bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Phosphate Adaptation in Uraemic Dogs with a Remnant Kidney
Authors: Wen S.-F. , Stoll R. W.
Published: August 2015

1. Clearance and micropuncture studies were performed in 27 dogs made uraemic by segmental infarction to examine the factors responsible for phosphate adaptation in chronic renal failure.

2. The animals were studied before and after extracellular volume expansion to 10% of body weight in the presence and absence of parathyroid glands. The results were compared with 19 normal dogs studied under similar experimental conditions.

3. In the dogs with a remnant kidney and intact parathyroids adaptation of phosphate transport was evident, with a high fractional excretion of phosphate. Thyroparathyroidectomy 3 days before study in the dogs with a remnant kidney and moderate renal failure reduced fractional excretion of phosphate to near normal values, indicating a major role of parathyroid hormone in phosphate adaptation. Extracellular volume expansion in these thyroparathyroidectomized uraemic dogs led to an exaggerated phosphaturic response with fractional excretion of phosphate returning towards the value in the uraemic dogs with intact parathyroid glands. Thus acute extracellular volume expansion could also contribute to the increase in fractional phosphate excretion, but extracellular volume probably plays a relatively minor role in the adaptation of phosphate excretion.

4. With more advanced renal failure fractional excretion of phosphate remained high, even after thyroparathyroidectomy, indicating that parathyroid hormone-independent factors become important for phosphate adaptation in the advanced stage of renal failure. The nature of parathyroid hormone-independent changes in fractional phosphate reabsorption in chronic renal failure remains unknown.

5. Proximal tubular fluid/plasma ultrafiltrate phosphate ratios were high in all groups of dogs with a remnant kidney regardless of thyroparathyroidectomy or the degree of renal failure. The non-specific nature of the proximal tubule pattern of phosphate transport indicates that phosphate adaptation is primarily determined by alterations in phosphate transport at a site distal to the proximal convoluted tubule. Alternatively, deep nephrons may play a greater role in determination of the overall phosphate adaptation in the chronically diseased kidney.
Lipid Peroxidation in Iron-Overloaded Spleens
Authors: Heys A. D. , Dormandy T. L.
Published: August 2015

1. Iron-overloaded spleens from thalassaemic subjects showed a greatly increased susceptibility to free-radical oxidation (peroxidation) in vitro.

2. Iron content was the main but not the only variable governing susceptibility. Added ascorbate had a dose-dependent action either as an antioxidant or as a pro-oxidant, the direction of its effect depending mainly on the degree of iron overload. This has therapeutic implications.
Age-Related Decrease in Cardiac and Peripheral Vascular Responsiveness to Isoprenaline: Studies in Normal Subjects
Authors: Van Brummelen P. , Bühler F. R. , Kiowski W. , Amann F. W.
Published: August 2015

1. Changes in forearm blood flow to intra-arterial infusion of isoprenaline and the chronotropic response to intravenous boluses of isoprenaline were measured in 15 healthy volunteer subjects, eight younger than 25 years and seven older than 50 years. Intra-arterial blood pressure and basal plasma renin activity, adrenaline and noradrenaline were also measured.

2. Young subjects exhibited a greater increase in forearm blood flow than old subjects, to all four doses of isoprenaline used, a greater cardiac isoprenaline responsiveness (measured by the increase in heart rate; P<0.001) and a higher renin (P<0.02).

3. Resting values of blood pressure, forearm blood flow, adrenaline and noradrenaline were not significantly different in young and old subjects. In the latter, noradrenaline correlated with forearm blood flow (r = −0.77, P<0.05), forearm vascular resistance (r = 0.86, P<0.02) and mean arterial pressure (r = 0.83, P<0.02), whereas in the younger subjects forearm blood flow was related to adrenaline (r = 0.78, P<0.05).

4. These data provide evidence for an age-related parallel reduction in cardiac, peripheral vascular and renal β-adrenoceptor-mediated responses.
The Relative Amounts of the Collagen Chains α1(I), α2 and α1(III) in the Skin of 31 Patients with Osteogenesis Imperfecta
Authors: Francis M. J. O. , Williams K. J. , Sykes B. C. , Smith R.
Published: August 2015

1. The relative amounts of type III and type I collagen, determined as the ratio of their constituent α1(III) and α1(I) chains, have been measured by interrupted electrophoresis of pepsin extracts of skin collagen from 31 patients with osteogenesis imperfecta of varying severity, and from six clinically unaffected family members. In 18 patients the ratio of the α1(I) to α2 chains of type I collagen has also been measured.

2. In the 15 patients with osteogenesis imperfecta classified as mild or the 18 with type I disease the ratio α1 (III)/α1 (I) was significantly increased (P < 0.001) and the ratio α1(I)/α2 significantly decreased (P < 0.005) compared with age-matched control subjects.

3. In three infants with lethal (type II) osteogenesis imperfecta the ratio α1(III)/α1 (I) was normal, contrasting with the high ratio observed by others in fibroblast cultures from some apparently similar patients.

4. The ratio of α1(I)/α2 and of α1(III)/α2(I) was increased in both clinically normal parents of a child with severe disease, and in the mother of two children with osteogenesis imperfecta (one lethal and one severe) the ratio α1(III)/α1 (I) was increased.

5. In the remaining patients with severe bone deformity (types III and IV) the relative amounts of the different collagen chains varied.

