bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of the Acute Haemodynamic Effects of Propranolol and Pindolol at Rest and during Supine Exercise in Man
Authors: Svendsen T. L. , Carlsen J. E. , Hartling O. , McNair A. , Trap-Jensen J.
Published: August 2015

1. Dose-response curves for heart rate, cardiac output, arterial blood pressure and pulmonary artery pressure were obtained in 16 male patients after intravenous administration of three increasing doses of pindolol, propranolol or placebo. All patients had an uncomplicated acute myocardial infarction 6–8 months earlier.

2. The dose-response curves were obtained at rest and during repeated bouts of supine bicycle exercise. The cumulative dose amounted to 0.024 mg/kg body weight for pindolol and to 0.192 mg/kg body weight for propranolol.

3. At rest propranolol significantly reduced heart rate and cardiac output by 12% and 15% respectively. Arterial mean blood pressure was reduced by 9.2 mmHg. Mean pulmonary artery pressure increased significantly by 2 mmHg. Statistically significant changes in these variables were not seen after pindolol or placebo.

4. During exercise pindolol and propranolol both reduced cardiac output, heart rate and arterial blood pressure to the same extent. After propranolol mean pulmonary artery pressure was increased significantly by 3.6 mmHg. Pindolol and placebo did not change pulmonary artery pressure significantly.

5. The study suggests that pindolol may offer haemodynamic advantages over β-receptor-blocking agents without intrinsic sympathomimetic activity during low activity of the sympathetic nervous system, and may be preferable in situations where the β-receptor-blocking effect is required only during physical or psychic stress.
The Sympathetic Nervous System and the Renin-Angiotensin System in Borderline Hypertension
Authors: Henquet J. W. , Kho T. , Schols M. , Thijssen H. , Rahn K. H.
Published: August 2015

1. Plasma catecholamine levels as well as plasma renin activity and plasma renin concentration were compared in normotensive volunteers and in subjects with borderline hypertension. All subjects were studied at rest and during bicycle ergometry.

2. The two groups of volunteer subjects did not differ in the plasma concentrations of noradrenaline and adrenaline, both at rest and during physical activity. The same was true for plasma renin activity and plasma renin concentration. Furthermore, urinary excretion of noradrenaline, adrenaline and 4-hydroxy-3-methoxymandelic acid was similar in both groups.

3. The results do not support the assumption that there is increased sympathetic activity in subjects with borderline hypertension.
Role of Sensory Nerves in the Cardiovascular and Respiratory Changes with Isometric Forearm Exercise in Man
Authors: Duncan G. , Johnson R. H. , Lambie D. G.
Published: August 2015

1. To investigate the stimulus to the cardiovascular and respiratory systems during isometric exercise, two patients with sensory neuropathies affecting forearm afferent nerves were studied and their circulatory and respiratory responses compared with those of normal subjects. The contribution of pain to the cardiorespiratory changes was also investigated in normal subjects by using hypnosis to relieve pain during and after isometric exercise.

2. The patients and normal subjects performed fatiguing isometric forearm exercises on a handgrip dynamometer on at least two occasions, once with normal forearm circulation and once with the forearm circulation occluded by an arterial cuff during and after exercise. Blood pressure, heart rate, minute ventilation, oxygen consumption and ventilatory equivalent were measured before, during and after exercise.

3. During exercises with and without occlusion increases in blood pressure and heart rate in patients and in subjects under hypnosis were similar to those in control subjects. Changes in oxygen consumption were also similar to those of controls, but the patients showed a smaller rise in ventilation and no increase in ventilatory equivalent.

4. After exercise in normal subjects occlusion of the forearm circulation produced continued elevation of blood pressure and respiration. Blood pressure also remained elevated after exercise with occlusion in subjects under hypnosis, but not in patients with sensory loss. Respiration did not remain elevated in either subjects under hypnosis or patients.

5. The results suggest that cardiovascular and respiratory changes during isometric exercise can occur without involvement of muscle sensory nerves and that pain contributes substantially to the increase in respiration. Normal sensory innervation is apparently necessary only for maintenance of raised blood pressure after exercise with occlusion.
Purification and Characterization of Kallikrein from Plasma of Patients with Acute Pancreatitis
Authors: Toki Naotika , Sumi Hiroyuki , Takasugi Sumiyoshi
Published: August 2015

1. A kallikrein-like enzyme in plasma of patients with acute pancreatitis was further purified by successive hydroxyapatite/cellulose and Sepharose-4B column chromatography.

2. By these procedures 0.26 mg of purified enzyme with a specific activity of 215 S-2266 chromozyme units/mg of protein was obtained from 10 ml of original plasma.

3. The purified material was homogeneous as ascertained by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and had an apparent molecular weight of 31 000 as measured by gel filtration on Sephadex G-200.

4. It was confirmed immunologically that this enzyme was pancreatic kallikrein, which is distinct from plasma kallikrein, and that it could combine with α2-macroglobulin only in the presence of trypsin.
Total Body Potassium in Relation to Thyroid Hormones and Hyperthyroidism
Authors: Edmonds C. J. , Smith T.
Published: August 2015

1. Body weight and total body potassium were measured in 23 hyperthyroid patients before and at various stages during treatment and in 19 athyreotic patients who were being treated with high-dose l-thyroxine.

2. In the hyperthyroid patients the total body potassium rose by 23 ± 2.8% (sem) within a few weeks of restoring the blood thyroid hormone levels to normal. The body potassium values after treatment were close to that expected in these individuals if they were healthy indicating that a considerable loss of body potassium is usual in hyperthyroidism.

