineteen patients (three normal subjects, and 16 patients with chronic airway disease) were investigated with radionuclide lung-imaging and pulmonary function tests.

2. There was a statistically significant correlation between the ratio of residual volume to total lung capacity and alveolar dead-space ventilation for nitrogen as a percentage of alveolar ventilation (an index of gas mixing inefficiency); rS = 0.54, P < 0.05.

3. There were statistically significant associations between an abnormal ventilation or perfusion radionuclide lung image and (a) the ratio of residual volume to total lung capacity and (b) the alveolar dead-space ventilation for nitrogen as a percentage of alveolar ventilation.

4. The radionuclide counts from the posterior images were normalized for lung size and injected dose; perfusion counts were then subtracted from ventilation counts at locations from the top to the bottom of the lungs.

5. There was a statistically significant association between low ventilation minus perfusion areas and arterial hypoxia.

6. There was a statistically significant association between high ventilation minus perfusion areas and an increased alveolar dead-space ventilation for carbon dioxide as a percentage of alveolar ventilation.
The Effect of Prolonged Administration of Propranolol and Timolol on the Growth and the Heart of Growing Rabbits
Authors: Evemy K. L. , Cummins P. , Littler W. A.
Published: August 2015

1. The effect of prolonged administration of β-adrenoreceptor-blocking agents was studied in growing rabbits. Equivalent doses of propranolol and timolol were given parenterally for 8 weeks.

2. Animals given propranolol had a significantly lower heart rate than that in the controls. After subcutaneous injection, plasma propranolol levels were twice those obtained after intraperitoneal injection.

3. Growth rate of animals given propranolol intraperitoneally was significantly less than controls, whereas animals given propranolol subcutaneously or timolol intraperitoneally grew normally. Reduced growth rate was associated with reduced food intake and was not related to the β-adrenoreceptor-blocking activity of the drugs.

4. At the end of the experiment the heart and other organs were examined. β-Adrenoreceptor blockade produced no significant changes in ventricular size or water content, and no significant changes in ultrastructure were found.
Clearance of Fibrin from Glomeruli. Renal Cortical Fibrinolytic Response after Thromboplastin Infusion in the Rat
Authors: Sanchez-Ibarrola A. , Qazzaz S. , Naish P.
Published: August 2015

1. The time sequence of glomerular fibrin deposition, renal cortical fibrinolytic response and thrombocytopenia after thromboplastin infusion in rats has been established.

2. Fibrin clearance is rapid and is associated with markedly increased cortical fibrinolytic activity.

3. Plasma fibrinolytic activity was unchanged.

4. Experiments in which the dose-response relationship between thromboplastin dose, fibrin deposition and fibrinolytic response was examined showed that fibrinolytic response increased with fibrin deposition in glomeruli.

5. The dose—response experiments also provided data which suggested that the method of measurement of cortical fibrinolytic activity in the presence of deposited fibrin measures excess rather than total plasminogen activator production.
Comparison of Radioisotope Methods for the Measurement of Phosphate Absorption in Normal Subjects and in Patients with Chronic Renal Failure
Authors: Farrington K. , Mohammed M. N. , Newman S. P. , Varghese Z. , Moorhead J. F.
Published: August 2015

1. Intestinal phosphate absorption was measured in normal subjects, in patients with chronic renal failure, and in post-transplant patients, by a double isotope technique involving oral administration of 32P and simultaneous intravenous injection of 33P with subsequent deconvolution analysis.

2. By this technique intestinal phosphate absorption has been shown to have two components: an initial rapid phase, which is completed by 3 h, and a slower more prolonged phase, which continues beyond 7 1/2 h.

3. Phosphate malabsorption has been demonstrated in chronic renal failure and transplant patients, which is accounted for by impairment of the initial rapid phase of absorption.

4. Results obtained by deconvolution analysis have been compared with other estimates of phosphate absorption obtained from analysis of 32P radioactivity curves alone.

5. The fractional hourly rate of absorption and the plasma 32P radioactivity at 60 min corrected for extracellular fluid volume provided the best approximations to the result obtained by deconvolution analysis, with respect to both the maximal rate of phosphate absorption and cumulative percentage phosphate absorption.
Human Saliva and Semen: Evidence for Proteins Common to Both Which Do Not Occur in Serum
Authors: Eckersall P. D. , Beeley J. A.
Published: August 2015

1. Rabbit antiserum to human whole saliva cross-reacts with both human serum and semen. After absorption of the antiserum by affinity chromatography on a column of immobilized serum protein, the cross-reactions with serum were eliminated.