6. These data support previous suggestions that mild or type I osteogenesis imperfecta results from a generalized inability to form sufficient type I collagen, the predominant collagen of adult bone, and imply that in many cases this may result from defective production of the α1(I) chain rather than of the α2 chain. Some patients with severe disease demonstrate a similar defect; but in the remainder other abnormalities of collagen or connective tissue maturation are presumably involved.
Systemic and Forearm Haemodynamic and Metabolic Effects of Racemic Propranolol or d-Propranolol in Healthy Subjects
Authors: Hartling O. J. , Svendsen T. Lysbo , Trap-Jensen J.
Published: August 2015

1. The immediate haemodynamic and metabolic effects of intravenous administration of dl-propranolol and d-propranolol were studied in healthy male subjects at rest and during dynamic forearm exercise. The dose of dl-propranolol and of d-propranolol was 0.1 and 1.0 mg/kg body weight respectively.

2. dl-Propranolol reduced heart rate significantly at rest, during forearm exercise and post-exercise, whereas d-propranolol had a lesser effect on heart rate which was significant only at the end of the exercise period. Arterial blood pressure and forearm blood flow were unchanged after either drug.

3. Both drugs reduced the release of lactate from the exercising forearm. Forearm exchange of oxygen, glucose, free fatty acids and triglycerides remained unchanged.

4. The arterial blood glucose concentration increased after d-propranolol, but was unchanged after dl-propranolol. The arterial serum free fatty acid concentration decreased after dl-propranolol, but was not changed after d-propranolol. Arterial concentrations of lactate and triglycerides were not influenced by the drugs.

5. The chronotropic response to β-adrenoceptor blockade appears to be stereoselective, suggesting specific blockade of β-adrenoceptors. Metabolic responses to β-adrenoceptor blockade are difficult to explain in terms of the known adrenoceptor system and may be due to nonspecific actions of β-adrenoceptor antagonists. An exception is inhibition of lipolysis, which is probably mediated via β-adrenoceptors.
An Increase in a Circulating Inhibitor of Na+,K+-Dependent ATPase: A Possible Link between Salt Intake and the Development of Essential Hypertension
Authors: MacGregor G. A. , Fenton S. , Alaghband-Zadeh J. , Markandu N. D. , Roulston J. E. , De Wardener H. E.
Published: August 2015

1. The plasma's ability to stimulate guinea-pig renal glucose 6-phosphate dehydrogenase (G6PD) in vitro was measured by a cytochemical technique in 23 normotensive subjects and 19 patients with hypertension, all of whom were studied on their normal sodium intake. The ability of plasma to stimulate renal G6PD was significantly (P < 0.001) increased in the hypertensive patients (mean 195 ± 52 units/ml) compared with the normotensive subjects (mean 22.2 ± 5.8 units/ml). In all 42 individuals, there was a significant correlation between diastolic pressure and the ability of plasma to stimulate G6PD (r = 0.69 P < 0.001).

2. The ability of plasma to stimulate G6PD was greatest in the hypertensive patients with values of plasma renin activity below the normal range. In the normotensive subjects the ability of plasma to stimulate G6PD was significantly greater in the older subjects.

3. As the ability of plasma to stimulate G6PD reflects its ability to inhibit Na+,K+-dependent ATPase, these results suggest that patients with essential hypertension have an increase in a circulating inhibitor of Na+,K+-ATPase. The results support the hypothesis that a rise in a circulating sodium transport inhibitor may, in part, be responsible for the rise in blood pressure in essential hypertension, and may form the link between salt intake, abnormalities of sodium transport and a rise in blood pressure.
Study of the Carbohydrate Content of Mucus Glycoproteins from Normal and Diseased Colons
Authors: Clamp J. R. , Fraser G. , Read A. E.
Published: August 2015

1. Mucus samples obtained from colectomy colons from 10 patients with ulcerative colitis and four patients with Crohn's disease of the colon, together with samples from 10 normal postmortem colons, have been studied.

2. Two glycoprotein fractions were isolated from mucosal scrapings by gel-permeation chromatography. The high-molecular-weight fraction consisted largely of mucus glycoproteins and was further purified to the glycopolypeptides. The low-molecular-weight fraction contained a glycoprotein with a high mannose content. The carbohydrate content of both the mucus glycoprotein and glycopolypeptide fractions were significantly reduced in active colitis.

3. Oligosaccharides were prepared from the mucus glycoprotein material. In the normal material more than half the units contained eight or more monosaccharide residues, whereas in the disease material the bulk of the units were smaller than this.
Effects of Clonidine on Aortic Pressure-Diameter and Elastic Stiffness-Stress Relations in Anaesthetized Rabbits
Authors: Friggi A. , Bodard H.
Published: August 2015

1. The effects of clonidine on the aortic pressure-diameter relationship were studied in anaesthetized rabbits by means of an ultrasonic dimension technique. Midwall aortic stress and aortic elastic modulus were calculated.

2. In spite of a significant decrease in mean aortic blood pressure, aortic diameter was slightly but not significantly increased after intravenous clonidine injection (25 μg/kg body wt., intravenously over 30 s).

3. Midwall aortic stress was decreased when compared at the same aortic radius and aortic elastic modulus was increased when compared at a common blood pressure level. However, when aortic elastic modulus was plotted as a linear function of the stress, no difference was observed before and after clonidine.

4. The results suggest that the pressure-diameter changes induced by clonidine were primarily reflecting the mechanical changes in the aortic wall due to changes in smooth muscle tension. Furthermore it seems that the elastic modulus of the aorta tends to remain constant by adaptive changes in the aortic wall which over-ride the concurrent geometrical changes to maintain a level of elasticity consistent with the degree of aortic stress.
Plasma and Interstitial Volumes in Essential Hypertension: Relationship to Blood Pressure
Authors: Bing R. F. , Smith A. J.
Published: August 2015

1. Plasma and interstitial fluid volumes have been measured simultaneously in men with uncomplicated and untreated essential hypertension.

