bluuebunny/crossref_metadata_2025 huggingface dataset:
Radioimmunoassay Measurement of Urinary Ligandin Excretion in Nephrotoxin-Treated Rats
Authors: Bass N. M. , Kirsch R. E. , Tuff S. A. , Campbell J. A. , Saunders J. S.
Published: August 2015

1. A radioimmunoassay was used to establish normal urine excretion of ligandin, a renal tubular protein, in rats, and to study the pattern of ligandin excretion after nephrotoxin administration.

2. Validation of radioimmunoassay measurement of ligandin in urine is described. A normal range of 2–46 ng/h was obtained for ligandin excretion in rats (n = 24).

3. Mercuric chloride (HgCl2; 10 mg/kg) administration resulted in a significant increase in ligandin excretion within 6 h, preceding the onset of significant azotaemia. Serum ligandin concentrations were raised after 12 h, while renal ligandin concentration fell to 30% of control values by 24 h.

4. Rats given HgCl2 (5 mg/kg) developed massive ligandinuria between 6 and 12 h, which declined to normal values by 72 h. Potassium dichromate (K2Cr2O7; 7 mg/kg) administration produced a comparatively moderate increase in ligandin excretion after 24 h.

5. The time course of ligandin excretion in HgCl2- and K2Cr2O7-treated rats correlated with the histological sequence of damage to the pars recta and pars convoluta of the proximal tubule respectively.

6. The results of this study confirm that renal ligandin is confined mainly to the pars recta of the proximal tubule, and small quantities of this protein are present in the pars convoluta. Radioimmunoassay provides a sensitive and specific means for measuring ligandin in urine and provides a valuable tool for the detection and study of renal tubular damage.
Effect of Aging on Free Amino Acids and Electrolytes in Leg Skeletal Muscle
Authors: Möller P. , Bergström J. , Eriksson S. , Fürst P. , Hellström K.
Published: August 2015

1. The concentrations of electrolytes and free amino acids in plasma and the quadriceps femoris muscle were studied in ten apparently healthy elderly men, 52–77 years of age. The results were compared with those previously recorded for men 20–36 years old.

2. The two groups of subjects did not differ with regard to serum electrolytes and intracellular water content but the extracellular water in the older subjects exceeded that of the younger group by about 50%. The muscle specimens of the elderly men were also characterized by a 40% elevation of their total contents of Na+ and Cl−, whereas the content of K+ and Mg2+ was almost identical in both groups.

3. The means recorded for the plasma concentrations of most amino acids tended to be higher in the elderly men. The differences reached statistical significance for tyrosine, histidine, valine, lysine and total essential amino acids. In keeping with the findings in plasma, the amino acid concentrations in the muscle of the older group tended to exceed those of the younger ones. The difference reached statistical significance with regard to total amino acids, essential and non-essential amino acids, aspartate, alanine, citrulline, histidine, arginine, leucine and lysine. The various mechanisms that may contribute to these findings are discussed.
Comparison of Two Rebreathing Methods for the Determination of Mixed Venous Partial Pressure of Carbon Dioxide during Exercise
Authors: Heigenhauser G. J. F. , Jones N. L.
Published: August 2015

1. Duplicate measurements were made of mixed venous Pco2 (Pv̄, co2) by two rebreathing methods during steady-state exercise at three power outputs in seven subjects. One method employed a high initial bag CO2 concentration to obtain equilibrium of CO2 in the lung—bag system before recirculation (equilibrium method); in the other, a low initial bag CO2 concentration was used and a statistical method was applied to alveolar Pco2 measurements before recirculation, to obtain the asymptote from the exponential rise in end-tidal Pco2 during rebreathing (exponential method).

2. The reproducibility was similar; sd of duplicate determinations of Pv̄, co2 was 0·15 kPa (1·1 mmHg) for the equilibrium method and 0·20 kPa (1·5 mmHg) for the exponential method. Measurements of Pv̄, co2 by the exponential method were systematically lower than the equilibrium method. When the equilibrium Pv̄, co2 was corrected for the alveolar—arterial (‘downstream’) Pco2 difference, using published values, Pv̄, co2 was similar for both methods.

3. As an alveolar to arterial Pco2 difference did not appear to exist with the exponential method, it is concluded that the previously described disequilibrium between alveolar and arterial Pco2 during rebreathing in exercise is mainly related to prevention of net CO2 movement from the pulmonary capillary blood in the equilibrium method, and is not present when continuous CO2 evolution occurs in the exponential method.
Cardiac Effects of Angiotensin Antagonists in Normotensive Rats
Authors: Sen S. , Tarazi R. C. , Bumpus F. M.
Published: August 2015

1. Angiotensin II (AII) antagonists, namely Sar1,Ile8-AII, Sar1,Ala8-AII and Sar1,Thr8-AII, were administered daily for 4 weeks to normotensive rats to study their effect on cardiac hypertrophy.

2. None of the antagonists altered blood pressure significantly but Sar1,Ile8-AII and Sar1,Ala8-AII produced a significant increase in heart weight, as compared with untreated age-matched control rats. Administration of Sar1,Thr8-AII did not produce cardiac hypertrophy.

3. A significant increase in catecholamine concentration was observed in the ventricles of rats treated with Sar1,Ile8-AII and Sar1,Ala8-AII but no change was found in the group treated with the Sar1,Thr8-AII analogue. The production of cardiac hypertrophy by Sar1,Ile8-AII was prevented by bilateral adrenalectomy, suggesting an important role for catecholamines in modulating cardiac hypertrophy.
Faecal Methylamine in Normal and Uraemic Subjects
Authors: Owens C. W. I. , Padovan W.
Published: August 2015

1. A ninhydrin-reacting substance seen during ion-exchange chromatography of faecal dialysate obtained in vivo from normal and uraemic subjects has been isolated and identified as methylamine.

