bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II Blockade in Normal Subjects and Essential Hypertensive Patients
Authors: MacGregor G. A. , Dawes P. M.
Published: August 2015

1. Saralasin (Sar1-Ala8-angiotensin II), a competitive inhibitor of angiotensin II (AII), has been infused into normal subjects and patients with essential hypertension when deprived of sodium by 5 days of a 10 mmol/day sodium diet.

2. When saralasin was given by an incremental rate of infusion starting at 0·25 μg min—1 kg—1, sodium-deprived normal subjects showed a fall in standing blood pressure with no change in lying blood pressure, sodium-deprived normal-renin hypertensive patients showed no change in lying or standing blood pressure and sodium-deprived low-renin patients showed a significant sustained rise in lying and standing blood pressure.

3. These findings suggest that: (a) standing blood pressure in sodium-deprived normal subjects is angiotensin II dependent; (b) normal-renin hypertensive patients when sodium deprived by diet alone do not appear to be angiotensin II dependent (angiotensin II is unlikely therefore to be directly maintaining their blood pressure on their normal sodium intake); (c) the rise in blood pressure seen in low-renin hypertensive patients with saralasin may be a further way of distinguishing this group of patients.
Plasma Renin Activity, Plasma Angiotensin II and Extracellular Fluid Volume in Patients after Renal Transplantation
Authors: Horvath J. S. , Baxter C. , Furby F. , Hood V. , Johnson J. , McGrath B. , Tiller D. J.
Published: August 2015

1. Patients with cadaveric renal transplants and plasma creatinine less than 177 μmol/l who had their own kidneys removed were studied.

2. The renin—angiotensin system appeared to behave in a normal fashion in response to alterations in sodium intake and posture.

3. The renin—angiotensin system had no major role in the establishment or maintenance of hypertension.

4. Mean arterial pressure was directly related to expansion of the extracellular fluid volume.
Diazoxide-induced Stimulation of Renin Release in Renal Vein Renin Sampling
Authors: Stockigt J. R. , Higgs E. J. , Sacharias N.
Published: August 2015

1. The acute effect of diazoxide (150–300 mg, intravenously) on renal venous renin has been evaluated in forty-four patients with suspected renal hypertension.

2. In twenty-seven studies which showed no lateralization, diazoxide raised the mean peripheral renin to 175% of control (P < 0·05) but the renal vein renin ratio showed an insignificant change (1·15 to 1·21).

3. In seventeen studies which showed lateralization the increase in peripheral renin was similar, but mean renal vein renin ratio increased from 1·90 to 3·52 (P < 0·005), and the mean ratio of contralateral renal vein to peripheral renin showed no change (1·05 to 1·07), indicating persistence of contralateral suppression.

4. Diazoxide accentuates the distinction between lateralizing and non-lateralizing renal vein renin studies.
Angiotensin II Analogues and Aldosterone Secretion in Sodium-Deficient Sheep
Authors: Blair-West J. R. , Coghlan J. P. , Denton D. A. , Niall H. D. , Scoggins B. A. , Tregear G. W.
Published: August 2015

1. The angiotensin analogues Sar1-Ala8-angiotensin II (AII), Sar1-Ile8-AII, Sar1-Leu8-AII, Sar1-Thr8-AII, [Des1-Asp]-Ile8-AII and [Des1-Asp]-Sar2-Ile8-AII and converting enzyme inhibitor (SQ 80221) infused by intra-adrenal arterial infusion had no effect on aldosterone secretion in sodium-deficient sheep at doses in excess of those shown to block exogenous angiotensin II or III infusion.

2. It is suggested that the intrinsic agonist activity of the analogues may fulfil the requirements for a permissive role for angiotensin in the aldosterone response to sodium deficiency.
Factors Influencing the Carotid Baroreceptor Response to Pressure Changes in a Neck Chamber
Authors: Ludbrook J. , Mancia G. , Ferrari A. , Zanchetti A.
Published: August 2015

1. Transmission of pneumatic pressure from a neck chamber to the region of the carotid sinus is imperfect and asymmetric (86% of positive pressure, 64% of negative pressure). This has to be taken into account in the correct analysis of the carotid baroreceptor reflex.