3. The gain of total body potassium in hyperthyroidism averaged 71 ± 8 mmol for each kg of body weight gained (compared with muscle potassium concentration of about 92 mmol/kg). In contrast, weight loss produced by dietary treatment of obesity caused very little change of body potassium (maximum averaged was 14 ± 4 mmol/kg wt. loss).

4. Among the patients with hyperthyroidism, the greatest muscular weakness was present in those with the greatest body potassium loss and these patients regained a large amount of potassium relative to weight on recovery.

5. Total body potassium changes were closely related to total plasma tri-iodothyronine concentrations but unrelated to the thyroxine levels.
Effects of Rest, Exercise and Warming on Serum Creatine Kinase Levels in Primary Hypothyroidism
Authors: O'Malley B. P. , Davies T. J. , Rosenthal F. D.
Published: August 2015

1. Serum creatine kinase and oral temperature were measured in 20 patients with primary hypothyroidism before and after 48 h bed rest. Fifteen of these patients were heated during the 48 h period. The remaining five acted as control subjects. In addition, creatine kinase and oral temperature were measured in five control subjects after a 30 min period of exercise and again after a 30 min period of resting.

2. The oral temperature rose and the serum creatine kinase levels fell only in those patients who were actively warmed. In the control subjects the period of exercise followed by resting caused no significant change in creatine kinase levels.

3. A subnormal body temperature appears to be an important determinant of the raised serum creatine kinase levels seen in patients with primary hypothyroidism.
Normal Urinary Protein Composition in the Female Wistar Rat and its Relationship to the Proteinuria Induced by Intraperitoneal Bovine Albumin
Authors: Lawrence Gillian M. , Brewer D. B.
Published: August 2015

1. Normal female Wistar rats showed a wide range of baseline protein excretion and albuminuria and could be divided into two distinct groups: (a) low-to-intermediate excretors, where daily baseline albumin excretion was below 1.8 mg/24 h and (b) high excretors, where daily baseline albumin excretion was 1.8–22 mg/24 h.

2. In low-to-intermediate excretors ‘sex-associated’ urinary specific proteins, supposedly present only in male rat urine, were excreted in larger quantities than albumin which constituted only 10–15% of the total urinary protein.

3. In high excretors up to 50% of the urinary protein was albumin and other serum proteins were also present in relatively larger quantities than the urinary specific proteins.

4. Baseline albumin excretion appeared to be a good indicator of the inherent efficiency of the glomerular filter and this was reflected in the response to intraperitoneal injection of heterologous serum albumin since, during periods where no significant glomerular epithelial cell foot-process loss had been incurred, the levels of proteinuria induced correlated well with baseline albuminuria.
Intestinal Glucose Transport in Acute Viral Enteritis in Piglets
Authors: Telch J. , Shepherd R. W. , Butler D. G. , Perdue M. , Hamilton J. R. , Gall D. G.
Published: August 2015

1. We studied intestinal glucose transport in pigs during the acute and convalescent phases of an invasive viral enteritis, transmissible gastroenteritis.

2. When diarrhoea was severe 40 h after experimental infection, net absorption of glucose, Na+ and water, measured by marker perfusion in the jejunum, was reduced; the enhancement of Na+ and water absorption in response to increasing perfusate glucose concentrations up to 120 mmol/l was diminished compared with the response observed in control and convalescent pigs.

3. Measured in vitro, 40 h after infection, unidirectional fluxes of 3-O-methyl-d-glucose across the jejunal epithelium were reduced and net absorption of the sugar was obliterated. Phlorizin (0.05 mmol/l), which completely inhibited net 3-O-methyl-d-glucose absorption in control tissue, had no significant effect on transmissible gastroenteritis jejunum.

4. Our data suggest that in this invasive viral enteritis, which closely resembles human rotavirus enteritis, glucose absorption is impaired as a result of defects in both active and passive glucose flux.

5. Differences between the mechanisms of viral diarrhoea, demonstrated by our study and those of the enterotoxigenic diarrhoeas, should be taken into consideration in formulating active therapeutic measures for children with acute viral diarrhoea.
Leucocyte ATP and Renal Failure
Authors: Mansell M. A. , Grimes A. J. , Jones N. F.
Published: August 2015

1. We have measured adenosine 5′-triphosphate (ATP) levels in isolated leucocyte suspensions from patients with renal failure.

2. Leucocyte ATP is reduced in these patients, unlike erythrocyte ATP which is known to be elevated in uraemia.

3. The relevance of reduced leucocyte ATP to the abnormalities of cation transport and cell function which occur in uraemia is discussed.
Impaired Response of Plasma Renin Activity to Tilting after Renal Transplantation
Authors: Cunningham J. , Vandenburg M. J. , Holly J. M. P. , Goodwin F. J.
Published: August 2015

1. Changes in plasma renin activity, plasma noradrenaline, pulse rate and blood pressure after tilting were measured in normal subjects and in patients with renal transplants.

2. There was a marked difference between the renin responses in the two groups, the increases in plasma renin activity in the control subjects being much greater than those in the transplanted patients.

3. Activation of the sympathetic nervous system after tilting, as indicated by changes in pulse rate, blood pressure and plasma noradrenaline, was similar in the two groups.

4. We conclude that the ability of the transplanted kidney to increase plasma renin activity after tilting is impaired, probably as a result of sympathetic denervation of the kidney during transplantation. The results suggest a dominant role of the sympathetic nervous system in the mediation of renin release after tilting.
Effect of Propranolol Therapy on Aldosterone Responses to Angiotensin II and Adrenocorticotropic Hormone in Essential Hypertension
Authors: Golub M. S. , Tuck M. L. , Fittingoff D. B.
Published: August 2015

1. The plasma aldosterone responses to exogenous angiotensin II and adrenocorticotropic hormone (ACTH) were studied before and after 1 month of propranolol therapy (120–240 mg/day) in eight patients with essential hypertension.