2. The absorbed antiserum, however, still cross-reacted with semen thus indicating the presence of proteins with immunological similarity in both saliva and semen, but which did not occur in serum.

3. Some of these proteins clearly showed a reaction of complete immunological identity between saliva and semen.

4. The presence of the non-serum proteins in both saliva and semen might be related to common functions in both such as lubrication or antibacterial activity.
Effect of Acute and Chronic Alcohol Ingestion on the Rate of Folate Catabolism and Hepatic Enzyme Induction in Mice
Authors: Kelly D. , Reed B. , Weir D. , Scott J.
Published: August 2015

1. Folate deficiency is commonly found in alcoholic subjects although the causative mechanism is uncertain. It has been suggested that microsomal enzyme induction resulting from chronic alcohol ingestion might accelerate the rate of folate catabolism thus causing deficiency.

2. By using an experimental animal model to determine the rate of catabolism of [3H]pteroylglutamate (folic acid) by the quantitative estimation of the two urinary catabolites p-[3H]aminobenzoylglutamate and [3H]acetamidobenzoylglumate, we have measured both the rate of folate catabolism and the extent of microsomal-enzyme induction in mice after acute and chronic alcohol ingestion.

3. Despite significant evidence of enzyme induction in the chronic alcohol group, there was no difference in the rate of folate catabolism after acute or chronic alcohol ingestion when compared with that of the controls.
Effect of Chronic and Acute Changes in Sodium Balance on the Urinary Excretion of Prostaglandins E2 and F2α in Normal Man
Authors: Rathaus M. , Podjarny E. , Weiss Eli , Ravid M. , Bauminger Sara , Bernheim J.
Published: August 2015

1. The effects of changes in sodium balance on renal prostaglandins have been hitherto studied mainly in experimental animals and the results have been controversial. In this study the 24 h urinary excretion of prostaglandins E2 and F2α was measured by radioimmunoassay in seven normal subjects under basal conditions and after 5 days of a diet containing <20 mmol of sodium/day. Subsequently a sodium chloride (150 mmol/l: saline) load (300 mmol of sodium over 4 h) was infused and prostaglandins were again measured in hourly urine collections. Plasma renin activity and aldosterone were also measured under basal conditions, after the low sodium diet and at 2 and 4 h of the saline infusion.

2. Dietary sodium restriction was associated with a marked increase in prostaglandin E2 excretion (from 769.7 ± 201.6 sem to 1761.3 ± 304.9 ng/24 h, P<0.0005). Prostaglandin F2α also increased from 1187.0 ± 390.1 to 1435.6 ± 344.6 ng/24 h, but this was not statistically significant. The prostaglandin E2/prostaglandin F2α ratio increased from 0.83 ± 0.2 to 1.52 ± 0.34 (P<0.01). Plasma renin activity and aldosterone rose significantly (P<0.05 and<0.0025 respectively).

3. During the saline load prostaglandin E2 decreased after 2 h from 142.4 ± 29.9 to 86.7 ± 22.9 ng/h (P<0.05) and to 36.9 ± 5.96 ng/h after 4 h. Prostaglandin F2α decreased at a slower rate, from 98.4 ± 18.7 to 37.5 ± 8.8 ng/h at 4 h (P<0.02). At 4 h the prostaglandin E2/prostaglandin F2α ratio returned to control values (0.90 ± 0.17). Plasma renin activity and aldosterone decreased significantly after 2 h (P<0.02 and<0.0025 respectively) and reached control values after 4 h.

4. The present study demonstrates that chronic and acute changes in sodium balance induce changes in the excretion of prostaglandin E2 parallel to changes in plasma renin activity and aldosterone. The similar but quantitatively smaller changes in prostaglandin F2α and the inversion of the ratio between the two prostaglandins during sodium deprivation suggest that at least two factors are involved: increased delivery of substrate for prostaglandin synthase and decreased activity of the prostaglandin E2 9-ketoreductase. Prostaglandins probably play an important role in the adaptation of the kidney to changes in sodium balance.
Effect of Chronic Dietary Potassium Depletion and Repletion on Cardiac and Skeletal Muscle Structure, Electrolytes and pH in the Rabbit
Authors: Hall R. J. C. , Cameron I. R.
Published: August 2015

1. Chronic dietary potassium depletion which was severe enough to decrease skeletal muscle intracellular potassium concentration by 20%, did not significantly reduce cardiac intracellular potassium concentration of rabbits.