2. There is no evidence for a reduction in cerebral blood flow nor of carotid chemoreceptor stimulation in response to an increase in neck chamber pressure of about 45 mmHg. Thus it is likely that the pressor response to this manoeuvre is in fact due to reduction in carotid baroreceptor activity.
Time-Course of the Reduction of Baroreceptor Sensitivity in Experimental Hypertensive Rabbits
Authors: Angell-James Jennifer E. , George M. J.
Published: August 2015

1. Hypertension was produced experimentally in three groups of rabbits by atherosclerosis, medial sclerosis and renal encapsulation.

2. The sensitivity of afferent baroreceptor fibre recordings, obtained from an isolated perfused aortic arch preparation, was reduced in all three treated groups.

3. The reduction of baroreceptor sensitivity was directly related to the increase in the lability of the blood pressure in the intact animal and to the reduction of the distensibility of the perfused region.

4. There was a closer relationship between the length of time the rabbits had been hypertensive and the reduction in the baroreceptor sensitivity, than to the level of their blood pressure.

5. The reduction of baroreflex sensitivity obtained by the infusion of phenylephrine was also directly correlated with the period of the hypertension.

6. Baroreceptor resetting occurred to a higher pressure in the renal hypertensive group.
Cardiac Function in the Treatment of Arterial Hypertension with Propranolol
Authors: Guazzi M. , Polese A. , Fiorentini C. , Olivari M. T. , Magrini F. , Bartorelli C.
Published: August 2015

1. Propranolol, when used for treating arterial hypertension, may influence determinants of both cardiac and vascular function; the consequent changes in cardiac performance may result from the interaction of different and possibly opposite effects.

2. Cardiac function was investigated in fifty-four primary hypertensive men in the pretreatment state and after 3 weeks of propranolol therapy at a daily dose of 320 mg.

3. β-Receptor blockade caused depression of pre-injection left ventricular function, which was unrelated to the direction and the extent of changes in peripheral circulation.

4. The ejection left ventricular function could be either depressed or improved depending on the direction to which treatment shifted the vascular resistance, and consequently, the impedance to left ventricular ejection.

5. Withdrawal of the adrenergic support is probably the major factor responsible for the poor ventricular adaptation to an augmented impedance.
Prazosin and Hydrallazine in the Treatment of Hypertension
Authors: Kincaid-Smith Priscilla , Hua A. S. P. , Myers J. B. , Macdonald Ileene , Fang P.
Published: August 2015

1. Two vasodilators, prazosin and hydrallazine, have been compared in three double-blind cross-over studies designed to test their effect when used in combination with a β-adrenoceptor-blocking agent and a thiazide.

2. Single doses of 3 mg of prazosin or 75 mg of hydrallazine were administered to patients whose blood pressures remained uncontrolled on a thiazide and a β-adrenoceptor-blocking agent. Both agents produced significant falls in systolic and diastolic blood pressure apparent at 1 h. The effects of prazosin persisted for 6–7 h and those of hydrallazine for 4–6 h. Tachycardia was more marked and more prolonged after hydrallazine and continued after the blood pressure had risen to base-line levels or above.

3. In 6 week and 12 week double-blind cross-over studies, mean falls in blood pressure were similar with prazosin and hydrallazine. Similar falls in the supine diastolic blood pressure were achieved with 1 mg of prazosin and 20 mg of hydrallazine, but for a given fall in supine diastolic blood pressure, prazosin produced a significantly lower standing diastolic blood pressure.