2. Plasma volume (Evans blue) was reduced in essential hypertension and correlated inversely with blood pressure.

3. Interstitial fluid volume, derived from bromine space and plasma volume, was also reduced in essential hypertension and correlated inversely with blood pressure. The mean reduction in both plasma and interstitial fluid volumes was 6–7%.

4. There is no evidence for volume expansion in essential hypertension and the relationship between plasma and interstitial fluid volumes is preserved. The contraction of plasma and interstitial fluid volumes is most likely to reflect a natriuresis and diuresis secondary to the raised renal perfusion pressure, and sodium retention is unlikely to be a primary event in essential hypertension.
Effect of β-Adrenoceptor Blockade on Exercise Performance and Metabolism
Authors: Lundborg PER , Åström H. , Bengtsson C. , Fellenius E. , Von Schenck H. , Svensson L. , Smith U.
Published: August 2015

1. Carbohydrate and lipid metabolism and the capacity to perform prolonged submaximal physical exercise were studied in six young healthy subjects treated in a randomized double-blind fashion for 2 days with either placebo, the non-selective β-adrenoceptor antagonist propranolol (80 mg b.i.d.) or the cardioselective agent metoprolol (100 mg b.i.d.). On day 3, 1 h after the last dose, the subjects exercised for 30 min periods followed up 10 min rest up to the point of exhaustion.

2. The capacity to perform exercise was decreased with both β-adrenoceptor antagonists. However, at an equal degree of β1-adrenoceptor blockade, all subjects could exercise for a longer period of time on the cardioselective agent as compared with the non-selective drug.

3. Blood glucose levels decreased during exercise irrespective of the type of treatment, but the attenuation occurred most rapidly on propranolol. At exhaustion the average non-esterified fatty acid levels had increased 256% on placebo, 148% on metoprolol and 65% on propranolol. A significant positive correlation was found between changes in non-esterified fatty acid levels during exercise and total working time. It is concluded that β-adrenoceptor blockade diminishes the capacity for prolonged submaximal exercise at least in part by reducing the availability of substrates to the working muscles.
Dietary Sodium, Erythrocyte Sodium Concentration, Sodium-Stimulated Lithium Efflux and Blood Pressure
Authors: Trevisan M. , Cooper R. , Ostrow D. , Miller W. , Sparks S. , Leonas Y. , Allen A. , Steinhauer M. , Stamler J.
Published: August 2015

1. There was a significant positive relationship between sodium-stimulated lithium efflux and systolic blood pressure (r = 0.512) in erythrocytes of black school children. Weight was also positively and significantly correlated with blood pressure. Although erythrocyte sodium concentration did not bear any significant relationship with blood pressure, it did bear significant inverse relationship with urinary sodium excretion.

2. High-school students were randomly assigned to either the experimental or the control group. In the former a reduction of about 70% in salt intake was achieved. After 24 days, the erythrocyte sodium concentration was significantly reduced in the experimental group. A non-significant decline in systolic blood pressure was observed in the experimental group; no change was detectable in the control group for either erythrocyte sodium concentration or systolic blood pressure.
A Comparison of Radioactive Calcium Absorption Tests with Net Calcium Absorption
Authors: Marshall D. H. , Nordin B. E. C.
Published: August 2015

1. Four different methods of calculating calcium absorption by radioactive calcium procedures have been compared with each other and with net calcium absorption in calcium-balance studies in 100 consecutive studies on 71 patients.

2. All four isotope procedures yielded highly significant correlations with net calcium absorption derived from the balance studies, but there was little to choose between the validity of the double-isotope and single-isotope procedure judged by these criteria.

3. The rate of calcium absorption calculated from one or other isotope procedure correlated better with net calcium absorption than did the fraction of the radioactive calcium absorbed.

4. The measurement of plasma radioactivity 1 h after single-isotope administration, corrected for body weight, proved almost as useful as the more complex procedures but would be expected to underestimate calcium absorption in states of very high bone turnover.
Studies on the Role of a Humoral Sodium-Transport Inhibitor and the Anteroventral Third Ventricle (AV3V) in Experimental Low-Renin Hypertension
Authors: Pamnani M. B. , Buggy J. , Huot S. J. , Haddy F. J.
Published: August 2015

1. Recent studies in our laboratory suggest that Na+,K+-dependent-ATPase and Na+—K+ pump activities are reduced in cardiovascular muscle of animals with experimental low-renin hypertension.

2. We here show that these abnormalities are associated with a heat-stable ouabain-like agent in the plasma.

3. In the volume-expanded rat, an anteroventral third ventricle (AV3V) lesion decreases the level of the ouabain-like humoral factor and increases vascular Na+—K+ pump activity. These findings suggest that the humoral ouabain-like factor originates in or is influenced by the AV3V area of the brain and may help to explain why the AV3V lesion prevents or reverses one-kidney renal and one-kidney, DOCA—salt hypertension in rats.
Contribution of Stenosis Resistance to the Rise in total Peripheral Resistance during Experimental Renal Hypertension in Conscious Dogs
Authors: Anderson W. P. , Korner P. I. , Angus J. A. , Johnston C. I.
Published: August 2015

1. Mild, moderate and severe renal artery stenosis was induced in uninephrectomized conscious dogs by inflating a renal artery cuff to lower distal pressure to 60, 40 or 20 mmHg respectively. The renal artery was narrowed progressively over the next 3 days by further inflation of the cuff to relower the distal renal artery pressure to the initial values.