2. Basal supine plasma renin activity was decreased (P < 0.001) after propranolol, whereas plasma aldosterone was unchanged. After 3 h of upright posture the increases in both plasma renin activity and aldosterone were decreased (P < 0.05) after propranolol.

3. Plasma aldosterone responses to exogenous angiotensin II and ACTH were not significantly different after propranolol. Serum and urinary electrolytes and plasma cortisol were also unaffected by propranolol therapy.

4. It is concluded that changes in adrenal sensitivity are not responsible for maintaining unchanged supine plasma aldosterone concentrations after β-adrenoceptor antagonism in essential hypertension.
Ki+-Na+o Countertransport in Erythrocytes of Patients with Essential Hypertension
Authors: Adragna N. , Canessa M. , Bize I. , Solomon H. , Tosteson D. C.
Published: August 2015

1. We describe in this paper a new ouabain-insensitive pathway for Na+ and K+ in human erythrocytes. K+ efflux was measured in cells loaded by the p-chloromercuribenzene-sulphonate (PCMBS) procedure to contain approximately equal amounts of Na+ and K+. K+ efflux was stimulated by external Na+ in the presence of ouabain and frusemide. Na+-stimulated K+ efflux was 0.35 ± 0.12 (mmol h−1 l−1 of cells) in eight normal subjects and 0.64 ± 0.13 in 13 patients with essential hypertension.

2. The Na+-stimulated K+ efflux was not observed in cells loaded in the presence of EGTA. This inhibition by EGTA suggests that K+ efflux is dependent on intracellular calcium. The Ki+-Nao+ countertransport of hypertensive patients was also inhibited by EGTA. The elevated K+—Na+ countertransport of hypertensive patients could be due to a higher intracellular Ca2+ content (Cai2+) or to an increased affinity for Cai2+. The relationship of this pathway to the Gardos effect is not clear since Na+-stimulated K+ efflux occurs without metabolic depletion or inhibition of the Ca2+ pump. As a tentative hypothesis, we relate the Ca2+-dependent downhill movement of K+ and Na+ to the Ca2+-dependent channels described in muscle and nerve, but other hypotheses cannot be excluded at this stage of our research.
Increased Erythrocyte Lithium-Sodium Countertransport in Essential Hypertension: Its Relationship to Family History of Hypertension
Authors: Canali M. , Borghi L. , Sani E. , Curti A. , Montanari A. , Novarini A. , Borghetti A.
Published: August 2015

1. Erythrocyte lithium—sodium counter-transport was measured in 46 normotensive healthy controls without family history of hypertension, 15 subjects with essential hypertension, but without evidence of family history of high blood pressure, and 43 subjects with essential hypertension and at least one hypertensive first-degree relative.

2. Mean values (mmol h−1 l−1 of erythrocytes) were 0.248 ± 0.092 in controls, 0.258 ± 0.087 in hypertensive subjects without family history (not significant vs controls), 0.360 ± 0.115 in hypertensive subjects with family history of hypertension (P < 0.001 vs controls), 0.334 ± 0.117 in all hypertensive subjects, both with and without family history (P < 0.001 vs controls).

3. Our data confirm the finding of an increased erythrocyte lithium-sodium counter-transport, but with a significant overlap between essential hypertension and control values. Lithium-sodium countertransport is higher only in hypertensive subjects with at least one hypertensive first-degree relative.

4. We suggest that the increase of lithium-sodium countertransport in erythrocytes is not a consistent marker of essential hypertension. It seems to be associated with the family prevalence and/or the hereditability of hypertension, rather than with high blood pressure per se.
Changes in Plasma Renin Activity after Hypoglycaemia in Sympathectomized Man
Authors: Frier B. M. , Corrall R. J. M. , Pritchard J. L. , Sever P. S.
Published: August 2015

1. The changes in blood glucose, plasma noradrenaline and plasma renin activity were measured in 11 normal subjects and in six tetraplegic subjects with a transection of the cervical spinal cord (preganglionic sympathectomy), in response to acute insulin-induced hypoglycaemia (0.15 unit/kg).

2. After hypoglycaemia, a pronounced rise in plasma noradrenaline was observed in the normal subjects but was absent in the tetraplegic group; plasma renin activity increased markedly in both groups.

3. It is concluded that the stimulation of renin release in response to hypoglycaemia can occur independently of any activation of the sympatho-adrenal system.
Intralymphocytic Sodium Concentration as An Index of Response to Stress and Exercise in Young Subjects with Borderline Hypertension
Authors: Ambrosioni E. , Costa F. V. , Montebugnoli L. , Borghi C. , Magnani B.
Published: August 2015

1. A highly significant correlation between intralymphocytic sodium concentration and basal diastolic blood pressure can be found only in patients with sustained essential hypertension.

2. In subjects with borderline hypertension and in normotensive subjects with familial hypertension a highly significant correlation can be found between intralymphocytic sodium concentration and the increase in diastolic blood pressure induced by mental arithmetic or handgrip exercise.

3. The increase in diastolic blood pressure recorded during mental arithmetic and handgrip in patients with borderline hypertension and in genetic normotensive subjects is significantly greater if intralymphocytic sodium concentration is greater than 26 mmol/kg.
Effect of Extracellular Potassium on the Transport of Sodium and Potassium in Rat Thymocytes
Authors: Jones R. B. , Patrick J. , Hilton P. J.
Published: August 2015

1. The effect of extracellular potassium on the transport of sodium and potassium in rat thymocytes has been studied in vitro.