4. Severe side effects were more pronounced after hydrallazine, which necessitated withdrawal of seven patients, whereas only one patient on prazosin withdrew from the trial because of side effects.
Increased Renal Excretion of Arginine-Vasopressin during Mild Hydropenia in Young Men with Mild Essential Benign Hypertension
Authors: Khokhar A. M. , Slater J. D. H.
Published: August 2015

1. The rate of renal excretion of arginine-vasopressin was determined during unrestricted fluid intake for 24 h and in response to fluid deprivation for 18 h in nine young men with very mild essential hypertension and compared with that in sixteen normotensive men of similar age.

2. Despite an equilavent osmolar stimulus, excretion of arginine-vasopressin was significantly greater in the hypertensive group than in the reference group. This difference increased progressively with increasing dehydration.

3. We suggest that these findings are mainly due to an increased rate of secretion of arginine-vasopressin in response to mild hydropenia in hypertensive patients and that a moderate increase of release of arginine-vasopressin during periods of fluid deprivation may exert vascular effects and thus influence the perpetuation of hypertension.
Evidence for Renal Control of Urinary Excretion of Bile Acids and Bile Acid Sulphates in the Cholestatic Syndrome
Authors: Summerfield J. A. , Cullen Julia , Barnes S. , Billing Barbara H.
Published: August 2015

1. The bile acids and bile acid sulphates in the urine, serum and bile of eight cholestatic patients were studied quantitatively by gas-liquid chromatography and gas-liquid chromatography/mass spectrometry.

2. The primary bile acids (cholic acid and chenodeoxycholic acid) comprised on average 94% of the total bile acids in bile, 70% in the serum and 64% in urine.

3. The percentage composition of bile acids in bile was relatively constant and was not influenced by the degree of cholestasis. In contrast, in the serum only the primary bile acids were increased, the concentrations of the secondary bile acids (deoxycholic acid and lithocholic acid) and the minor bile acids remaining constant.

4. The data do not support the hypothesis that monohydroxy bile acids accumulate in cholestasis and are related to the pathogenesis of this syndrome.

5. The pattern of bile acid urinary excretion was similar to that in the serum. But in one patient, 3α,7β,12α-trihydroxy-5β-cholan-24-oic acid was a principal urinary bile acid, although very low concentrations of the compound were found in that patient's serum, suggesting that some of the minor bile acids in urine may originate by epimerization in the kidney.

6. In bile only a small proportion of the bile acids was sulphated (range 2·1–4·6%) and in serum the degree of sulphation was very variable (9–50%). However, in urine, sulphate esters accounted for a large proportion of the total bile acids (33–72%).

7. The output of bile acid sulphate in the urine was related to the urine total bile acid output but the serum concentration of bile acid sulphate remained relatively constant. Consequently, in contrast to the non-sulphated bile acids, whose renal clearance was relatively constant, the renal clearance of sulphated bile acids was directly related to the urine total bile acid output. This finding is inconsistent with the earlier hypothesis that their predominance in urine was due to a high renal clearance. It may indicate renal synthesis of some of the bile acid sulphates in the urine and/or inhibition of active renal tubular reabsorption of sulphated bile acids by non-sulphated bile acids.
Effects of Metabolic Alkalosis, Metabolic Acidosis and Uraemia on Whole-Body Intracellular pH in Man
Authors: Tizianello A. , De Ferrari G. , Gurreri G. , Acquarone N.
Published: August 2015

1. Whole-body intracellular pH (pH1) was measured by the 14C-labelled DMO method in twenty-four control subjects, eighteen normal subjects with induced acute metabolic alkalosis, ten normal subjects with induced acute metabolic acidosis, twelve normal subjects with chronic acidosis and in fifteen patients with chronic renal insufficiency and acidosis.

2. The change in pH1 per unit change in extracellular pH is significantly larger in acute metabolic alkalosis than in acute metabolic acidosis. In chronic metabolic acidosis, pH1 decreased in proportion to the total amount of ammonium chloride administered; pH1 was normal in patients with uraemic acidosis.