2. Graded progressive stenosis produced graded progressive rises in blood pressure, plasma renin activity and total renal resistance to flow over the 3 day period, followed by a return to control values 24 h after cuff deflation.

3. The rise in total renal resistance to flow was almost entirely due to the stenosis, with only small changes occurring in renal vascular resistance.

4. in moderate and severe stenosis cardiac output did not alter significantly and thus increases in blood pressure were due to increases in total peripheral resistance. in these groups the resistance to blood flow of the stenosis accounted respectively for about 36 and 26% of the rises in total peripheral resistance. Vasoconstriction of the other non-renal vascular beds accounted for the remainder of the increase in total peripheral resistance.

5. in mild stenosis the changes in both cardiac output and total peripheral resistance were variable and not statistically significant. in this group the rise in stenosis resistance was compensated by vasodilatation of the non-renal vascular beds.

6. in all groups rises in plasma renin activity and blood pressure correlated with the haemodynamic severity of the stenosis.

7. Thus the resistance to blood flow of the moderate and severe renal artery stenoses accounted for one-quarter to one-third of the increases in total peripheral resistance. The remainder of the increase in total peripheral resistance was due to vasoconstriction of nonrenal beds.
Urinary Excretion of Bile Acids in Cholestasis: Evidence for Renal Tubular Secretion in Man
Authors: Corbett C. L. , Bartholomew T. C. , Billing Barbara H. , Summerfield J. A.
Published: August 2015

1. the apparent renal clearance of intravenously injected [14C]glycocholate and [3H]-chenodeoxycholate-3-sulphate was estimated in 22 patients with cholestasis. the degree of protein binding of the isotopes in serum from these patients was determined. the effects of pharmacological agents, changes in urine flow rate and pH on renal clearance were studied.

2. the mean renal clearance of [14C]glycocholate was 1.7 ± 0.4 ml/min (mean ± sem), and that of [3H]chenodeoxycholate-3-sulphate was 6.4 ± 0.9 ml/min. [14C]Glycocholate was 80.1% protein bound and [3H]chenodeoxycholate-3-sulphate 96.5% protein bound.

3. Comparisons of the observed clearance rates with those calculated on the basis of glomerular filtration of the unbound fraction suggest that whereas [14C]glycocholate is predominantly reabsorbed by the renal tubules, [3H]chenodeoxycholate-3-sulphate appears in the urine mainly as the result of tubular secretion.

4. Probenecid, ethacrynic acid, frusemide and bendrofluazide decreased the clearance of both bile acids, implying competition for secretion via the proximal tubular organic acid secretory pathway between these compounds and bile acids.

5. Passive non-ionic diffusion does not seem to be an important mechanism in the renal excretion of bile acids as changes in urine flow rate and pH did not influence bile acid clearance.

6. A greater affinity of the proximal tubular organic acid secretory pathway for sulphated than for non-sulphated bile acids may explain the higher observed renal clearance rate of sulphated bile acids.
Complex Competitive and Non-Competitive Inhibition of Rat Lung Angiotensin-Converting Enzyme by Inhibitors Containing Thiol Groups: Captopril and SA 446
Authors: Mendelsohn F. A. O. , Csicsmann J. , Hutchinson J. S.
Published: August 2015

1. The kinetics of the inhibitory action of four different angiotensin-converting enzyme inhibitors was evaluated in vitro with rat lung enzyme and the substrate hippuryl-histidyl-leucine.

2. Enzyme velocity against substrate concentration curves were fitted directly to hyperbolae by a weighted least squares iterative method to obtain apparent values of Km, Vmax. and K/V at each concentration of inhibitor.

3. The inhibitory constants K1 and Kí were obtained by weighted linear regressions of K/V against i and 1/V against i respectively.

4. Teprotide was the least potent inhibitor with a K1 of near 20 nmol/l whereas captopril (SQ 14 225) and SA 446 were both approximately 10 times and MK 421 approximately 20 times more potent.

5. Two inhibitors which lacked thiol groups [teprotide or SQ 20 881 and N-(1-S-1-carboxy-3-phenylpropyl)-l-Ala-l-Pro or MK 421] produced a purely competitive pattern of inhibition with increased apparent Km but no change in apparent Vmax.

6. Two inhibitors containing thiol groups [captopril or SQ 14 225 and 2-(2′-hydroxyphenyl)-3-(3-mercaptopropanoyl)-4-thiazolidine carboxylic acid or SA 446] both produced a mixed competitive and non-competitive pattern of inhibition with increased apparent Km and decreased Vmax.

7. It is possible that thiol-containing inhibitors might produce non-competitive inhibition of converting enzyme by forming strong bonds with zinc near the active site of the enzyme.
Effect of Angiotensin II and Converting Enzyme Inhibitor (Captopril) on Blood Pressure, Plasma Renin Activity and Aldosterone in Primary Aldosteronism
Authors: Mantero F. , Fallo F. , Opocher G. , Armanini D. , Boscaro M. , Scaroni C.
Published: August 2015

1. Patients with idiopathic hyperaldosteronism (IHA) show a response of aldosterone to posture which is not present in patients with aldosterone-producing adenoma (APA). We have determined whether this could be explained by a different sensitivity to angiotensin II.

2. Angiotensin II was infused in gradually increasing doses in six patients with APA and in seven patients with IHA. No changes in aldosterone concentration were found at the end of each period in APA, whereas there was a significant increase in IHA; blood pressure rose by a similar extent in both groups.