2. A significant increase in the rate constant for total and ouabain-sensitive sodium efflux was demonstrated at an extracellular potassium concentration of 1 mmol/l as compared with that at either 0 or 2 mmol/l.

3. At potassium concentrations below 3 mmol/l ouabain-sensitive sodium influx was observed suggesting sodium-sodium exchange catalysed by the sodium pump.

4. Both total and ouabain-insensitive potassium efflux rose with external potassium. A small ouabain-sensitive potassium efflux was observed at all levels of external potassium studied.

5. Total and ouabain-insensitive potassium influx increased with external potassium, but did not appear to saturate. Ouabain-sensitive potassium influx reached a maximum at an external potassium concentration of 2 mmol/l then decreased with increasing external potassium.
3-Methylbutanal Metabolism in the Adult Rat
Authors: Kubow S. , Anderson G. H. , Blendis L. M. , Goldberg E.
Published: August 2015

1. 3-Methylbutanal is a normal constituent of human plasma and is elevated in patients with hepatic encephalopathy. Therefore these studies examined the possible source and site of synthesis of 3-methylbutanal and its effect on the central nervous system of adult rats.

2. 3-Methylbutanal was found to be a normal constituent of rat plasma and increased two to five times when leucine comprised 5% of the diet. Neomycin in the diet prevented the leucine-induced rise in plasma 3-methylbutanal. When this was injected at a dose of 120 mg/kg abnormal EEG patterns and sleep-like behaviour occurred, whereas smaller amounts (30 mg/kg) increased brain serotonin concentrations.

3. 3-Methylbutanal is a normal component of rat plasma: it may be derived in part from colonic bacterial breakdown of leucine and may influence central nervous system function. A possible relationship of 3-methylbutanal to the pathogenesis of hepatic encephalopathy is suggested.
Plasma Levels of Vitamin D Metabolites in Diphosphonatetreated Rats
Authors: Trechsel U. , Taylor C. M. , Eisman J. A. , Bonjour J.-P. , Fleisch H.
Published: August 2015

1. Protein-binding assays have been used to measure plasma 1,25-dihydroxy-vitamin D [1,25-(OH)2D] as well as 25-hydroxy-vitamin D [25-(OH)D] in rats given 10 mg of phosphorus (P) day−1 kg−1 as ethane-1-hydroxy-1,1-diphosphonate (EHDP).

2. In control animals given a normal laboratory chow plasma 25-(OH)D and 1,25-(OH)2D were about 40 nmol/l and 300 pmol/l respectively.

3. EHDP produced a decrease of plasma 1,25-(OH)2D to below 50 pmol/l in 2 days.

4. Both in control and in EHDP-treated rats plasma 1,25-(OH)2D increased when dietary calcium (Ca) was restricted to 0.1%, or dietary P to 0.2%, indicating that the well-known stimulatory effect of Ca or P deprivation was at least partially effective in EHDP-treated rats.

5. In response to an increase of the oral supply of vitamin D3 to 65 nmol/day the plasma level of 25-(OH)D rose in both control and EHDP groups. Plasma 1,25-(OH)2D was not increased above the normal value in control rats. In EHDP-treated rats, however, plasma 1,25-(OH)2D rose to a level equal to that in controls, suggesting that the effect of EHDP on plasma 1,25-(OH)2D can be overcome at high precursor concentration.
The Effect of Indomethacin on Vasopressin-Induced Antidiuresis in Man
Authors: Padfield P. L. , Grekin R. J.
Published: August 2015

1. The effect of 3 days' treatment with indomethacin on the renal response to infused vasopressin was assessed in eight healthy volunteer subjects.

2. Indomethacin produced significant weight gain and an increase in serum potassium without a change in creatinine clearance.

3. Although indomethacin reduced maximum free water clearance in five subjects, the antidiuresis produced by an incremental infusion of physiological amounts of vasopressin was no different whether indomethacin had been taken or not.

4. Indomethacin, in the dose we have used, is known to reduce prostaglandin production and we therefore conclude that endogenous prostaglandins do not inhibit the effect of physiological amounts of vasopressin on water clearance, which makes it unlikely that prostaglandins are important in the day-to-day modulation of the response to vasopressin.
Comparison of Intrarenal and Extrarenal Converting-Enzyme Inhibition by SQ 20 881 on Canine Renal Blood Flow
Authors: Wong P. C. , Zimmerman B. G.
Published: August 2015

1. Successive infusions of SQ 20 881 given intra-arterially (i.a.) to the kidney at 0.4 and 0.8 μg min−1 kg−1 for 50 min each did not alter renal blood flow and renal vascular resistance in spite of 40–47% blockade of the angiotensin I (ANG I i.a.)-induced vasoconstrictor response.

2. SQ 20 881 administered intravenously (i.v., 0.5 mg/kg) after the higher intra-arterial dose did not further decrease the renal response to ANG I (i.a.), but caused an increase in renal blood flow and a decrease in renal vascular resistance.

3. These results indicate that SQ 20 881 has limited efficacy in blocking the renal response to ANG I (i.a.). Under the conditions of these experiments, the renal vasodilator response to SQ 20 881 appears to be due to inhibition of extrarenal rather than intrarenal converting enzyme.
On the Mechanism of Plasma Cholesterol Reduction in the Rat Given Probucol
Authors: Balasubramaniam S. , Beins D. M. , Simons L. A.
Published: August 2015

1. The effects of the cholesterol-lowering drug probucol on lipoprotein metabolism and on the key enzymes that regulate hepatic cholesterol metabolism in the rat were studied.