2. Chronic potassium depletion caused a fall in intracellular pH in skeletal muscle, but no changes occurred in cardiac intracellular pH.

3. Intracellular potassium was increased above normal after 1 week of potassium repletion, but had returned to normal after 3 weeks of repletion. This may have resulted from potassium retaining mechanisms which had developed during depletion and which persisted during the early stages of repletion.

4. Cardiac and skeletal muscle from potassium-depleted animals did not show any structural damage when examined by light and electron microscopy.
Inner Medullary Osmolality and Sodium Concentration are Decreased in Rats during Escape from DOCA-Induced Salt Retention
Authors: Düsing R. , Wilke R. , Körber A. , Klingmüller D. , Kramer H. J.
Published: August 2015

1. Papillary osmolality and sodium and potassium concentrations were determined in rats during a control period and during escape from the sodium-retaining effect of deoxycorticosterone acetate and compared with the changes observed after acute frusemide injection.

2. During escape, papillary osmolality [554 ± 36 vs 754 ± 42 mmol/kg of papillary water (H2O), P<0.005] and papillary sodium concentration (131 ± 7 vs 182 ± 8 mmol/kg H2O, P<0.001) were significantly decreased as compared with the control values, while papillary potassium concentration remained unchanged.

3. Frusemide decreased papillary osmolality to 538 ±41 mmol/kg H2O (P<0.005), papillary sodium concentration to 125 ± 9 mmol/kg H2O (P<0.001) and papillary potassium concentration from 80 ± 2 to 69 ± 3 mmol/kg H2O (P<0.05).

4. The present results suggest that medullary portions of the distal tubule (probably the ascending loop of Henle) may represent one site of tubular sodium chloride rejection during escape from the sodium-retaining effect of deoxycorticosterone acetate.
Renin Response to Volume Contraction and Indomethacin in Spontaneously Hypertensive Rats
Authors: Cangiano J. L. , Rodriguez-Sargent Carmen , Nascimento L. , Martinez-Maldonado M.
Published: August 2015

1. The effects of volume contraction and indomethacin on renin response were examined in spontaneously hypertensive rats and Wistar-Kyoto normotensive rats. Volume contraction was induced by frusemide or by salt-restricted diet combined with frusemide administration.

2. Plasma renin levels were not altered by either procedure in spontaneously hypertensive rats (5.2 ± 0.8 versus 5.6 ± 0.9 ng h−1 ml−1). Normotensive rats responded to volume contraction with a sharp increase in plasma renin activity (13.1 ± 1.2 to 23.3 ± 1.1 ng h−1 ml−1).

3. Intraperitoneal injection of indomethacin for 1 week did not alter basal renin levels in either group. In contrast, indomethacin pretreatment caused renin to rise in response to frusemide in spontaneously hypertensive rats (4.7 ± 0.8 to 27.1 ± 1.8 ng h−1 ml−1).

4. These findings suggest that a prostaglandin normally inhibits the renin response of spontaneously hypertensive rats to frusemide-induced volume contraction. Inhibition of prostaglandin synthesis allows volume contraction to stimulate renin release.
Captopril Combined with Thiazide Lowers Renin Substrate Concentration: Implications for Methodology in Renin Assays
Authors: Rasmussen S. , Nielsen M. Damkjaer , Giese J.
Published: August 2015

1. We have measured plasma concentrations of renin, renin substrate and angiotensins I and II as well as plasma renin activity in nine patients with severe or malignant hypertension during treatment with captopril, hydrochlorothiazide and propranolol.

2. On captopril and hydrochlorothiazide the plasma concentrations of renin substrate and angiotensin II decreased markedly, while renin and angiotensin I levels were increased.

3. The changes in renin substrate concentration suggest a consumption of substrate induced by an increased renin release. Further, the positive feedback of angiotensin II on hepatic renin substrate synthesis may be inhibited.