3. These observations confirm the role that tissue buffers play in the protection of the cellular environment in some forms of acidosis. When the acid load overwhelms tissue buffer capacity, pH1 becomes a function of extracellular pH.

4. Cells seem more protected from acute acidosis than from acute alkalosis.
Resolution of Hypoxic Changes in the Heart and Pulmonary Arterioles of Rats during Intermittent Correction of Hypoxia
Authors: Leach Enid , Howard P. , Gwenda R. Barer
Published: August 2015

1. Rats kept in a hypoxic chamber (10% O2) for 3 or more weeks developed right ventricular hypertrophy, muscularization of pulmonary arterioles and polycythaemia. These changes resemble those found in human hypoxic disease and, in particular, in patients dying from chronic airways obstruction.

2. Resolution of these changes was studied in a normal environment and in an intermittently normal, intermittently hypoxic environment. The latter regimen modelled the situation of patients with cor pulmonale receiving long-term intermittent oxygen therapy.

3. In a normal environment right ventricular hypertrophy and polycythaemia were resolved in 6 weeks but vessel changes were not resolved in 12 weeks.

4. In the intermittently normoxic environment (40 or 80 h in air per week) there was some resolution of right ventricular hypertrophy in 6 weeks but no significant reduction in vessel thickening or in polycythaemia in 12 weeks.
Enzyme Activities in Human Liver Biopsies: Assay Methods and Activities of Some Lysosomal and Membrane-Bound Enzymes in Control Tissue and Serum
Authors: Seymour Carol A. , Peters T. J.
Published: August 2015

1. Highly sensitive techniques are described for the assay of plasma membrane (5′-nucleotidase, alkaline phosphatase), microsomal (neutral α-glucosidase, leucyl-2-naphthylamidase) and biliary canalicular (γ-glutamyltransferase) enzymes and for nine acid hydrolases (acid phosphatase, phosphodiesterase, β-glucosidase, α-glucosidase, α-galactosidase, β-galactosidase, α-mannosidase, N-acetyl-β-glucosaminidase, β-glucuronidase) in human liver.

2. Optimum and specific assay systems have been developed which give linear kinetics for all enzymes.

3. The range of enzyme activities in samples of human liver, obtained by closed needle biopsy, and in sera have been determined.
Factors affecting angiotensin II concentrations in the human infant at birth
Authors: Pipkin Fiona Broughton , Symonds E. M.
Published: August 2015

1. A radioimmunoassay for the measurement of angiotensin II in 1 ml of plasma has been developed and used to measure angiotensin II in maternal peripheral, cord venous and cord arterial blood in 45 patients at delivery.

2. In babies delivered vaginally, cord venous and cord arterial concentrations of angiotensin II were significantly higher than maternal venous blood concentrations. There was a significant relationship between both cord venous and cord arterial concentrations and maternal concentrations of angiotensin II.

3. Cord venous concentrations of angiotensin II were significantly greater than those in cord arterial blood in babies delivered vaginally but not in those delivered by lower-segment Caesarean section. This suggests the possibility that, during labour, the placenta may contribute to foetal concentrations of angiotensin II.

4. Maternal and cord venous concentrations of angiotensin II were significantly higher in patients with hypertensive disease of pregnancy than in those who had remained normotensive throughout pregnancy.

5. Cord venous concentrations of angiotensin II increased significantly with increasing duration of the second stage of labour.
Intrarenal Distribution of Plasma Flow in Cirrhosis as Measured by Transit Renography: Relationship with Plasma Renin Activity, and Sodium and Water Excretion
Authors: Wilkinson S. P. , Smith I. K. , Clarke M. , Arroyo V. , Richardson J. , Moodie H. , Williams R.
Published: August 2015

1. The intrarenal distribution of plasma flow was determined with a technique based on the analysis of the transit time of sodium o-[131I]-iodohippurate through the kidney in 43 patients with cirrhosis with near-normal total renal perfusion.