2. Probucol given for 2 weeks was accompanied by a significant reduction in plasma concentrations of low-density and high-density lipoproteins (LDL, HDL). The fractional catabolic rates of the apolipoproteins of HDL and LDL (apoHDL, apoLDL) were not affected by probucol, although the absolute rates of catabolism of both the apolipoproteins were significantly reduced.

3. The activities of 3-hydroxy-3-methyl-glutaryl-coenzyme A (CoA) reductase and cholesterol 7α-mono-oxygenase, as well as the rate of hepatic sterol synthesis, were unchanged during the first 2 weeks of probucol. More prolonged probucol led to inhibition of the activity of these enzymes and reduction in sterol synthesis, although the liver cellular content of cholesterol significantly increased.

4. It is postulated that a principal mode of action of the drug is to reduce the rate of lipoprotein synthesis.
Role of Prostaglandins in Bile Salt-Induced Changes in Rat Colonic Structure and Function
Authors: Rampton D. S. , Breuer N. F. , Vaja S. G. , Sladen G. E. , Dowling R. H.
Published: August 2015

1. The role of prostaglandins in mediating bile salt-induced diarrhoea was investigated with a colonic perfusion technique in vivo in rats either untreated or pretreated with the prostaglandin (PG) synthesis inhibitor, indomethacin.

2. Colonic perfusion with sodium deoxycholate (1 and 2 mmol/l) reduced net water and sodium absorption, whereas at a concentration of 5 mmol/l it caused net fluid secretion. Deoxycholate dose-dependently increased protein and deoxyribonucleic acid (DNA) output into the perfusion fluid and, at a concentration of 5 mmol/l, produced histological evidence of colonic mucosal damage (mucus release, goblet cell depletion, patchy epitheliolysis and inflammatory cell infiltration); histological change was less with deoxycholate at 2 mmol/l and did not occur at 1 mmol/l.

3. Output of immunoreactive prostaglandin E2 (PGE2) into the colonic perfusion fluid rose eight-, 10- and 270-fold after deoxycholate at 1, 2 and 5 mmol/l respectively.

4. Colonic perfusion with added PGE2, in concentrations 10 times lower (2.8 nmol/l) and 10 times higher (0.28 μmol/l) than those found in the perfusate after deoxycholate at 5 mmol/l did not alter mucosal function or structure. However, PGE2 in much higher concentration (0.28 mmol/l) reduced net absorption of water and sodium, increased protein output threefold and, as seen with light microscopy, produced excess surface mucus with minimal goblet cell depletion and no tissue damage.

5. Pretreatment with indomethacin reduced the colonic PGE2 output of rats perfused with deoxycholate at 2 and 5 mmol/l by 56 and 87% respectively, but the bile salt-induced changes in net water and sodium transport and DNA output were not significantly affected. The PG synthesis inhibitor reduced protein loss, goblet cell depletion and surface mucus seen after perfusion with deoxycholate at 2 mmol/l, although it did not prevent the more marked structural changes caused by deoxycholate at 5 mmol/l.

6. These results suggest that in rats prostaglandins (i) are not important mediators of the deoxycholate-induced impairment of colonic water and electrolyte transport, (ii) may contribute to the mucus secretion and goblet cell depletion produced by perfusion with deoxycholate in concentrations below those causing gross tissue damage, and that (iii) overt mucosal damage is not an essential prerequisite for prostaglandin release.
Calcium Antagonists Decrease Adrenal and Vascular Responsiveness to Angiotensin II in Normal Man
Authors: Millar J. A. , McLean Kathleen , Reid J. L.
Published: August 2015

1. The effect of the calcium antagonist nifedipine on the pressor and aldosterone responses to angiotensin II was studied in six normal subjects.

2. Blood pressure, pulse rate and plasma aldosterone, potassium and cortisol were measured during paired consecutive infusions of angiotensin II (5, 10 and 20 ng min−1 kg−1) on two separate occasions. Nifedipine (20 mg by mouth) was given, 30 min before the second set of infusions.

3. After nifedipine there were reciprocal changes in supine resting blood pressure (−7 mm Hg) and pulse rate (+18 min−1) and a significant decrease in the pressor response to angiotensin II (P < 0.05; Wilcoxon signed rank test).

4. Basal levels of aldosterone were not changed by nifedipine, but the response to angiotensin II was significantly attenuated (P < 0.05). Nifedipine had no effect on plasma potassium or cortisol.

5. Transmembrane movement of calcium is involved in the aldosterone response to angiotensin II in man. Calcium antagonists may lower blood pressure via decreased adrenal responsiveness to angiotensin II as well as by peripheral vasodilatation.
Sulphamidase Activity in Leucocytes, Cultured Skin Fibroblasts and Amniotic Cells: Diagnosis of the Sanfilippo a Syndrome with the Use of a Radiolabelled Disaccharide Substrate
Authors: Hopwood J. J. , Elliott Helen
Published: August 2015

1. Sulphamidase activity was assayed by incubation of the radiolabelled disaccharide O-(α-2-sulphamino-2-deoxy-d-glucopyranosyl)-(1 → 3)-l-[6-3H]idonic acid with homogenates of leucocytes and cultured skin fibroblasts and concentrates of urine derived from normal individuals, patients affected with sulphamidase deficiency disorder [mucopolysaccharidosis type IIIA (MPS IIIA): the Sanfilippo A syndrome], parents of such patients and patients affected with other mucopolysaccharidoses and lysosomal enzyme deficiencies.