4. The sequential changes in renin release during captopril treatment should be monitored by measuring plasma renin concentration since plasma renin activity measurements will be profoundly influenced by the marked changes in plasma renin substrate concentration.
Proteinase Activity of Human Renin Preparations: The International Reference Preparation (Renin Standard 68/356)
Authors: Pourmotabbed G. , Chou H. J. , Workman R. J. , Gregerman R. I.
Published: August 2015

1. Several commonly used preparations of human renin, including the International Reference Preparation (Renin Standard 68/356), were examined for the presence of contaminating proteinase activity by using a 14C-glycinated bovine haemoglobin substrate assay.

2. All of the human renin preparations tested cleaved haemoglobin even in the presence of di-isopropylfluorophosphate and ethylenediaminetetra-acetate (EDTA). For a given amount of renin activity, varying amounts of proteinase activity were seen. The pH optimum also varied between preparations.

3. Small peptide inhibitors of human renin were not able to inhibit the proteinase activity. Furthermore a diazoacyl reagent and pepstatin, both potent inhibitors of aspartic acid-active site proteinases, were only partially inhibitory.

4. These and other observations suggest that the proteinase activity of the human renin preparations is not due to renin itself, but to contaminating proteinases of different types. Since these enzymes may produce angiotensin I or peptides which may interfere in renin assays, crude preparations of renin which contain proteinase activity, including the International Reference Preparation, should be used with caution or replaced by proteinase-free human renin which can be easily prepared by use of suitable affinity chromatography.
Properties of a Renin Inhibitor Isolated from the Pig Kidney Cortex
Authors: Sagnella G. A. , Peart W. S.
Published: August 2015

1. A renin-inhibitory material has been partially purified from soluble extracts of the pig kidney cortex by ammonium sulphate precipitation and diethylaminoethylcellulose (DEAE) chromatography and its properties studied.

2. It displayed competitive type kinetics. It did not inhibit cathepsin D, carboxypeptidase A, pancreatic kallikrein or trypsin.

3. Renins from dog, rabbit and rat were inhibited, but not those from sheep or man, when assayed with pig angiotensinogen.

4. The material was inactivated by treatment with trypsin, N-ethylmaleimide or p-chloromercuribenzoate.

5. Renin-inhibitory activity was not found in plasma from peripheral blood of pigs.

6. It is concluded that the function of the renin inhibitor in the renal cortex of the pig may be restricted to the intrarenal environment.
Effect of Hyperprolactinaemia Due to Pituitary Tumour on Serum Albumin, Protein and Oncotic Pressure
Authors: Brajkovich I. E. , De Leon R. S. , Mashiter K.
Published: August 2015

1. Serum albumin, total protein, oncotic pressure and osmolality were measured in a group of patients with hyperprolactinaemia due to a prolactin secreting tumour, normal subjects and normoprolactinaemic acromegalic patients.

2. A significant increase in albumin, total protein and oncotic pressure was found in the prolactinoma patients when compared with those of the other two groups.

3. There was no difference in serum osmolality between the three groups.

4. These studies provide further evidence that prolactin may have anabolic effects.
Proteins in the Urine Associated with Duchenne Muscular Dystrophy and other Neuromuscular Diseases
Authors: Frearson N. , Taylor R. D. , Perry S. V.
Published: August 2015

1. Up to 200 protein staining spots could be detected on two-dimensional electrophoresis of urine from healthy persons. Other minor spots were occasionally present.

2. Although the electropherograms exhibited constant characteristic features some variation in protein pattern was observed between individuals and with a given individual at different times.

3. Two additional proteins, spots C and D, were consistently present in urine from boys with Duchenne muscular dystrophy. Spot C was also present in the urine of about 60% of obligatory carriers of this dystrophy.

4. The protein responsible for spot C had a molecular weight of 26000 and an isoelectric point of 5.3.

5. Spot C was also detected in the urine of patients with other neuromuscular conditions. Neither spot C nor spot D could be detected in the urine of patients with physical disabilities other than those of neuromuscular origin.

6. It is concluded that the urinary excretion of spot C, and probably of spot D, is a consequence of muscle damage and that their detection has potential as a diagnostic tool.
Increased Intralymphocytic Sodium Content in Essential Hypertension: An Index of Impaired Na+ Cellular Metabolism
Authors: Ambrosioni E. , Costa F. V. , Montebugnoli L. , Tartagni F. , Magnani B.
Published: August 2015

1. The sodium concentration in lymphocytes was measured in a group of 66 normotensive subjects (40 without familial hypertension and 26 with familial hypertension), in a group of 81 patients with essential hypertension and in a group of 14 patients with secondary hypertension.