2. Twenty-five of the patients had an abnormal pattern of transit times, suggesting a redistribution of plasma flow from outer cortical to juxtamedullary nephrons.

3. Plasma renin activity ranged from below normal to six times normal and high values were found only in patients showing an abnormal pattern of transit times. The latter was also found to be related to sodium retention and a reduced renal capacity to excrete free water.
Protein Metabolism in Human Neonates: Nitrogen-Balance Studies, Estimated Obligatory Losses of Nitrogen and Whole-Body Turnover of Nitrogen
Authors: Pencharz P. B. , Steffee W. P. , Cochran W. , Scrimshaw N. S. , Rand W. M. , Young V. R.
Published: August 2015

1. Aspects of nitrogen metabolism in the human neonate were assessed in one full-term infant and six premature infants by means of nitrogen-balance measurements, estimates of obligatory nitrogen losses and determinations of whole-body nitrogen turnover.

2. Our data indicate that the mean protein requirement for maintenance is 1·1 g of protein day−1 kg−1 and that 3·8 g of protein day−1 kg−1 should be sufficient for adequate growth in healthy premature babies.

3. The mean obligatory urinary, faecal and total nitrogen losses were estimated to be 24, 106 and 145 mg day−1 kg−1 respectively. These figures are compared with published values for older infants, and the possible metabolic basis for changes in nitrogen losses during growth and development is discussed.

4. Mean values for whole-body protein synthesis and breakdown were 26·3 ± 7·0 and 23·8 ± 7·4 g of protein day−1 kg−1 respectively. Dietary nitrogen intake accounted for 6–18% of the nitrogen flux through the metabolic pool; urea excretion accounted for 2% of the nitrogen flux.

5. The net protein gain, estimated from nitrogen-balance data, accounted for 9·6% of total daily protein synthesis.

6. These results are discussed in relation to published estimates of whole-body protein synthesis and breakdown at various ages. Their possible significance in the assessment of a ‘maintenance’ requirement for protein and amino acids during the period of rapid growth and development is also considered.
Prostaglandin Activity in Sustained Inflammation of Human Skin before and after Aspirin
Authors: Plummer N. A. , Hensby C. N. , Black A. Kobza , Greaves M. W.
Published: August 2015

1. Pharmacologically active mediators of inflammation were obtained from suction bullae raised on normal and inflamed human abdominal skin. These contained a clear inflammatory exudate, which was analysed for known mediators of inflammation.

2. The exudates were examined for smooth muscle-contracting activity by a superfusion cascade bioassay, for prostaglandin F2α by radioimmunoassay and by Lipidex 5000 gel-partition chromatography for other prostaglandins and related compounds.

3. Tetrahydrofurfuryl nicotinate (Trafuril) was applied topically before and after systemic administration of aspirin. Trafuril alone caused a sustained inflammatory response within minutes of application, which was reduced by prior administration of aspirin (a known prostaglandin synthetase inhibitor).

4. Exudate from inflamed skin showed increased prostaglandin activity compared with exudate from contralateral non-inflamed skin. However, aspirin prevented this increase in prostaglandin activity. Analysis by thin-layer and gas—liquid chromatography further suggested that Trafuril-induced inflammation was mediated by certain prostaglandins and related compounds.

5. No evidence was obtained to suggest any change in histamine or bradykinin after Trafuril. We suggest that the response caused by Trafuril is mediated by increased synthesis of prostaglandins. Aspirin, by blocking prostaglandin synthesis, prevents or reduces the erythema.
Effect of Warfarin on the Metabolism of Phylloquinone (Vitamin K1): Dose—Response Relationships in Man
Authors: Shearer M. J. , McBurney A. , Breckenridge A. M. , Barkhan P.
Published: August 2015

1. The dose—response relationship between the oral anticoagulant, warfarin, and its effect on the metabolism of phylloquinone (vitamin K1) has been examined in normal male volunteer subjects.