2. Faecal dialysate concentrations of methylamine were higher in uraemic subjects and were related to the degree of renal impairment (P < 0·05).

3. Methylamine concentrations in faecal dialysate and centrifugate were not significantly different.
Analysis of 47Ca Kinetics in Normal Subjects by Means of a Compartmental Model with a Non-Exchangeable Plasma Calcium Fraction
Authors: Wajchenberg B. L. , Leme P. R. , Ferreira M. N. L. , Filho J. Modesto , Pieroni R. R. , Berman M.
Published: August 2015

1. 47Ca kinetic studies were performed in eight normal young adult males. Plasma, urinary and faecal stable and radioactive calcium and whole-body radioactivity were measured for up to 40 days after intravenous administration of the tracer.

2. The plasma radioactivity data could be fitted to the sum of four exponentials corresponding to a four-compartment model, but this model did not account for the consistently greater 47Ca specific radioactivities in plasma relative to those in urine at the same time in five of the subjects.

3. A non-exchangeable fraction of plasma calcium estimated as 5% of the mass in the plasma compartment was postulated to account for this finding.

4. An estimate of the insensible losses of calcium was obtained from the whole-body radioactivity counting data.
Intestinal Transport of a Tetrapeptide, l-Leucylglycylglycylglycine, in Rat Small Intestine in Vivo
Authors: Chung Y. C. , Silk D. B. A. , Kim Y. S.
Published: August 2015

1. The intestinal transport mechanism for the tetrapeptide l-leucylglycylglycylglycine, Leu-Gly-Gly-Gly, and its relation to the transport of free Leu, Leu-Gly and Leu-Gly-Gly were investigated in vivo by means of jejunal perfusion in rats.

2. The rates of net Leu absorption from peptides (Leu-Gly and Leu-Gly-Gly-Gly) were significantly greater than those from the free amino acid mixtures when the test solutions were perfused at a concentration of 15 mmol/l.

3. Net Leu absorption rates from Leu-Gly (10 μmol/ml) and Leu-Gly-Gly (10 μmol/ml) were extensively inhibited (84% and 68% respectively) by Gly-Pro at 100 mmol/l, whereas Gly-Pro had no effect on Leu absorption from Leu-Gly-Gly-Gly. l-Alanine (Ala, 100 μmol/ml), on the other hand, which completely inhibited Leu absorption during perfusion of free Leu, inhibited Leu uptake from Leu-Gly-Gly-Gly only about 50% at all concentrations studied. Ala had no effect on Leu absorption from Leu-Gly and Leu-Gly-Gly (10 μmol/ml).

4. Neither Ala at 100 μmol/ml nor Gly-Pro at 100 μmol/ml had any effect on brush-border aminopeptidase activity in vitro, suggesting that the hydrolytic capacity of the intestinal mucosal brush border was unaltered when Ala or Gly-Pro was included in the perfusion mixture. l-Alanyl-β-naphthylamide (20 μmol/ml), which inhibited brush-border aminopeptidase activity by 85% in vitro, failed to block substantially net Leu absorption from Leu-Gly and Leu-Gly-Gly-Gly.

5. The data presented suggest that, although some of the Leu from the tetrapeptide, Leu-Gly-Gly-Gly, may be hydrolysed before transport, nearly 50% of the tetrapeptide appears to be transported intact. Although Leu-Gly, Leu-Gly-Gly and Gly-Pro seem to share a common transport mechanism, the system used for intact Leu-Gly-Gly-Gly absorption seems to be distinct. However, the present study does not exclude the possibility that binding of the tetrapeptide to the brush-border aminopeptidase alters the affinity of Leu for the amino acid carrier, and therefore further studies are necessary before firm conclusions can be made on the general mechanism of tetrapeptide transport.
Evidence that the Acute Cardiovascular Response to Isoprenaline is Partly Mediated via Renin Release
Authors: Anderson G. H.
Published: August 2015

1. The possible effect of the increased plasma renin activity induced by β−adrenoreceptor stimulation in supporting arterial pressure has been studied in five normal subjects on a diet of 100 mmol of sodium/day for 4 days or 40 mmol of sodium/day for 4 days by infusing isoprenaline at 1·0, 2·0 or 3·0 μg min−170 kg−1, each for 1 h with 45 min between each infusion rate. During the last 30 min of each isoprenaline dose, the angiotensin II analogue [Sar1, Ala8]angiotensin II (saralasin) was infused.

2. Isoprenaline significantly (at least P <0·05) increased the pulse rate, systolic arterial pressure and plasma renin activity; the diastolic blood pressure decreased but the mean arterial pressure did not change. Saralasin administered to subjects on the 100 mmol of sodium/day diet significantly (at least P < 0·05) lowered mean arterial pressure at the two highest isoprenaline infusion rates.

3. With patients on a low sodium diet, saralasin lowered mean arterial pressure at all three isoprenaline infusion rates. On the low sodium diet the fall in mean arterial pressure caused by saralasin was significantly greater (P < 0·05) at the isoprenaline infusion rate of 3·0 μg min−1 70 kg−1 than at the infusion rate of 1·0 μg min−1 70 kg−1. The change in mean arterial pressure with saralasin before and during isoprenaline infusion on both diets was significantly correlated (r = −0·39, n = 38, P < 0·01) with the plasma renin activity measured immediately before saralasin infusion.