2. the assay clearly distinguished affected homozygotes from normal controls, heterozygotes and other mucopolysaccharidoses types.

3. Sulphamidase displayed remarkable thermal stability; reaction rates were constant for at least 24 h at 60°C for leucocyte and 20 h at 37°C for cultured fibroblast preparations. Apparent Km values for fibroblast sulphamidase were 71 μmol/l at 37°C and 100 μmol/l at 50°C; the corresponding Vmax. values were 21 and 71 pmol min−1 mg−1 of protein respectively. an incubation temperature of 60h°C was used for the routine assay of sulphamidase activity in leucocytes, urine and amniotic supernatant preparations. the specific activities of fibroblast and amniotic cell sulphamidase, assessed at incubation temperatures of 37°C, were more than 10-fold the leucocyte enzyme activity at 60°C.

4. We recommend the use of radiolabelled disaccharide substrate for the assay of sulphamidase in leucocytes, skin fibroblasts and urine, for the routine enzymic detection of the sulphamidase deficiency disorder of the Sanfilippo A syndrome.
Creatinine Excretion as An Index of Myofibrillar Protein Mass in Dystrophic Mice
Authors: Murray C. E. , Warnes D. M. , Ballard F. J. , Tomas F. M.
Published: August 2015

1. Daily creatinine excretion in the urine of normal and dystrophic mice was determined and then the carcass proteins were quantitatively extracted into soluble, myofibrillar and collagenous fractions.

2. on a live body-weight basis, total carcass protein was 15% lower in dystrophic than in normal mice. Relative to carcass weight, however, the amount of protein was significantly lower only in male dystrophic mice.

3. the myofibrillar protein fraction comprised 36.3 and 32.5% of the total protein in male and female dystrophic mice and 48.8 and 45.0% respectively in normal mice. the decrease in myofibrillar protein in dystrophic mice was accompanied by an increase in the residual collagenous fraction of proteins.

4. the rate of excretion of creatinine was strongly correlated (r = +0.98) with the myofibrillar protein mass in each mouse. This relationship was the same for both normal and dystrophic mice, each gram of myofibrillar protein being associated with 3.6 μmol of creatinine excreted/day.

5. the creatinine excretion rate is a valid index of contractile muscle mass in murine dystrophy.
Time-Course of Vascular Resistance Changes in Mineralocorticoid Hypertension of Man
Authors: Wenting G. J. , Man in 'T Veld A. J. , Schalekamp M. A. D. H.
Published: August 2015

1. Repeated measurements of blood pressure, cardiac output (99mTc-labelled albumin dilution with single-probe precordial counting of radioactivity), plasma volume and extracellular volume were made in 20 subjects exposed to mineralocorticoid excess. Patients with aldosterone-producing adenoma (n = 14) were followed for 6 weeks during the recurrence of hypertension after spironolactone treatment had been stopped. Patients with adrenal insufficiency (n = 4) were followed for 6–9 weeks after treatment with dexamethasone (1 mg daily) and fludrocortisone (0.5 mg daily) was begun. Patients with severe orthostatic hypotension due to autonomic insufficiency (n = 2) were followed for 21 and 120 weeks while treated with fludrocortisone (0.25 mg daily). Measurements were made weekly during the first 6 weeks and with longer intervals thereafter.

2. All subjects showed increments of cardiac output, stroke volume, plasma volume and extracellular volume during the first 2 weeks with little or no increase in total peripheral resistance. Mean blood pressure rose from 104 ± 3 to 126 ± 5 mmHg (mean ± sem) (P < 0.001, n = 14) in that period in primary aldosteronism and from 85 ± 4 to 94 ± 6 mmHg (P > 0.05, n = 6) with fludrocortisone.

3. After 6 weeks hypertension was maintained by increased resistance in nine subjects, whereas cardiac output and plasma volume had returned towards normal (mean blood pressure at the end of the study 127 ± 4 mmHg). In the remainder hypertension was maintained by increased cardiac output and expanded plasma Volume for at least 6 weeks (mean blood pressure at the end of the study 131 ± 8 mmHg). The patients with the high-resistance pattern were older (56 ± 2 years) than the patients with the high-flow pattern (34 ± 2 years) (P < 0.01).

4. Mean blood pressure and extracellular fluid volume were positively correlated (r = 0.63, P < 0.001, n = 161). Cardiac output was positively correlated with plasma volume (r = 0.51, P < 0.001, n = 161), and total peripheral resistance was inversely correlated with the plasma volume/interstitial fluid volume ratio (r = 0.47, P < 0.001, n = 161).

5. The long duration of a high-flow state and the interindividual differences in progression of high-resistance hypertension argue against a cause-and-effect relation between flow and resistance through local metabolic factors (auto-regulation) as a hypertensive mechanism in sodium loading. The results are compatible with the view that fluid-shifts between the intravascular and extravascular compartments can influence the changes in cardiac output and resistance in early and sustained hypertension due to sodium overload. Cardiac output is increased when the proportion of fluid that is retained in the intravascular compartment is relatively high, and vascular resistance is increased when that proportion is relatively low.
Reflex Control of Sympathetic Nerve Activity and Heart Rate from Arterial Baroreceptors in Conscious Spontaneously Hypertensive Rats
Authors: Ricksten S. E. , Thorén P.
Published: August 2015

1. Mean arterial pressure (MAP), heart rate (HR) and splanchnic sympathetic nerve activity were recorded in conscious, 4 months old, male spontaneously hypertensive rats (SHR; n = 9) and matched normotensive Wistar—Kyoto (WKY) rats (n = 8).