3. In order to evaluate the role of endogenous angiotensin II, captopril, a converting enzyme inhibitor, was administered to six patients with APA and five patients with IHA at a dose of 75 mg/day for 1 week. There was a significant fall of mean blood pressure in IHA and only minimal changes in APA. Plasma renin activity and plasma and urinary aldosterone were unchanged in APA. In IHA there was a small increase in upright plasma renin activity and a slight decrease in both plasma and urinary aldosterone, but these changes were not significant.

4. These findings further support the idea that idiopathic hyperaldosteronism is a clinical state different from that occurring in primary aldosteronism due to adenoma, and may be more closely related to essential hypertension.
Optimum Tryptic Activation of Inactive Renin in Human Plasma is Independent of Endogenous Anti-Tryptic Activity
Authors: Rappelli Alessandro , Dessi'-Fulgheri Paolo , Madeddu Paolo , Meloni Franca , Fiori Caterina , Sanna Giovanni , Glorioso Nicola
Published: August 2015

1. Plasma samples from 31 normal subjects were treated (at 4°C, pH 7.0, for 2 min) with different concentrations of trypsin (500, 1000, 2000, 3000 and 4000 μg/ml) in order to assess which concentration yielded the maximum activation of inactive renin.

2. Endogenous antitryptic activity was also measured in all samples; the mean value ± sd (in μg of trypsin inhibited by 1 ml of plasma) was 953 ± 550 μg/ml (range 34–1800 μg/ml).

3. In the entire group of subjects the values of trypsin-activated renin measured with trypsin at 2000 μg/ml were significantly higher than those obtained with lower or higher trypsin concentrations.

4. With subjects divided into subgroups according to their endogenous anti-tryptic activity, the maximum yield of activation was reached with trypsin at 2000 μg/ml.

5. No significant correlations were found between single values of active, inactive or trypsin-activated renin and the corresponding levels of endogenous anti-tryptic activity. However, a weak but significant correlation (r = 0.39, P < 0.05) was found between single values of anti-tryptic activity and the corresponding percentage of activation of inactive renin.

6. Thus the maximum activation of inactive renin at 4°C for 2 min is obtained with trypsin at 2000 μg/ml independently of the corresponding endogenous anti-tryptic activity. It is not excluded that the content of protease inhibitors in human plasma might affect the proportion in vivo of circulating active and inactive renin.
Derivation of Neutral Antihypertensive Lipid from Renal Venous Effluent in Rats
Authors: Muirhead E. E. , Byers L. W. , Pitcock J. A. , Desiderio D. M. , Brooks B. , Brown Peggy , Brosius W. L.
Published: August 2015

1. The antihypertensive neutral renomedullary lipid (ANRL) is a natural product derived from fresh renal medulla and from venous blood.

2. ANRL appears to be an antihypertensive hormone secreted when the kidney exerts its antihypertensive function after unclipping.

3. The kidney appears to be the main source of ANRL, maintaining a basal rate of secretion of ANRL.

4. The kidney of the one-kidney, one-clip hypertensive rat appears to secrete an inappropriate amount of ANRL. Thus a deficiency of the secretion of the antihypertensive hormone may play a role in the pathogenesis of the one-kidney, one-clip hypertensive model.

5. Degranulation of the renomedullary interstitial cells (RIC) occurs as the kidney exerts its antihypertensive action after unclipping, supporting these cells as the source of ANRL.

6. Channels between collecting duct cells may encourage water reabsorption while the clip is in place; conversely, the closure of these channels when the clip is removed may encourage the diuresis that is observed.
Influence of Family History of Hypertension on the Relationships between Blood Pressure, Body Weight, Electrolyte Metabolism, Renin, Prolactin and Parathormone
Authors: Wessels F. , Hoffmann D. , Wagner H. , Zumkley H.
Published: August 2015

1. The influence of family history of hypertension on the relationships between blood pressure, relative body weight, sodium/creatinine ratio of the 24 h urine, plasma renin activity and the plasma concentration of prolactin and parathormone were examined in 102 healthy male students.

2. Grouping together results from all students showed significant positive correlations between systolic blood pressure and prolactin, parathormone as well as relative body weight, between plasma renin activity and prolactin and a significant negative correlation between plasma renin activity and sodium/creatinine ratio of the 24 h urine.

3. By dividing the students into two groups according to their family history of hypertension we could demonstrate in those with family history of hypertension a highly significant positive correlation between mean blood pressure and sodium/creatinine ratio of the 24 h urine and an improvement of the correlations between systolic blood pressure and prolactin and between sodium/creatinine ratio of the 24 h urine and plasma renin activity. In students without family history of hypertension these relationships were no longer detectable. In the students without family history of hypertension the correlations between systolic blood pressure and relative body weight as well as between plasma renin activity and prolactin gained substantially in significance. In students with positive family history of hypertension these correlations could no longer be demonstrated. The correlations between systolic blood pressure and parathormone remained unaffected by family history of hypertension.

4. The results suggest that a genetic predisposition to essential hypertension is able to intensify the blood pressure effect of Na intake and of prolactin, which, besides its function as a sex hormone, is presumed additionally to be able to retain salt. However, the positive relationship between body weight and blood pressure, as well as between plasma renin activity and prolactin, the significance of which increases greatly in subjects without family history of hypertension, appears to be lost as the result of the increased sensitivity to salt in positive family history of hypertension.
Hypertension in the Elderly: Haemodynamic, Fluid Volume and Endocrine Findings
Authors: Messerli F. H. , Glade L. B. , Dreslinski G. R. , Dunn F. G. , Reisin E. , MacPhee A. A. , Frohlich E. D.
Published: August 2015

1. Systemic and renal haemodynamics, intravascular volume, circulating catecholamines and plasma renin activity were measured in 18 patients with established essential hypertension who were older than 60 years of age. Each patient was matched with respect to mean arterial pressure, body surface area, race and sex with a patient that was younger than 42 years of age.