4. It is concluded that during β−adrenoreceptor stimulation the increased plasma renin activity (acting through angiotensin) supports arterial pressure.
Measurement of Water Distribution and Transcapillary Solute Flux in Dog Lung by External Radioactivity Counting
Authors: Prichard J. S. , Lee G. de J.
Published: August 2015

1. A method for measuring the pulmonary water compartments in vivo in anaesthetized dogs is described.

2. The technique depends upon the sequential intravenous injection of markers labelled with γ-ray-emitting isotopes. Each is allowed to become evenly distributed throughout the compartment to which it is confined. A calibrated γ-counter placed at the surface of the inflated lung then records a count rate related to the total quantity of isotope in unit volume of tissue. The size of each water compartment can be calculated from the external count rate and the isotopic concentration of the marker in plasma.

3. The markers used were 125I-labelled serum albumin for plasma, [125I]iodide for extracellular water and [125I]iodoantipyrine for total water.

4. The method was extended to calculate transcapillary flux rates of serum albumin and showed that rapid exchange of serum albumin takes place between the plasma and interstitial space.

5. Results obtained non-invasively by the isotopic method were compared with direct measurements. Agreement was good.
Effect of Chronic Clonidine Treatment and its Abrupt Cessation on Mean Blood Pressure of Rats with a Normal or An Elevated Blood Pressure
Authors: Atkinson J. , Boillat Nicole , Pera-Bally Roselyne , Peters-Haefeli Lise , Kirchertz E. J.
Published: August 2015

1. Clonidine (6 mg of base/1 of water) was given as drinking fluid to normotensive rats or rats with established or early hypertension.

2. Spontaneous hypertensive rats (6 months old: average dose of clonidine, 0·6 mg 24 h−1 kg−1) showed a sustained fall in blood pressure over 3 weeks.

3. The same clonidine solution given for 6 weeks to two-kidney Goldblatt rats with early-stage hypertension (average dose of clonidine: 1 mg 24 h−1 kg−1) or spontaneously hypertensive rats (clonidine dose: 1 mg) induced a fall in mean blood pressure, but no change in normotensive rats.

4. Replacement of clonidine by water induced hypertension and lability which led to death in hypertensive but not in normotensive rats.
Cardiovascular Design after ‘Reversal’ of Long-Standing Renal Hypertension in Rats
Authors: Lundgren Y. , Weiss Lilian
Published: August 2015

1. After 4–5 months of renal hypertension in rats renal artery ‘declipping’ was performed. Eight weeks afterwards paired hindquarter perfusions were performed on the declipped rats and normotensive control rats, exploring the relationships between mean arterial pressure and flow, from maximal vasodilatation to maximal vasoconstriction, induced by graded noradrenaline infusions. Left ventricular weights were measured.

2. Declipping caused a fall in mean arterial pressure from 180 to 135 mmHg, though still after 8 weeks the mean pressure was 19% higher than in normotensive control rats.

3. All parameters reflecting design and reactivity of the resistance vessels and left ventricular weight decreased significantly, but not as much as mean arterial pressure, and were still significantly increased compared with those of control rats.

4. Thus neither mean arterial pressure nor cardiovascular design was normalized 8 weeks after ‘reversal’ of long-standing renal hypertension, in contrast to short-standing renal hypertension where both are completely normalized 3 weeks after declipping.
Effect of Acid, Trypsin and Cold Treatment and of Renin— Plasma Interaction on the Activity of Renin Secreted by Rat Kidney
Authors: Nakane H. , Nakane Y. , Corvol P. , Menard J.
Published: August 2015

1. Renin release from the isolated perfused rat kidney was markedly stimulated by isoprenaline or anoxia. Renin secreted into the blood-free perfusate was not activated by exposure to cold or dialysis to pH 3·3, suggesting the absence either of cryo- or acid-activatable renin or of factors necessary to activate inactive renin.

2. Trypsin treatment did not change renin concentration in the perfusate samples.

3. When binephrectomized rat plasma was added to perfusate samples before dialysis, renin concentration in the acidified samples was significantly higher than in samples dialysed to pH 6·5. Diminished renin recovery in the latter samples caused this difference. Binephrectomized rat plasma itself had no significant renin activity before or after acid dialysis, indicating the absence of any important extrarenal source of active or acid-activatable renin in rats.

4. Acidification of binephrectomized rat plasma before its addition to the perfusate samples markedly reduced the difference between renin recovery during dialysis to pH 3·3 and dialysis to pH 6·5, indicating that acidification irreversibly inhibited renin inactivation by binephrectomized rat plasma. No net increase in renin concentration was observed in any of our experiments.

5. These results suggest that rat kidney does not secrete inactive renin. They also point to the existence of renin inactivation by rat plasma at neutral pH, which might lead to overestimation of acid-activatable renin in rats.
Constriction—Distension Relationships of Resistance Vessels in Normo- and Hyper-Tension
Authors: Folkow B.
Published: August 2015

A haemodynamic analysis of resistance vessel behaviour in normo- and hyper-tension has been performed, relating vessel design, degree of contraction, wall distensibility and transmural pressure to each other in a way which allows a semiquantitative prediction of their respective influences in various situations.
Choice of Control Groups in the Appraisal of Sympathetic Nervous Activity in Essential Hypertension
Authors: Jones D. H. , Hamilton Carlene A. , Reid J. L.
Published: August 2015

1. Plasma noradrenaline concentrations were similar in normotensive and hypertensive outpatients, but were significantly lower in laboratory control subjects.

2. Standing plasma noradrenaline concentrations were similar in all three groups.

3. Urinary vanillyl mandelic acid, catecholamines and metanephrines were also similar in the normotensive and hypertensive groups.

4. Laboratory controls, possibly because of familiarity with the techniques of sphygmomanometry and blood sampling, may attain a ‘basal’ resting level of sympathetic nervous discharge more readily and rapidly than subjects who are unfamiliar with such procedures.

5. After orthostatic stimulation by standing for 2 min, the activity of the sympathetic nervous system, as determined by pulse rate and plasma noradrenaline concentrations, was similar in the three groups, despite the lower starting values in the laboratory staff.