2. In each study the subject received a single, oral dose of warfarin and, 2 h later, an intravenous injection of [1′,2′-3H2]phylloquinone. Changes in the metabolism of phylloquinone were assessed by the fractionation and chromatographic separation of labelled phylloquinone and its metabolites in plasma and urine samples.

3. Increasing doses of warfarin did not affect the rate of disappearance of injected phylloquinone from the plasma but caused the accumulation of increasing amounts of the metabolite, phylloquinone epoxide.

4. Increasing doses of warfarin were found to decrease the proportion of labelled conjugates excreted in the urine as glucuronides and to block progressively the excretion of the normal aglycones of phylloquinone. At the same time there was a progressive increase in the excretion of at least three abnormal aglycones of phylloquinone.

5. The doses or plasma concentrations of warfarin were related to the increase in phylloquinone epoxide in the plasma and to the decrease in the proportion of normal aglycones of phylloquinone in urine by typical log dose—response curves, which were linear over the therapeutic range.

6. The nature of the metabolites detected suggested that the dose—response curves reflected the progressive inhibition by warfarin of the enzyme, phylloquinone epoxide reductase.

7. The results are consistent with the hypothesis that the pharmacological action of oral anticoagulants is closely linked to their ability to inhibit the cyclic interconversion of vitamin K and vitamin K epoxide.
Renal Handling of Dibasic Amino Acids and Cystine in Cystinuria
Authors: Kato Tomoaki
Published: August 2015

1. The effect of intravenous infusion of l-lysine and l-arginine on the tubular reabsorption of dibasic amino acids and cystine was studied in normal individuals and in homozygous and heterozygous subjects with cystinuria.

2. The control subjects reabsorbed almost all filtered lysine and arginine until the filtered load was elevated about fourfold. With further increased loads the tubular reabsorption began to fall and tended to approach a maximum reabsorption rate. By contrast, the homozygous subjects could not reabsorb the elevated amino acid beyond the endogenous capacity until the filtered load was increased seven- to ten-fold. When the filtered load was further increased, tubular reabsorption proceeded at the normal rate in the cystinuric patients.

3. These findings may be explained by a low-capacity transport system, which acts at low substrate concentrations, being defective in the cystinuric subjects, while a high-capacity transport system, which predominates at high substrate concentrations, remains intact.

4. Lysine and arginine infusion depressed the percentage tubular reabsorption of other dibasic amino acids and cystine both in the control and the cystinuric subjects. In the control subjects the amino acid infusion caused a gradual linear fall in the fractional reabsorption of the dibasic amino acids and cystine, whereas the depressed reabsorption of the dibasic amino acids in the cystinuric patients returned to that observed under the endogenous condition when the filtered load was high. The amino acid load caused only a gradual decrease in cystine reabsorption in the cystinuric patients.

5. In the heterozygous subjects the slope of the titration curves and the depression of the tubular reabsorption were intermediate between those of the control and homozygous subjects.
The Variable-Pressure Neck-Chamber Method for Studying the Carotid Baroreflex in Man
Authors: Ludbrook J. , Mancia G. , Ferrari A. , Zanchetti A.
Published: August 2015

1. The variable-pressure neck-chamber method was analysed in ten healthy volunteer subjects to determine its suitability for the study of the carotid baroreceptor reflex in man.

2. Positive and negative pressures applied to the neck (range ± 60 mmHg) were always transmitted linearly to a tissue catheter outside the carotid sinus, but only 86% of positive pressure, and 64% of negative pressure. Tissue pressures were confirmed by simultaneous measurement in the internal jugular vein adjacent to the carotid sinus.

3. Positive and negative pressure changes within the above range did not alter Po2 of internal jugular venous blood, suggesting that cerebral blood flow was unaltered.

4. Positive pressure changes induced reflex pressor responses of similar magnitude at arterial Po2 12·8 and 70·1 kPa (96 and 527 mmHg), suggesting that the carotid chemoreceptors were not involved.