2. When compared with the younger group, elderly patients had a lower cardiac output, impaired myocardial reserve, lesser aortic elasticity, higher total peripheral resistance, more contracted intravascular volume and higher circulating noradrenaline levels.

3. Similar effects of age, although less pronounced, have been reported in normotensive subjects. We conclude that essential hypertension is a pathophysiological process that seems to accelerate the natural physiological haemodynamic, fluid volume and endocrine processes of aging.
Percutaneous Transluminal Dilatation or Surgery in the Management of Renal Vascular Hypertension?
Authors: Grim C. E. , Yune H. Y. , Weinberger M. H. , Donohue J. P.
Published: August 2015

1. Twelve patients with renal artery stenosis due to fibromuscular disease (FMD) were treated with percutaneous transluminal dilation (PTD) and their results (first year) compared with those for 26 patients treated with attempted renal artery bypass. The cumulative probability of cure at 1 year was 0.67 for PTD and 0.36 for surgery (P = N.S.) in patients with FMD. The cumulative probability of being improved or cured was 0.92 for PTD and 0.88 for surgery.

2. Eighteen patients with renal artery stenosis due to atherosclerosis were treated with PTD and their results compared with those of 28 patients treated by surgery. The cumulative probability of cure at 1 year was 0.11 for PTD and 0.17 for surgery (P = N.S.). The cumulative probability for cure or improvement at 1 year was 0.30 for PTD and 0.88 for surgery (P < 0.001).

3. We conclude that PTD may be a satisfactory alternative to surgery in fibromuscular disease, but is inferior to surgery in atherosclerotic disease causing renal artery stenosis.

4. A randomized clinical trial is needed to define the role of PTD and surgery in renal artery stenosis.
Can Placebo Therapy Influence Arterial Blood Pressure?
Authors: Gould B. A. , Mann S. , Davies A. B. , Altman D. G. , Raftery E. B.
Published: August 2015

1. With standard sphygmomanometric techniques used in conjunction with continuous intra-arterial monitoring the antihypertensive effect of placebo was examined in a group of patients participating in a controlled clinical trial.

2. Twelve of the 20 patients entered completed all stages of a randomized double-blind controlled trial of placebo and indoramin. Clinic blood pressure in patients receiving placebo showed reductions which were highly significant (P < 0.001). Simultaneous intra-arterial monitoring showed no reduction of the blood pressure over the 24 h studied.

3. The clinic pressures showed minimal reduction of blood pressure in response to indoramin therapy whereas intra-arterial pressures showed a significant fall (P < 0.01).

4. The response of the blood pressure to placebo appears to be an artifact of the indirect sphygmomanometric method and its use as a control in this study led to under-estimation of the efficacy of indoramin.
The Purine Nucleotide Profile in Mouse, Chicken and Human Dystrophic Muscle: An Abnormal Ratio of Inosine plus Adenine Nucleotides to Guanine Nucleotides
Authors: Shuttlewood R. J. , Griffiths J. R.
Published: August 2015

1. AMP, ADP, ATP, IMP, GDP, GTP and adenylosuccinate have been measured by high pressure liquid chromatography in three types of animal muscular dystrophy and in a human patient with Duchenne muscular dystrophy.

2. Abnormalities in nucleotide content varied from one dystrophy to another.

3. In each case, however, the ratio [total adenine nucleotide + IMP]/[total guanine nuclotides] was lower in dystrophic muscle, even when severely exercised or ischaemic muscles were used.

4. The practical advantages of this assay for diagnosis of muscular dystrophy are discussed.
Efflux of Noradrenaline from Platelets in Normotensive Members of Hypertensive Families
Authors: Mattiasson Ingrid , Hood B.
Published: August 2015

1. Platelets have been used as a model of sympathetic neurons to study the storage of noradrenaline in normotensive individuals belonging to families with essential hypertension for at least two generations.

2. The initial efflux rate (k) of noradrenaline was determined in 44 young relatives (mean age 29.2 years), in 18 middle-aged relatives (mean age 46.7 years) and in 31 young controls with no known family history of essential hypertension (mean age 29.8 years). From the groups of relatives all those with definite hypertension had been excluded a priori.

3. k was significantly higher in the young relatives (22.7 ± 7.9) than in the middle-aged relatives (17.7 ± 6.4) and in the controls (15.6 ± 5.1). Of the relatives 27.3% had higher k values than any of the controls. A significant correlation was found between k and diastolic blood pressure in controls but not in young relatives.
Protection of Prostacyclin-Like Activity in Human Plasma—A Non-Enzymatic Mechanism?
Authors: Mikhailidis D. P. , Mikhailidis A. M. , Woollard M. L. , Dandona P.
Published: August 2015

1. The rate of decay of the platelet anti-aggregatory activity of prostacyclin in plasma and buffer solutions was investigated.

2. Platelet anti-aggregatory activity of prostacyclin was more stable in plasma than in buffer solutions at physiological pH.

3. The rate of decay of this activity increased with an increase in incubation temperature.

4. Preheating of plasma at 65 °C led to a marked but not total loss of its ability to ‘protect’ prostacyclin.

5. Incubation of 6-keto-prostaglandin F1α in plasma did not result in the appearance of platelet anti-aggregatory activity; nor did the decay curves of prostacyclin activity indicate the emergence of any new platelet anti-aggregatory activity.

6. Incubation of 6-keto-prostaglandin E1 in plasma did not lead to any loss of its platelet anti-aggregatory activity for prolonged periods.