2. The mean value (±sd) in normotensive subjects with no history of familial hypertension was 21.9 ± 3.1 mmol/kg wet weight, which was significantly lower (P < 0.005) than that of normotensive subjects with familial hypertension (mean value 27.9 ± 4.2 mmol/kg). Lymphocyte sodium concentration was significantly higher in patients with essential hypertension (33.2 ± 3.3 mmol/kg; P < 0.001) than in the subjects with normal blood pressure without familial hypertension.

3. In the patients with essential hypertension there was a significant correlation between lymphocyte sodium concentration and systolic (P < 0.005), diastolic (P < 0.001) and mean (P < 0.001) blood pressure. In the normotensive subjects there was no correlation between the lymphocyte sodium concentration and the blood pressure.

4. The patients with secondary forms of hypertension had normal lymphocyte sodium concentration, except in the case of Conn's disease.

5. Incubation with ouabain increased lymphocyte sodium concentration in the normotensive subjects and patients with essential hypertension; the final sodium concentration was similar in the two groups.

6. When lymphocytes from normotensive subjects without familial hypertension were incubated in plasma of patients with essential hypertension there was an increase in their sodium content.
Effect of Hypertonic and Hypotonic Infusions on Aldosterone in Conscious Sodium-Depleted Dogs
Authors: Childers Jennifer W. , Schneider E. G.
Published: August 2015

1. The role of the plasma sodium concentration in the regulation of aldosterone secretion and sodium excretion was investigated by comparing in 13 conscious sodium-depleted dogs the effects of the same sodium load (2.5 mmol/kg) given as either a hypertonic or hypotonic infusion.

2. The plasma sodium concentration was significantly higher and the plasma aldosterone concentration and urinary aldosterone excretion were significantly lower after the hypertonic infusion as compared with the hypotonic infusion.

3. The cumulative urinary sodium excretion during the 22 h after beginning the infusion was significantly greater after the hypertonic infusion, but this difference was not observed in five sodium-depleted dogs who were treated with deoxycorticosterone acetate before the infusions were given.

4. These data suggest that elevations in plasma sodium concentration are effective in decreasing aldosterone secretion and, hence, in increasing sodium excretion in conscious sodium-depleted dogs.
Relationship between Plasma High-Density Lipoprotein Concentrations and Lipoprotein Lipase and Hepatic Lipase Activities in Children with Hyperlipidaemia
Authors: Gamlen T. R. , Layward E. , McTaggart F. , Muller D. P. R.
Published: August 2015

1. Significant positive correlations were found between the lipoprotein lipase and hepatic lipase activities of post-heparin plasma samples and plasma high-density-lipoprotein (HDL) cholesterol concentrations in 21 children with hyperlipidaemia and six normal adult males.

2. A significant positive correlation was also observed between the two lipase activities and the ratio of HDL cholesterol to apoprotein AI (apo AI) concentrations.

3. These findings provide further evidence that a significant proportion of HDL and possibly the HDL2 subfraction is formed during the clearance of triglyceride-rich lipoproteins.
Detection and Interaction of Elastic and Flow-Resistive Respiratory Loads in Man
Authors: Shahid S. U. , Goddard B. A. , Howell J. B. L.
Published: August 2015

1. The detection of added inspiratory airflow resistances was studied in normal individuals under two circumstances: first, while breathing unhindered, and secondly, while breathing against continuously applied (‘basal’) inspiratory elastic loads. The addition of basal elastic loads resulted in impaired detection of flow-resistive loads whether expressed as added flow resistance or as a proportion of the basal flow resistance.

2. When loads were plotted on a logarithmic scale, load-detection relationships were linear, permitting both threshold and slope of the detection response (‘sensitivity’) to be assessed. Impaired detection associated with basal elastic loads was shown to be due to a raised threshold without change in ‘sensitivity’.

3. When the flow resistances submitted for detection were expressed as a proportion of the sum of the basal flow resistance and added elastance, the probability of detection was independent of the magnitude of the added elastance.

4. The interaction between basal elastic and added flow-resistive loads suggests that at the time of detection the basal elastance acts in a manner similar to that of an added flow resistance.