6. The absence of differences in plasma noradrenaline or urinary catecholamine and metabolite concentrations does not support the hypothesis of excessive sympathetic nervous activity in essential hypertension.
Effect of Propranolol on the Ventilatory Response to Hypercapnia in Man
Authors: Trembath P. W. , Taylor Elizabeth A. , Varley J. , Turner P.
Published: August 2015

1. The effect of a single oral dose of propranolol on the ventilatory response to hypercapnia has been studied in five healthy subjects.

2. Propranolol produced a small but significant reduction in the slope of the ventilation/end-tidal Pco2 regression line.

3. Propranolol did not significantly change vital capacity or forced expiratory volume in 1 s.
Effect of General Anaesthesia on Renal Haemodynamics in the Rat
Authors: Koeppen B. M. , Katz A. I. , Lindheimer M. D.
Published: August 2015

1. The effect of sodium pentobarbital and Inactin anaesthesia on renal haemodynamics in the rat was evaluated with radioactive microspheres 15 μm in diameter.

2. Both anaesthetic agents caused substantial decrements in total renal blood flow (sodium pentobarbital, −34%; Inactin, −24%) compared with unanaesthetized animals.

3. Measurements of renal function obtained in rats anaesthetized with either of these anaesthetic agents should be interpreted with caution.
Impairment of Flow in Routine Gravity-Fed Intravenous Infusions to Surgical Patients
Authors: Clarke E. W. , Jamison J. P. , Quartey-Papafio J. B.
Published: August 2015

1. Gravity-fed intravenous infusions were studied in patients by using continuous flow recording and a new resistance-measuring method.

2. A common, though preventable, cause of reduced flow was the gradual deformation of the plastic tubing under the regulator clamp.

3. In many cases there was some constriction of the cannulated vein and in a few this constriction was severe enough to seriously impair the infusion. The severity of the constriction varied periodically.

4. There was no evidence of trouble due to a generally raised pressure in the arm veins nor was clotting in the cannula a serious problem.

5. A simple test is described which may be found useful clinically for assessing the difficult infusion.
Vascular Reactivity in the Pathogenesis of Spontaneous Hypertension
Authors: Berecek Kathleen H. , Rascher W. , Gross F.
Published: August 2015

1. Alterations in vascular reactivity were assessed in isolated artificially perfused kidneys from stroke-prone spontaneously hypertensive (spSH) rats at different stages of hypertension and after neonatal sympathectomy with 6-hydroxydopamine (6-OHDA).

2. During the pre-hypertensive stage, and the early and chronic stages of hypertension, the responses to noradrenaline, vasopressin, serotonin and angiotensin II were enhanced in renal vascular beds from spSH animals compared with age- and sex-matched Wistar—Kyoto (WK) rats; dose—response curves were shifted to the left, had steeper slopes, greater maximal responses and decreased thresholds.

3. With increasing severity and duration of hypertension, renal vascular resistance at maximal vasodilatation increased, the slopes of the dose-response curves were steeper and maximal responses were greater.

4. Neonatal sympathectomy with 6-OHDA greatly attenuated but did not prevent the eventual development of hypertension; furthermore, this treatment had no effect on the enhanced resistance or reactivity in renal vascular beds from spSH rats.

5. The appearance of enhanced resistance and reactivity in the early stages of hypertension and the inability to prevent these vascular changes by neonatal sympathectomy suggest that these alterations are a primary pathogenic mechanism in spSH rats.
Activators of Inactive Renin (‘Prorenin’) in Human Plasma: Their Connection with Kinin Formation, Coagulation and Fibrinolysis
Authors: Derkx F. H. M. , Bouma B. N. , Tan-Tjiong H. L. , Schalekamp M. A. D. H.
Published: August 2015

1. Human plasma was treated at 4°C with acid, trypsin, plasmin, streptokinase, urokinase, active Hageman factor fragment (β-XIIa) and β-XIIa-activated plasma prekallikrein (Fletcher factor). The conversion of inactive into active renin (activation) was studied in normal plasma (n = 10), Hageman factor-deficient plasma (n = 2), Fletcher factor-deficient plasma (n = 1) and plasminogen-free plasma (n = 4).

2. In normal plasma inactive renin was activated at pH 7·5 after treatment at pH < 4·0; at pH 3·3 the results were the same as with trypsin. This was also the case in plasminogen-free plasma. In Hageman factor-deficient plasma and in Fletcher factor-deficient plasma, however, the quantities of renin that were activated after acidification were much smaller than with trypsin. The addition of physiological amounts of active kallikrein to pH 3·3-pretreated Hageman factor-deficient plasma caused complete activation of renin. In contrast, the addition of active Hageman factor fragment to pH 3·3-pretreated Fletcher factor-deficient plasma had little or no effect.

3. Plasmin, streptokinase-activated plasminogen and urokinase-activated plasminogen activated inactive renin in pH 4·0-pretreated normal plasma as well as in pH 4·0-pretreated Hageman factor-deficient plasma and Fletcher factor-deficient plasma.

4. It is concluded that inactive renin is activated by two separate proteolytic pathways: one pathway depends on both Hageman factor and plasma prekallikrein, and the other pathway depends on plasminogen. In the Hageman factor-dependent pathway plasma kallikrein and not Hageman factor is the major activator of inactive renin. It is assumed that pH 3·3-treatment of plasma destroys the major inhibitors of kallikrein and that pH 4·0-treatment destroys the major inhibitor of plasmin.
Plasmin Can Activate Plasma Prorenin but is Not Required for the Alkaline Phase of Acid Activation
Authors: Sealey Jean E. , Atlas S. A. , Laragh J. H. , Silverberg M. , Kaplan A.P.
Published: August 2015

1. Plasma prorenin is an inactive form of renin that is converted into active renin at alkaline pH in previously acidified plasma; this conversion of prorenin into renin is mediated by Hageman factor-dependent activation of prekallikrein, which, in turn, leads to prorenin activation.