7. We conclude that the marked prolongation of platelet anti-aggregatory activity of prostacyclin in plasma is not due to its enzymatic conversion into 6-keto-prostaglandin E1 but due to ‘protection’ of prostacyclin itself. This ‘protection’ is probably due to an interaction with a plasma protein.
Effect of Inhibition of Prostaglandin Synthesis on Urinary Free Dopamine Excretion in Women
Authors: Güllner H.-G. , Lakatua D. J. , Bartter F. C.
Published: August 2015

1. The effect of inhibition of prostaglandin synthesis on urinary excretion of free dopamine, a catecholamine thought to act as a renal natriuretic hormone, was examined in six normal women.

2. The volunteer subjects were treated with indomethacin (2 mg day−1 kg−1) for 7 days. This regimen produced an immediate and significant but transient decrease in urinary sodium excretion, averaging about 80 mmol over a period of 3 days.

3. Urinary dopamine excretion during the control period was not different from that during the entire period of indomethacin treatment.

4. It is concluded that indomethacin does not affect urinary dopamine excretion. The change in intrarenal nervous release of dopamine in response to the sodium retention induced by indomethacin may have been too small to make a significant contribution to total urinary dopamine excretion.
Calcium Balance in Osteoporotic Patients on Long-Term Oral Calcium Therapy with and without Sex Hormones
Authors: Thalassinos N. C. , Gutteridge D. H. , Joplin G. F. , Fraser T. R.
Published: August 2015

1. The effect of a high calcium intake (1 mmol day−1 kg−1) alone or with the concomitant administration of oestradiol and testosterone derivatives was monitored by serial calcium balances in 48 patients with osteoporosis of various types.

2. On high calcium alone there was an increase (P < 0.001) in both total calcium balance and net calcium absorption as compared with values on a simulated home intake. This effect was sustained for periods up to 10 years (mean 3.5 years) by the addition of the hormones.

3. Discontinuation of the hormones (only) produced a significant decrease in both calcium balance and nett absorption but both were still increased when compared with the initial values under simulated home calcium intake.

4. No significant change in the urinary calcium output was observed under any of the regimens.
Effects of (+)-Octanoylcarnitine on Deoxyribonucleic Acid Synthesis in Regenerating Rabbit Liver
Authors: Nakatani Toshio , Yasuda Kazuhiro , Ozawa Kazue , Kawashima Sadao , Tobe Takayoshi
Published: August 2015

1. (+)-Octanoylcarnitine, a potent inhibitor of fatty acid oxidation, was infused intraportally into rabbits after 70% hepatectomy, and its effects on the rate of deoxyribonucleic acid (DNA) synthesis were examined.

2. The rate of DNA synthesis was markedly enhanced 48 h after hepatectomy. At this time, synthesis was decreased significantly by (+)-octanoylcarnitine.

3. It is suggested that fatty acid oxidation contributes to enhanced hepatic regeneration by elevating the decreased energy charge level [(ATP + 0.5ADP)/(ATP + ADP + AMP)] of the remnant liver.
Direct Radioimmunoassay of Rat Angiotensinogen and Its Application to Rats in Various Endocrine States
Authors: Bouhnik J. , Clauser E. , Gardes J. , Corvol P. , Menard J.
Published: August 2015

1. Antibodies were raised in rabbits against pure rat angiotensinogen. The antisera obtained were highly specific for rat angiotensinogen and did not bind hog, dog, rabbit, monkey or human angiotensinogen. They did not cross-react with angiotensin I, angiotensin II or synthetic hog tetradecapeptide renin substrate. However, rat des-angiotensin I—angiotensinogen cross-reacted 100% with the angiotensinogen antibody.

2. A direct radioimmunoassay for rat angiotensinogen in plasma was developed and this enabled 5 fmol of this protein to be detected. Comparison of the amounts of angiotensinogen determined by the indirect and direct assay systems indicated a 1:1.2 ratio for normal rats and rats in various endocrine states, except for adrenalectomized animals. In the latter, the angiotensinogen level measured by direct radioimmunoassay was four times that obtained by indirect assay.

3. The presence of a large amount of des-angiotensin I—angiotensinogen in adrenalectomized rat plasma is discussed.
The Contribution of the Accelerating Phase of Inspiratory Flow to Resistive Load Detection in Man
Authors: Narbed P. G. , Marcer D. , Howell J. B. L.
Published: August 2015

1. By the use of Signal Detection Theory techniques resistive load detection sensitivity was estimated in ten normal subjects during loading of the whole of inspiration and compared with loading restricted to the initial, accelerating phase of inspiratory air flow.

2. Detection sensitivity during the accelerating-flow phase of inspiration was not significantly different from that in the control conditions.

3. These results suggest that the information for detection is generated in the accelerating phase of inspiratory air flow.

4. We propose that the stimulus for resistive load detection is the ratio of the rate of change of pressure to the rate of change of flow.
Reversible Resistance to the Renal Action of Parathyroid Hormone in Human Vitamin D Deficiency
Authors: Lewin I. G. , Papapoulos S. E. , Hendy G. N. , Tomlinson S. , O'riordan J. L. H.
Published: August 2015

1. The response to exogenous parathyroid hormone (PTH) was tested in normal subjects and patients with osteomalacia due to vitamin D deficiency; 200 MRC units of bovine PTH were administered intravenously.

2. The rise in plasma adenosine 3′:5′-cyclic monophosphate (cyclic AMP) and the increase in urinary excretion of cyclic AMP were reduced in the patients with vitamin D deficiency. After treatment with vitamin D the responses returned to normal.