2. The reflex bradycardia and reflex inhibition of splanchnic sympathetic nerve activity were studied in each animal during baroreceptor activation. MAP was raised 30–50 mmHg above control with slow, intra-arterial infusion of noradrenaline (1 μg min−1 kg−1 body wt.). There was a significant negative linear correlation between MAP and splanchnic nerve activity and between MAP and HR in all experiments during noradrenaline infusion.

3. The baroreceptor sensitivity with respect to heart rate control was greatly reduced in SHR compared with WKY rats, being 1.5 ± 0.1 beats min−1 mm−1 Hg and 3.7 ± 0.4 beats min−1 mm−1 Hg respectively (P < 0.001).

4. However, baroreceptor sensitivity with respect to control of splanchnic nerve activity, defined as percentage nerve inhibition per mmHg of MAP rise, did not differ statistically between the two groups: 1.8 ± 0.2%/mmHg for SHR and 2.0 ± 0.3%/mmHg for WKY rats.

5. It is suggested that the baroreceptor control of sympathetic ourflow is intact in conscious 4 months old SHR with early established hypertension.

6. It is also suggested that the impaired baroreceptor control of heart rate seen in SHR, and in human essential hypertension, is mainly due to an increased activity of the hypothalamic ‘defence area’, which can selectively block the efferent vagal component of the reflex bradycardia elicited from baroreceptor activation.
Regression of the Baroreceptor Resetting in Hypertension of Long Duration in Rats
Authors: Sumitani Marie , Krieger E. M.
Published: August 2015

1. The extent of reversal of baroreceptor resetting after pressure normalization was studied in rats with renal hypertension of up to 6 months duration. The aortas of these rats when compared with those of 2 month hypertensive rats were thicker (44%) and had a larger calibre (29%).

2. The more severe morphological alterations found in the 6 month hypertensive rats did not interfere with the reversibility of the resetting process. The entire range of pressure for baroreceptor activation showed a small downward displacement after 1 h and was functioning at a completely normal pressure 6 h after pressure normalization.

3. The data show that reversal of resetting from hypertension is a very rapid process that is independent of the duration of hypertension and the severity of morphological lesions. Moreover, they indicate that reversal is a permanent phenomenon because it was also observed after 2 days of pressure normalization.
Role of the Sympathetic Nervous System in Spontaneous Hypertension: Changes in Central Adrenoceptors and Plasma Catecholamine Levels
Authors: Palermo Anna , Costantini Carlo , Mara Gabriele , Libretti Arnaldo
Published: August 2015

1. There is evidence that dysfunction of central adrenergic neurons and the peripheral sympathetic nervous system are implicated in the development and maintenance of spontaneous hypertension.

2. Accordingly adrenoceptors of brain areas related to cardiovascular control (hypothalamus and lower brain stem) and plasma catecholamine levels were measured in male spontaneously hypertensive rats and in their normotensive Wistar-Kyoto controls at 11 weeks of age.

3. Assays of β, α1, and α2 receptor binding were performed by using respectively [3H]-dihydroalprenolol, [3H]clonidine and 3H-labelled WB4101 as ligand. Plasma catecholamines were assessed by high performance liquid chromatography with electrochemical detection.

4. No difference was observed on β-receptor binding sites in the two animal groups. On the other hand, α2 receptors were increased by 29% in the lower brain stem and α1 receptors showed an increase of 46% in the hypothalamus of the hypertensive rats. By Scatchard plot analysis, these changes were attributable to variations in the number rather than in the affinity of binding site.

5. Plasma noradrenaline levels were more elevated in the hypertensive rats, and no difference was observed in plasma adrenaline concentrations.

6. The increase in hypothalamic α1 receptors and the probably compensatory increase in lower brain stem α2 receptors suggest enhanced stimulation of the vasomotor centre. Hyperactivity of the peripheral sympathetic nervous system in spontaneous hypertension could therefore be secondary to a dysfunction of central adrenergic neurons projecting to the vasomotor centre of the brain stem.
Heterogeneity of Human Vascular Pre- and Post-Synaptic α-Adrenoceptors
Authors: Stevens M. J. , Rittinghausen R. E. , Moulds R. F. W.
Published: August 2015

1. The effects of various α-receptor agonists and antagonists on pre- and post-synaptic α-receptors of human isolated digital arteries and metacarpal (or metatarsal) veins have been studied.

2. The relative potency of phenylephrine compared with noradrenaline on the postsynaptic receptors was significantly greater in arteries than in veins.

3. The rank order of potency of various α-agonists on postsynaptic receptors was the same in arteries and veins except that in veins adrenaline was more potent than clonidine, whereas the reverse was the case in arteries.

4. Phentolamine showed no selectivity in either antagonizing postsynaptic responses or enhancing stimulation-induced transmitter release by antagonism at presynaptic α-receptors.

5. Yohimbine potently, but not selectively, antagonized postsynaptic responses to noradrenaline and phenylephrine in both arteries and veins, and enhanced stimulation-induced transmitter release to a greater extent in arteries than in veins.

6. Prazosin reduced the maximum response to noradrenaline (but not phenylephrine) to a significantly greater extent in veins than in arteries, and in veins alone shifted the phenylephrine curve to a greater degree than it did the noradrenaline curve. Prazosin did not significantly increase stimulation-induced transmitter release in either arteries or veins.

7. Phenoxybenzamine produced large increases in stimulation-induced tritium outflow which were significantly greater in arteries than in veins (even in the presence of cocaine).