5. Added basal flow resistances had no significant effect on the detection of threshold elastic loads.
Heart Rate Variability in Healthy Subjects Measured with a Bedside Computer-Based Technique
Authors: Smith S. E. , Smith S. A.
Published: August 2015

1. A computer-based technique is described for measuring and analysing cardiac beat-to-beat intervals.

2. The R-R intervals were recorded at rest, during forced deep breathing and during the Valsalva manoeuvre in 174 healthy subjects aged between 16 and 89 years.

3. The mean resting R-R interval was independent of sex, age and smoking habit. The normal range was 654.6-1141.4 ms with a mean value of 864.7 ms.

4. Variation in interval length at rest and during deep breathing depended on age and the mean interval length, whereas the Valsalva ratio depended on age alone. Normal ranges were calculated from regression analysis of these relationships.

5. It is concluded that the technique described can be used to test cardiac autonomic function at the bedside.
Evidence for Inhibitory and Anti-Ouabain-Like Factors in Leukaemic Blood
Authors: Mir M. A.
Published: August 2015

1. At a high dilution in Ringer solution (1:200), leukaemic plasma significantly (P < 0.05) decreased the ouabain-sensitive and increased ouabain-insensitive components of sodium efflux from erythrocytes. At a low dilution (1:10) leukaemic plasma predominantly decreased the total and ouabain-insensitive component of sodium efflux (P < 0.01).

2. Erythrocytes from patients with leukaemia had a high affinity for the plasma factor which inhibited the total and ouabain-insensitive efflux (inhibitory factor).

3. Washings of leukaemic erythrocytes which had been incubated in leukaemic plasma contained a factor which significantly decreased the ouabain-sensitive and increased ouabain-insensitive components of sodium efflux (the anti-ouabain-like factor).

4. These studies show that leukaemic blood contains two factors which have opposite effects on sodium efflux from erythrocytes. These factors may contribute to the high incidence of multiple electrolyte disturbances in acute myeloid leukaemia.
Circulating Dopamine: Its Effect on the Plasma Concentrations of Catecholamines, Renin, Angiotensin, Aldosterone and Vasopressin in the Conscious Dog
Authors: Ball S. G. , Tree M. , Morton J. J. , Inglis G. C. , Fraser R.
Published: August 2015

1. Six male beagle dogs with carotid loops were infused with sodium chloride solution (150 mmol/l: saline) during control observations followed by dopamine infusion at various rates. Arterial blood samples were drawn during the control period and at the end of each period of dopamine infusion for the measurement of plasma dopamine, noradrenaline, adrenaline, renin, angiotensin II, aldosterone, vasopressin, electrolytes and packed cell volume. Blood pressure and pulse were recorded throughout.

2. The rate of infusion and plasma dopamine levels were closely correlated (r = 0.99, P < 0.001). Plasma dopamine levels two to 20 times basal values produced no significant change in any of the other variables measured; levels 200 times basal values caused a significant increase (P < 0.05) in plasma renin concentration; levels 2000 times basal values were associated with significant increases (P < 0.05) in plasma renin and angiotensin II, packed cell volume and blood pressure, without significant changes in other measurements.

3. Circulating dopamine is unlikely to be important in the control of sodium and water metabolism.
Measurement of Hypozincaemia in Mice: A Sensitive Test for Detection of Pyrogens
Authors: Boobis Susan , Hartley Rose E.
Published: August 2015

1. The effect of bacterial pyrogens on plasma zinc concentration in mice was studied as a method of bioassay for these substances.

2. A dose-related depression of plasma zinc concentrations was observed 4 h after intravenous injection of doses of 0.05-500 ng of purified endotoxins of Salmonella abortus equi, Shigella dysenteriae and Escherichia coli. Responses were dose-dependent and reproducible for each endotoxin in five strains of mice.

3. Tolerance to endotoxin could be induced in mice by injection of doses of 500 ng but was not seen with doses of <5 ng, even after repeated treatment.

4. Dinitrophenol, a metabolic inhibitor, and amphetamine, a metabolic enhancer, did not affect plasma zinc levels, indicating that changes in basal metabolic rate do not affect the outcome of this assay. The effects of pyrogenic materials other than endotoxin on plasma zinc levels were also tested and the results suggest that measurement of hypozincaemia in mice provides the basis for a simple, practical and inexpensive test for endotoxins and other pyrogens.
Hypoglycaemia, Hypothermia and Shivering in Man
Authors: Gale E. A. M. , Bennett T. , Green J. Hilary , MacDonald I. A.
Published: August 2015

1. The present experiments were designed to elucidate the reasons for the fall in central body temperature during hypoglycaemia.