3. It is suggested that this reversible resistance is due to the secondary hyperparathyroidism associated with vitamin D deficiency.
Iron and Isoferritins in Iron Overload
Authors: Wagstaff M. , Worwood M. , Jacobs A.
Published: August 2015

1. The ferritin content of iron-overloaded tissues was higher than that of normal tissues. There was also an increased iron content of ferritin extracted from these tissues.

2. In the limited number of tissues that we examined haemosiderin deposition appeared to be greater in the iron-overloaded livers than in the iron-overloaded spleens.

3. Ferritins extracted from iron-overloaded liver, spleen and kidney had similar properties to those extracted from the corresponding normal tissues.

4. Ferritin from iron-overloaded heart had a greater proportion of more basic isoferritins than had ferritin from normal heart.

5. Immunoreactivity to heart and spleen ferritin antibodies, subunit composition, iron content and rate of iron uptake of both unfractionated ferritin and isoferritin fractions separated by ion exchange chromatography were related to the isoelectric point.
Measurement of Cerebral Blood Flow and Metabolism in Man
Authors: Lassen N. A.
Published: August 2015

The brain has a high blood now to meet its high obligatory requirement for glucose as a metabolic fuel. Indeed, glucose requirement and blood flow are directly coupled so that the increased metabolic rate during enhanced functional activity of a particular cortical area is associated with increased blood flow. Here a brief review will be given of the most important methods that can be used for the study of cerebral blood flow in human subjects.
Baroreflex Sensitivity during the Development of Spontaneous Hypertension in Rats
Authors: Struyker-Boudier H. A. J. , Evenwel R. T. , Smits J. F. M. , Van Essen H.
Published: August 2015

1. Baroreflex sensitivity was studied in relation to the development of spontaneous hypertension in rats (SH rats), with normotensive Wistar-Kyoto (WKY) rats as controls. Conscious, freely moving animals were studied at different times, ranging from 4 to 20 weeks after birth.

2. The youngest SH rats (4–6 weeks; n = 10) already had significantly (P < 0.01) higher mean arterial blood pressure (112 ± 2 mmHg) than WKY rats of corresponding age (95 ± 4 mmHg; n = 10). Baroreflex sensitivity did not differ at this age (0.37 ± 0.04 vs 0.38 ± 0.05 ms/mmHg).

3. Mean arterial pressure increased rapidly in SH rats during further development, reaching a value of 166 ± 3 mmHg in 12–20 week old animals (n = 25). In equally old WKY rats blood pressure was significantly (P<0.001) lower (110 ± 6 mmHg, n = 25). Baroreflex sensitivity did not change during development of SH rats (0.40 ± 0.03 ms/mmHg in 12–20 weeks old SH rats), whereas it increased two- to three-fold in WKY rats (0.93 ± 0.08 ms/mmHg, P<0.001).

4. It is concluded that an increase in baroreflex sensitivity is part of the development of a normotensive cardiovascular system, whereas in SH rats responsiveness of the baroreceptor reflex remains depressed during the development and stabilization of hypertension.
Response of Forearm Resistance Vessels to Verapamil and Sodium Nitroprusside in Normotensive and Hypertensive Men: Evidence for a Functional Abnormality of Vascular Smooth Muscle in Primary Hypertension
Authors: Robinson B. F. , Dobbs R. J. , Bayley S.
Published: August 2015

1. The response of the forearm resistance vessels to local intra-arterial infusion of verapamil and sodium nitroprusside has been assessed by a plethysmographic method in 23 men with normal arterial pressure and 35 men with primary hypertension.

2. In the 20 patients with hypertension for whom full dose—response curves were determined, the dilator response to verapamil was significantly greater than that in the normal controls, whereas the response to sodium nitroprusside was reduced.

3. Comparison of responses to the two dilators in individual subjects enabled the scattering effect of variables common to both drugs to be reduced. Analysis of the results in this way showed a highly significant difference between the hypertensive men as a whole and the normotensive controls (P < 0.00001); 24 out of the 35 hypertensive men showed responses that were outside the normal range.

4. The abnormal pattern of response observed in the hypertensive group cannot be accounted for by structural changes in the vessels and strongly suggests a functional abnormality of the vascular smooth muscle.
Plasma Renin in Long-Term Diuretic Treatment of Hypertension: Effect of Discontinuation and Restarting Therapy
Authors: Swart S. , Bing R. F. , Swales J. D. , Thurston H.
Published: August 2015

1. Plasma renin activity, body weight and blood pressure were measured before and after 7 days' treatment with bendrofluazide in ten hypertensive subjects. They were then treated with bendrofluazide alone (5 mg daily) for a minimum of 3 years. The diuretic was then discontinued and the measurements were repeated before and again after 7 days with bendrofluazide. The results were compared with those obtained before chronic treatment with the diuretic.

2. Chronic diuretic treatment was associated with a persistent and progressive rise in plasma renin activity, that fell promptly to pretreatment levels when diuretics were discontinued. This was associated with significant weight gain but no immediate significant rise in blood pressure.

3. When acutely challenged with bendrofluazide the patients showed a greater increase in plasma renin activity on the second occasion than on the first. Three out of five patients with an initially subnormal response had normal responses after chronic diuretic treatment.

4. Chronic diuretic treatment increased the responsiveness of the juxtaglomerular apparatus in some hypertensive patients.

5. Classification of hypertensive patients into renin subgroups may be influenced by previous therapy, even when that therapy has been discontinued for 4 weeks. In particular ‘low renin hypertension’ may be masked by recent use of diuretics, as shown by three of the five patients in this subgroup in the present study.