2. Since plasma kallikrein can activate plasminogen, the present studies were designed to evaluate whether alkaline-phase activation of prorenin by plasma kallikrein is mediated via plasminogen activation.

3. We demonstrated that plasminogen is present in acid-treated plasma in sufficient quantity to convert prorenin into renin after activation by streptokinase.

4. However, alkaline-phase activation was completely normal in plasminogen-free plasma.

5. Therefore alkaline-phase activation of plasma prorenin is mediated by plasma kallikrein but is not dependent on kallikrein activation of plasminogen.
Release of Active and Inactive Renin by the Human Kidney
Authors: Aoi W. , Seto S. , Doi Y. , Murayama M. , Tasaki S. , Suzuki S. , Kuramochi M. , Hashiba K.
Published: August 2015

1. Active and inactive renin were assayed in plasma of the renal veins and the inferior vena cava below the kidney in eight patients with hypertension and unilateral renal abnormalities, 20 min after the patients had resumed the upright position.

2. The concentration of active renin on the affected side was significantly higher than that on the non-affected side. The concentration of inactive renin on the affected side was significantly lower than that on the non-affected side and in the inferior vena cava.

3. These findings suggest either that the affected kidney mainly secretes active renin, which is then converted into inactive renin in the extrarenal circulation, or that the affected kidney activates inactive renin.
Effect of Age on Angiotensin II Receptors from Rat Brain
Authors: Baxter Claire , Horvath J. , Duggin G. , Tiller D.
Published: August 2015

1. Angiotensin II receptor binding was studied in specific regions of rat brain at different ages from birth to 14 weeks.

2. The number of specific angiotensin II receptors increased in all regions during the first 2 weeks of life and then decreased to adult levels. Peak numbers of receptors were up to 10 times the adult numbers.

3. The midbrain and thalamus-hypothalamus had maximum numbers of angiotensin II receptors at 2 weeks of age, whereas the rest of the brain regions had maximum numbers at 1 week.

4. Saralasin-infusion experiments suggested that circulating angiotensin-related peptides could reach brain angiotensin II receptors in 2 week old rats, but not in 6 week old rats.

5. It is postulated that the centrally mediated actions of circulating angiotensin II may be particularly important in the newborn.
Hormonal Changes with Long-Term Converting-Enzyme Inhibition by Captopril in Essential Hypertension
Authors: Matthews P. G. , McGrath B. P. , Johnston C. I.
Published: August 2015

1. Captopril was shown to be as effective as hydrochlorothiazide in lowering the blood pressure in patients with moderately severe essential hypertension.

2. With the combination of captopril and hydrochlorothiazide satisfactory control of blood pressure was maintained over 8 months.

3. Inhibition of angiotensin converting enzyme by captopril in man was associated with falls in plasma angiotensin II and urinary aldosterone and rises in angiotensin I and plasma renin.

4. No change in venous concentrations of bradykinin could be demonstrated during therapy.

5. Captopril attenuated the hyperaldosteronism and hypokalaemia associated with diuretic therapy.
A Novel Orally Active Converting-Enzyme Inhibitor Ys 980: Effects on Blood Pressure in Spontaneously Hypertensive Rats
Authors: Unger Th. , Rockhold R. W. , Schaz K. , Vescei P. , Bönner G. , Rascher W. , Ganten D.
Published: August 2015

1. The effects of long-term treatment with the angiotensin I converting-enzyme inhibitor YS 980 were examined in stroke-prone spontaneously hypertensive (sp-SH) rats. Development of hypertension was markedly blunted in the YS 980-treated animals.

2. Effective converting-enzyme inhibition was confirmed by significant increases in plasma angiotensin I (ANG I) and plasma renin concentration, inhibition of the pressor responses to intravenous ANG I and potentiation of the depressor responses to intravenous bradykinin.

3. Urinary free aldosterone excretion was decreased but no changes in urinary sodium and potassium excretion were observed.

4. The pressor responses to intravenous leucine-enkephalin were reduced.

5. The pressor responses to injection of ANG I and bradykinin into the lateral brain ventricle were unaltered.

6. We conclude that the antihypertensive action of YS 980 in sp-SH rats cannot be explained by the inhibition of the plasma renin-angiotensin system alone. Effects on other peptide systems must be considered.
α-Adrenergic Suppression of Renin Secretion in the Rat Independent of Renal Vasoconstriction
Authors: Vandongen R. , Strang K. D. , Poesse Marianne H. , Birkenhager W. H.
Published: August 2015

1. The effect of α-adrenergic stimulation, with phenylephrine, on isoprenaline-provoked renin secretion was studied in the isolated perfused rat kidney.

2. Infusion of phenylephrine increased renal perfusion pressure and prevented renin secretion in response to isoprenaline.

3. Renal vasoconstriction was abolished and the response in renin secretion to isoprenaline was restored by α-adrenoreceptor blockade with phenoxybenzamine.

4. In contrast, when renal vasoconstriction was prevented by dihydrallazine, suppression of renin release by phenylephrine still occurred.

5. These observations support an inhibitory effect of a non-vascular α-adrenergic mechanism on renin release. It is suggested that the α-receptor mediating this effect is directly related to the renin-producing juxtaglomerular cell.
Plasma Catecholamines and Blood Pressure Responses to the Carotid Baroreceptor Reflex in Essential Hypertension
Authors: Mancia G. , Leonetti G. , Picotti G. B. , Ferrari A. , Galva M. D. , Gregorini L. , Parati G. , Pomidossi G. , Ravazzani C. , Sala C. , Zanchetti A.
Published: August 2015

1. Slight decreases and increases in carotid baroreceptor activity were induced in subjects with essential hypertension by slight alterations in carotid transmural pressure (variable pressure neck-chamber technique) in order to obtain limited increases and reductions in sympathetic adrenergic activity.