2. The first experiment was carried out at a room temperature of 25 °C on 11 male subjects. Hypoglycaemia was induced by infusion of insulin. Heat production (calculated from respiratory gas exchange) rose from a baseline of 5.10 ± 0.13 kJ/min (mean ± sem) to a peak of 6.25 ± 0.21 kJ/min (P < 0.001), but core temperature fell concurrently by 0.51 ± 0.08°C and skin temperature fell by 1.1 ± 0.2°C. The net heat loss was due to peripheral vasodilatation and sweating.

3. To determine the effect of insulin-induced hypoglycaemia on thermoregulation in a cool environment, the experiment was repeated at a room temperature of 18–19°C on five of the subjects who had air blown over them until shivering was sustained. During this time heat production rose to 10.13 ± 1.67 kJ/min, but core temperature remained constant. Shivering stopped as plasma glucose fell below 2.5 mmol/l during insulin infusion and the subjects said they no longer felt cold.

4. During hypoglycaemia in the cold peripheral vasodilatation and sweating occurred, skin temperature fell by up to 0.8°C and core temperature fell below 35°C, so subjects had to be rewarmed.

5. Recovery of plasma glucose after hypoglycaemia in the cold was impaired at low body temperatures, but shivering was restored within seconds when glucose was given intravenously.
Mechanical Properties and Reactivity of Vessels in Isolated Perfused Lungs of Chronically Hypoxic Rats
Authors: Emery Celia J. , Bee Denise , Barer Gwenda R.
Published: August 2015

1. Chronically hypoxic rats kept in 10% (v/v) O2 for 3–6 weeks, were compared with littermate control rats. Pulmonary vascular resistance, measured from the slope of the pressure-flow relationship in isolated lungs perfused with blood of normal packed cell volume was higher in chronically hypoxic than control rats even during normoxia.

2. Chronically hypoxic rats weighed less than control rats but their pulmonary vascular volume, measured with labelled albumin was similar to control rats. This, together with evidence that the number of precapillary vessels is not reduced, does not suggest a large reduction in the vascular bed in chronic hypoxia.

3. A greater vasodilator action of isoprenaline and adenosine in chronically hypoxic than control lungs suggested a higher normoxic vascular tone. This higher tone was not the sole cause of increased resistance in chronically hypoxic lungs, since maximal vasodilatation did not reduce resistance to control levels. The chief cause was probably encroachment of new muscle on the vascular lumen of small vessels.

4. Pulmonary arterial compliance was reduced in chronically hypoxic lungs.

5. Reactivity of vessels to ventilation hypoxia, over a wide range of oxygen tension, to angiotensin II (ANG II) and to adenosine 5′-triphosphate (ATP) was significantly greater in chronically hypoxic than control lungs, but thresholds to these stimuli were not reduced.
Novel Double-Isotope Technique for Enzymatic Assay of Catecholamines, Permitting High Precision, Sensitivity and Plasma Sample Capacity
Authors: Brown M. J. , Jenner D. A.
Published: August 2015

1. A novel use of a double-isotope method is described which allows radioenzymatic assays to combine precision and sensitivity.

2. In the catechol O-methyltransferase assay separate portions of each plasma sample are incubated with either S-[3H]- or S-[14C]-adenosyl-l-methionine. Standards of noradrenaline and adrenaline are added to the latter portions and are thus converted into standards of [14C]metadrenalines. These are added to the 3H-labelled portions after the incubation, where they function as tracers.

3. The final recovery of 14C radioactivity corrects for (a) the efficiency of methylation in the plasma sample concerned and (b) the recovery of metadrenalines during the extraction procedures.

4. The 3H/14C ratio is constant in each assay for a given catecholamine concentration and is determined for samples to which standards of noradrenaline and adrenaline are added to the 3H- (as well as the I4C-) labelled portions before the initial incubation.

5. The sensitivity of the assay is increased by using high specific radioactivity S-[3H]adenosyl-l-methionine (60-85 Ci/mmol), and low backgrounds are maintained by catecholamine depletion in vivo in the rats used for enzyme preparation.

6. Both catecholamines (1.5 pg/ml; 10 pmol/l) may be detected; the coefficients of variation are 3.0 and 3.2% for noradrenaline and adrenaline respectively (intra-assay) and 4.6 and 5.0% (inter-assay).