8. It is concluded firstly that the postsynaptic α-adrenoceptors of these tissues are not a homogeneous population and that differing proportions of these receptors are present in the digital arteries and the metacarpal veins, and secondly that the sensitivities of the presynaptic α-adrenoceptors in the two tissues may also be different.
A Monoclonal Antibody for Immunopurification of Human Renin
Authors: Pau B. , Simon D. , Galen F. X. , Devaux C. , Soubrier F. , Ménard J. , Corvol P.
Published: August 2015

1. A mouse hybridoma secreting an antibody directed against human renin was obtained by fusion of spleen cells with NS 1 myeloma cells. This monoclonal antibody recognizes human and monkey renins but neither hog nor mouse renins nor the acid proteinase cathepsin D.

2. Monoclonal antibody was coupled to Sepharose 4 B. The immunoadsorbent thus obtained was very efficient in purifying both active and inactive human renin from renal or extrarenal sources.

3. Renin enrichment up to 3500-fold was obtained in a single step.
Immunological and Immunofluorescent Studies of Human Angiotensin-Converting Enzyme
Authors: Takada Yasuharu , Unno Masazumi , Hiwada Kunio , Kokubu Tatsuo
Published: August 2015

1. Human angiotensin-converting enzyme from kidney, lung, small intestine, plasma and urine was found to be immunologically indistinguishable by double immunodiffusion and inhibition of enzyme activity with specific anti-(human kidney enzyme) antibody.

2. Partial inhibition of the enzyme activities from hog, dog and rat sera by the antibody was found, but no inhibition was observed in the enzymes from sheep and bovine sera.

3. Human angiotensin-converting enzyme was located in two types of cells by an immunofluorescent technique using the purified antibody and fluorescein-labelled anti-(rabbit immunoglobulin) antibody. These were the vascular endothelial cells of alveolar capillaries and of pulmonary interstitial small vessels, and the epithelial cells of proximal tubules in the kidney and of mucous membrane in the small intestine.
Relationship between Plasma Renin and Cortisol in Hypertensive Patients
Authors: Atlas S. A. , Case D. B. , Sealey Jean E. , Laragh J. H.
Published: August 2015

1. Plasma cortisol at 08.00 hours was significantly higher (P < 0.005) in patients with high-renin essential or renovascular hypertension (22.6 ± 1.6 μg/100 ml) than in patients with normal-renin (15.4 ± 1.2) or low-renin (11.9 ± 1.2) forms of hypertension.

2. Plasma cortisol at 12.00 or 16.00 hours did not differ significantly among the three groups; thus the diurnal swing in plasma cortisol was steepest in patients with high plasma renin.

3. Among all patients studied, there was a direct relationship between 08.00 hours plasma cortisol and ambulatory plasma renin activity (r = 0.65, P < 0.001).

4. In patients with high-renin values, 08.00 hours plasma cortisol fell by 39 ± 6% after 10 days treatment with the converting enzyme inhibitor captopril. No consistent decreases were observed in the normal- or low-renin groups.

5. We conclude that the renin—angiotensin system may interact with the pituitary—adrenal axis to influence circulating levels of cortisol. This effect might conceivably contribute to the pathogenesis of certain high-renin states.
ACTH Stimulates Plasma Renin and Angiotensin II in Man
Authors: Oelkers W. , Köhler A. , Belkien L. , Fuchs-Hammoser R. , Maiga M. , Scherer B. , Weber P. C.
Published: August 2015

1. Adrenocorticotropic hormone (ACTH; 10 i.u./day) was infused for 34 h into normal male subjects. Some subjects were additionally treated with propranolol or indomethacin. Others received sham infusions or hydrocortisone infusions instead of ACTH.

2. ACTH, but not sham or hydrocortisone infusions, led to a significant increase in plasma renin activity and angiotensin II concentration with a lag period of 7–10 h and a maximum response after 24 h. ACTH may be a physiological regulator of renin secretion, perhaps through a ‘trophic’ effect on the juxtaglomerular apparatus.

3. The effect of ACTH on renin is not mediated by a rise in plasma renin substrate, probably not by renal β-adrenoreceptors, but perhaps by prostaglandins.

4. A dissociation between plasma cortisol and aldosterone during ACTH infusion suggests that ACTH, in this dosage, stimulates aldosterone on the second day through renin and angiotensin II, before its secretion is finally suppressed during more prolonged infusion.
Two Forms of Plasma Renin after Activation In Vitro and their Relation to Natural Plasma Renin
Authors: Derkx F. H. M. , Schalekamp M. P. A. , Schalekamp M. A. D. H.
Published: August 2015

1. Inactive renin in human plasma can be activated by pH 3.3-dialysis (generation of acid-activated renin), by clotting factor XII-mediated prekallikrein to kallikrein conversion after pH has been restored to neutral (generation of acid-kallikrein-activated renin) or by the addition of trypsin (generation of trypsin-activated renin).

2. Natural active renin, acid-kallikrein-activated renin and trypsin-activated renin behave similarly during affinity chromatography on Blue-Sepharose CL-6B and during gel filtration on Sephadex G-100. They also show similar reaction kinetics with similar pH-optimum curves when acting on sheep renin substrate.

3. Acid-activated renin is different. It is retained on Blue-Sepharose columns and it is inactivated at neutral pH during incubation at 37°C. This contrasts with the other forms of renin activated in vitro and with natural active renin. The pH-optimum curve of acid-activated renin, when acting on sheep renin substrate, is also different from that of the other forms of active renin.

4. It is to be proven that the renins generated in vitro by neutral serine proteinases are identical with natural active renin, but clearly they bear more resemblance to natural renin than acid- activated renin does. Our preliminary conclusion is that acid-activated renin is a ‘laboratory renin’, which does not circulate in normal peripheral venous plasma.