2. When sympathetic activity was reflexly increased there was a rise in arterial pressure but no significant increase in plasma catecholamines. Likewise when sympathetic activity was reflexly reduced there was a fall in arterial pressure but no significant reduction in plasma catecholamines.

3. Plasma noradrenaline and adrenaline significantly and markedly increased in the same subjects when sympathetic activity was increased by activation of both arterial and low pressure baroreceptor reflexes with tilting.

4. It is suggested that measurements of catecholamines in systemic plasma may reveal marked degrees of sympathetic activation but may not be a sensitive index of more moderate changes in sympathetic tone.
Increased Plasma and Urinary Normetanephrine in Young Patients with Primary Hypertension
Authors: Kobayashi K. , Kolloch R. , DeQuattro V. , Miano L.
Published: August 2015

1. Normetanephrine was measured in small samples of plasma and urine of hypertensive patients and normal volunteers (age 20–60 years) by a specific radioenzymatic assay with bovine adrenal phenylethanolamine N-methyltransferase and tritiated S-adenosylmethionine.

2. Noradrenaline was measured simultaneously in plasma and urine.

3. Plasma normetanephrine and noradrenaline concentrations varied in direct proportion to activation or suppression of sympathetic nerve function.

4. Both plasma and urinary normetanephrine concentrations were elevated in patients with phaeochromocytoma.

5. Plasma normetanephrine concentrations were related to plasma noradrenaline concentrations of hypertensive subjects.

6. Plasma normetanephrine and noradrenaline concentrations and urinary normetanephrine excretion rates were increased in some young patients with primary hypertension, suggesting that sympathetic nerve hyperactivity is a pathogenic factor in these patients.
Plasma Noradrenaline Concentration in Hypertensive and Normotensive 40-Year-Old Individuals: Relationship to Plasma Renin Concentration
Authors: Ibsen H. , Christensen N. J. , Hollnagel H. , Leth A. , Kappelgaard A. M. , Giese J.
Published: August 2015

1. Forty-year-old individuals with mild essential hypertension, identified during a survey of a population born in 1936, were investigated. Forty-year-old normotensive subjects, drawn from the same population, served as a control group.

2. Plasma noradrenaline concentration and plasma renin concentration at rest supine and after acute stimulation, as induced by frusemide intravenously and ambulation, did not differ from reference values in the 40-year-old normotensive controls. In the hypertensive group a close correlation (r = 0·77, P < 0·001) was found between plasma noradrenaline and plasma renin concentration after acute stimulation.

3. Sympathetic nerve activity, as defined by measurements of plasma noradrenaline, is normal in mild essential hypertension. Discrepancies described in the literature are probably related to a lack of comparability between hypertensive and normotensive study populations.
Effect of the α-Adrenoreceptor Agonist Ld 3098 (Cirazoline) on the Magnitude of End-Organ Responses Induced by Nerve Stimulation and Exogenous Noradrenaline in a Variety of Sympathetically Innervated Animal Tissues
Authors: Massingham R. , Dubocovich Margarita L. , Langer S. Z.
Published: August 2015

1. Previous studies have shown that LD 3098 (cirazoline), a potent directly acting α-adrenoreceptor agonist, failed to antagonize heart rate increases induced by ansa subclavia stimulation in anaesthetized dogs. However, in the isolated perfused cat spleen LD 3098 inhibited transmitter release elicited by nerve stimulation and behaved as a preferential presynaptic α-adrenoreceptor agonist.

2. LD 3098 (0·01–10 μmol/l) increased the twitch response of the isolated rat vas deferens to field stimulation. However, preincubation of the tissue with prazosin (0·1 μmol/l) unmasked a presynaptic inhibitory effect of LD 3098, which was antagonized by yohimbine.

3. LD 3098 was a full agonist in isolated dog saphenous veins and in low concentrations (0·01 μmol/l) shifted the concentration—response curves to noradrenaline, potasium (K+) and prostaglandin F2α (PGF2α) to the left without changing the maximum response. Furthermore the potentiating effect of LD 3098 on PGF2α responses was antagonized by prazosin (0·1 μmol/l).

4. It is concluded that LD 3098 produces a non-specific sensitization of vascular smooth muscle by acting on postsynaptic α-adrenoreceptors.

5. This increase in end-organ sensitivity might explain why LD 3098 appears as an α-adrenoreceptor agonist with preferential affinity for postsynaptic receptors when end-organ responses to nerve stimulation are measured and yet it is a preferential presynaptic agonist in 3H-labelled transmitter-release studies. Such findings further emphasize the need for caution when assessing presynaptic activity indirectly via end-organ response to nerve stimulation.
Effect of Neonatal Sympathectomy by 6-Hydroxydopamine on Volume and Resistance Regulation in Stroke-Prone Spontaneously Hypertensive Rats
Authors: Schömig A. , Dietz R. , Rascher W. , Ebser H. , Voss U. , Gross F.
Published: August 2015

1. Neonatal sympathectomy with 6 hydroxydopamine (6-OHDA) was used as a tool to assess the significance of an increased sympathetic vascular tone for the development of high blood pressure in stroke-prone spontaneously hypertensive rats. After administration of 6-OHDA the rise in blood pressure was blunted for the following 9 weeks until innervation was re-established. 6-OHDA-treated rats retained more sodium and had larger plasma and blood volumes than sham-treated rats.

2. Catecholamines in plasma were increased 2–10-fold immediately after sympathectomy, but their concentrations were subnormal on day 7. Eight weeks after sympathectomy plasma noradrenaline and dopamine were not elevated, but plasma adrenaline has increased twofold.

3. The reactivity of resistance vessels to noradrenaline was markedly enhanced and the neuronal uptake and metabolism of noradrenaline were still reduced 8 weeks after neonatal sympathectomy.

4. These results confirm the significance of an intact sympathetic nervous system for the development in these rats. Sodium retention and increased plasma and blood volume may be considered as a compensatory mechanism for the vasodilatation resulting from decreased vasomotor tone.
The Effect of Mental Stress on Catecholamines, their Metabolites and Plasma Renin Activity in Patients with Essential Hypertension and in Healthy Subjects
Authors: Januszewicz W. , Sznajderman M. , Wocial B. , Feltynowski T. , Klonowicz T.
Published: August 2015

1. Ten patients with essential hypertension and ten healthy men were submitted to mental stress consisting of Kraepelin's arithmetic test combined with noise. Concentrations of plasma and urine catecholamines and of their metabolites as well as plasma renin activity before and after the test were studied.

2. In both groups a significant increase of noradrenaline and adrenaline in blood and noradrenaline in urine was observed. The urinary excretion of dopamine fell significantly in both groups after stress.

3. After mental stress a significant increase in urinary excretion of 3-methoxy-4-hydroxyphenylglycol was observed in both groups. The excretion of vanillylmandelic acid decreased significantly only in healthy subjects.

4. The plasma renin activity rose significantly in both groups but the increase was more pronounced in healthy subjects.
Enhanced Release of Noradrenaline in the Kidney of the Young Spontaneously Hypertensive Rat
Authors: Collis M. G. , de Mey C. , Vanhoutte P. M.
Published: August 2015

1. Vascular reactivity and noradrenaline overflow were studied in Tyrode solution-perfused kidneys from young (6 weeks) normotensive and spontaneously hypertensive (SH) rats.

2. The vasoconstrictor response to nerve stimulation was greater in the kidneys from young SH rats than in those from young control rats.

3. Nerve stimulation evoked a greater release of noradrenaline in the kidneys from young SH rats than in those from normotensive animals.

4. The results demonstrate that the renal sympathetic nerves release more noradrenaline than normal in the young SH rats, which could be an important factor in causing hypertension.
Modulation of Sympathetic Vascular Tone by Prostaglandins in Corticosterone-Induced Hypertension in Rats
Authors: Rascher W. , Dietz R. , Schömig A. , Burkart G. , Lüth J. B. , Mann J. F. E. , Weber J.
Published: August 2015

1. In corticosterone-induced hypertension in rats the activity of the peripheral sympathetic nervous system and its modulation by prostaglandins was studied.

2. Plasma concentrations of noradrenaline were reduced if compared with those in normotensive control rats.

3. The sensitivity of the isolated perfused hindlimb preparation to noradrenaline was enhanced before blood pressure rose and increased further with the development of hypertension.

4. Arachidonic acid, prostacyclin (prostaglandin I2), but not 6-keto-prostaglandin F1α, reversed the supersensitivity to noradrenaline.

5. These results suggest that corticosterone induces a supersensitivity to noradrenaline by inhibiting the biosynthesis of prostaglandins. Changes in the sensitivity of the vascular smooth muscle may play a role in the development of glucocorticoid hypertension.
Urinary Kallikrein in Normotensive Subjects and in Patients with Essential Hypertension
Authors: Zschiedrich H. , Fleckenstein P. , Geiger R. , Fink E. , Sinterhauf K. , Philipp TH. , Distler A. , Wolff H. P.
Published: August 2015

1. Excretion of urinary kallikrein was normal in 13 out of 15 patients with uncomplicated essential hypertension.

2. Frusemide increased urinary kallikrein excretion in normotensive subjects and in patients with essential hypertension. The stimulating effect of frusemide on urinary kallikrein was significantly diminished in patients with essential hypertension.

3. No correlations of urinary kallikrein with sodium, potassium, and aldosterone excretion were found.

4. The results do not support the idea that urinary kallikrein plays a primary role in the pathogenesis of essential hypertension.
Urinary Prostaglandins and Kallikrein in Essential Hypertension
Authors: Weber P. C. , Scherer B. , Held E. , Siess W. , Stoffel H.
Published: August 2015

1. Urinary prostaglandins (PG), kallikrein and plasma renin activity (PRA) were measured in 35 patients with essential hypertension and 22 normotensive controls before and 15 min after frusemide (40 mg intravenously).

2. PGE2 and kallikrein excretion rates were lower in hypertensive subjects, and failed to rise to the same extent after frusemide. PGF2α excretion was not significantly different in the two groups of patients either before or after frusemide. PRA rose less in the hypertensive subjects after frusemide.

3. These findings support the view that there is an abnormality of renal vasodilator systems (PGE2 and kallikrein) in essential hypertension.
Sodium Balance, Urinary Prostaglandin E2 and Renin in Normal Man
Authors: Nielsen I. , Elmgreen J. , Christensen P. , Hesse B.
Published: August 2015

1. Urinary prostaglandin (PG) E2 excretion and plasma renin were measured in five healthy volunteer subjects for 2 h after intravenous injection of frusemide (protocol A) and during salt restriction for 7 days with frusemide added on the 2 last days (protocol B).

2. In protocol A, peak values in PGE2 and urine flow were reached in 10–20 min, after which the values rapidly subsided. Plasma renin increased twofold in 60 min.

3. In protocol B, even during severe anti-natriuresis (day 5) and during maximal negative sodium balance (day 7), no change in urinary PGE2 excretion was observed. Plasma renin increased twofold on day 5 and increased tenfold on day 7.

4. The result of protocol B does not suggest any essential role of renal PGE2 for sodium excretion or sodium homeostasis in man. The result of protocol A may point to a role of renal prostaglandins for the diuretic action of frusemide.
Factors Influencing Blood Pressure in Chronic Alcoholics
Authors: Saunders J. B. , Beevers D. G. , Paton A.
Published: August 2015

1. Of 96 alcoholics admitted for detoxification, 48% were hypertensive (systolic blood pressure > 140 mmHg and/or diastolic pressure > 90 mmHg).

2. Elevation of both systolic and diastolic blood pressures was related to the severity of alcohol-withdrawal symptoms.

3. After these symptoms had abated only 9% of patients remained hypertensive.

4. Blood pressure remained normal if patients abstained from alcohol after discharge but rose in those who started drinking again.

5. Hypertension was not consistently related to the presence or severity of alcoholic liver disease.

6. Alcohol-related hypertension may be the result of the alcohol-withdrawal syndrome; increased noradrenergic activity is suggested as the likely mechanism.
Responsiveness to Prazosin in Renal Failure
Authors: Stokes G. S. , Monaghan J. C. , Frost G. W. , MacCarthy E. P.
Published: August 2015

1. The fall in blood pressure produced by a test dose of prazosin was greater in a group of patients with chronic renal failure than in a group with normal renal function.

2. This difference could not be attributed to increased reactivity, measured as the slope of the regression line relating mean blood pressure and plasma prazosin concentration, nor to retarded elimination of the drug.

3. The enhanced antihypertensive effect of prazosin in renal failure appears to reflect changes in the bioavailability or distribution of the drug, which result in higher drug concentrations for a given dose.
Influence of Selective and Non-Selective β-Adrenoreceptor Blockade on the Haemodynamic Effect of Adrenaline during Combined Antihypertensive Drug Therapy
Authors: Houben H. , Thien TH. , De Boo TH. , Lemmens W. , Van Herwaarden C. L. A. , Fennis J. F. M. , Van 'T Laar A.
Published: August 2015

1. Haemodynamic effects of adrenaline were studied in 27 hypertensive patients, successively during treatment with propranolol and metoprolol. In 12 patients β-adrenoreceptor blockade was combined with diuretics and in 15 patients the blockade was combined with vasodilators.

2. During propranolol adrenaline caused a marked pressor effect: there was a considerable rise in systolic as well as in diastolic blood pressure and a marked fall in heart rate. During metoprolol there was only a slight rise in blood pressure and an increase in heart rate.

3. Forearm blood flow was decreased by adrenaline during propranolol and was increased during metoprolol. Calculated vascular resistance showed opposite changes.

4. Results were essentially the same when β-adrenoreceptor blockade was combined with diuretics or with vasodilators and did not differ from previous results obtained in patients treated by blockade alone.

5. If adrenaline infusion can be considered as a model for acute stress, our results seem to favour a selective β-adrenoreceptor blocking agent over a non-selective one, even when the blocker is combined with a diuretic or a vasodilator.
Long-term Effect of Sotalol on Plasma Lipids
Authors: Lehtonen A. , Viikari J.
Published: August 2015

1. We studied the effect on plasma lipids of sotalol given orally over a 12 month period to patients with essential hypertension.

2. Plasma free fatty acid concentration was lower than initially at 1, 3, 6 and 12 months. The difference was significant (P < 0·01) at 1 and 3 months.

3. Plasma cholesterol (VLDL + LDL-cholesterol) increased during treatment. Plasma total cholesterol increased from 5·49 ± sd 0·94 mmol/l at the beginning to 6·37 ± 1·10 mmol/l at 12 months (P < 0·01).

4. HDL-cholesterol concentration and the ratio of HDL-cholesterol to total cholesterol decreased significantly. The ratios were 0·28 and 0·18 at the beginning and at 12 months respectively (P < 0·001).

5. Plasma triglycerides increased simultaneously from 1·14 ± 0·31 to 1·89 ± 0·99 mmol/l (P < 0·01).
Observations on Some Properties of a Long-Acting Preparation of Propranolol
Authors: Shanks R. G. , Neill J. D. , Leahey W. J. , Varma M. P. S.
Published: August 2015

1. The effects of 160 mg of propranolol and 160 mg of a long-acting (LA) formulation of propranolol were studied in healthy subjects.

2. Both drugs reduced an exercise tachycardia but the peak was less and the 24 h effect greater after long-acting propranolol than after propranolol.

3. These differences were maintained on repeated dosing for 8 days.

4. In contrast to single doses of 400 mg of sotalol, 160 mg of oxprenolol and 160 mg of slow-release oxprenolol, the peak effect of long-acting propranolol was less and that at 24 h was greater.
Intraluminal Dilatation of Renal Artery Stenosis
Authors: Geyskes G. G. , Puylaert C. B. A. J. , Oei H. Y. , Boomsma J. H. B.
Published: August 2015

1. In 13 patients with hypertension and renal artery stenosis the stenosis was dilated by an intra-arterial balloon catheter under local anaesthesia.

2. In all but one instance arteriography after the dilatation showed considerable widening of the stenosed area.

3. Six patients had a temporary increase of serum creatinine that lasted only a few days.

4. In seven patients, who had a prolonged transit time at renography, this marker of renal blood flow improved after the dilatation.

5. The effect of the dilatation on the blood pressure in this group of patients, selected on arteriographic criteria only, was variable, but comparable with results of renovascular surgery.

6. Dilatation of renal artery stenosis by an intra-arterial balloon catheter is a promising treatment for patients with hypertension and renal artery stenosis. It is a rapid procedure needing only local anaesthesia. Complications in our experience so far are minor.