5. It is concluded that the variable-pressure neck chamber is a valid method for selectively studying the carotid baroreceptor reflex in man. However, transmission of external pneumatic pressure to the carotid sinus is imperfect and greater for positive than for negative pressure. This must be recognized to avoid underestimation of gain and distortion of shape of the reflex.
Control of Renal Tubular Phosphate Reabsorption by Parathyroid Hormone in Man
Authors: Walker D. A. , Davies S. Joyce , Siddle K. , Woodhead J. S.
Published: August 2015

1. The maximum tubular reabsorption capacity for phosphate relative to glomerular filtration rate (Tm,P/GFR) was found to range from 0·8 to 1·5 mmol/l in 32 normal fasting subjects. In 14 patients with primary hyperparathyroidism and five patients with hyperparathyroidism secondary to vitamin D deficiency or malabsorption values ranged from 0·2 to 0·8 mmol/l.

2. Plasma parathyroid hormone concentrations measured by an immunoradiometric technique ranged from <0·15 to 0·9 ng/ml in the normal subjects and from 0·5 to 10 ng/ml in the patients with hyperparathyroidism. There was no correlation, however, between plasma parathyroid hormone and Tm,P/GFR in either normal or abnormal groups.

3. Plasma parathyroid hormone was lower in 11 out of 13 patients with primary hyperparathyroidism 3 or 4 weeks after tumour removal than immediately before the operation. In all cases there was a rise in Tm,P/GFR, though not all values were normalized.

4. Changes in plasma parathyroid hormone, Tm,P/GFR and plasma and urinary cyclic AMP concentrations were measured during infusion of bovine parathyroid hormone into normal fasting subjects. Phosphate reabsorption fell markedly in response to low doses of parathyroid hormone (0·5 i.u. h−1 kg−1), higher doses (4 i.u. h−1 kg−1) producing little additional change in Tm,P/GFR despite large changes in cyclic AMP excretion. At the highest doses used (8 i.u. h−1 kg−1) apparent saturation of the renal adenylate cyclase occurred. During an infusion of hormone, 0·25 i.u. h−1 kg−1 over 3 h, a fall in Tm,P/GFR was recorded at concentrations of immunoreactive parathyroid hormone within the normal range for endogeneous hormone. At such concentrations it was not possible to detect significant changes in either plasma or urine cyclic AMP.

5. It is concluded that parathyroid hormone is an important regulator of renal phosphate handling under normal physiological conditions. Such a regulatory process has been implicated in the control of vitamin D metabolism.
The Effect of α-Adrenoreceptor Stimulation on the Airways of Normal and Asthmatic Man
Authors: Snashall P. D. , Boother Frances A. , Sterling G. M.
Published: August 2015

1. The bronchial response to α-adrenoreceptor stimulation has been investigated in normal and asthmatic subjects with a specific α-receptor agonist, methoxamine hydrochloride, after atropine and β-adrenergic blockade.

2. No significant changes in forced expiratory volume in 1 s (FEV1·0) were seen in normal subjects.

3. Methoxamine inhalation caused mild symptomatic wheezing and significant falls in FEV1·0 in asthmatic subjects. No change in FEV1·0 occurred after inhalation of distilled water as control.

4. It therefore appears that methoxamine causes bronchoconstriction in asthmatic subjects through its α-adrenergic-stimulating properties, since we were not able to detect any β-receptor-blocking activity of methoxamine on the airways.
Evidence of Increased Oxalate Absorption in Patients with Calcium-Containing Renal Stones
Authors: Hodgkinson A.
Published: August 2015

1. The possible roles of the diet and of intestinal absorption in the increased excretion of oxalate by patients with renal calcium stones have been studied.

2. Dietary surveys showed that the mean daily intake of oxalic acid by stone-formers was not significantly different from that of non-stone-formers.

3. The mean urinary excretion of oxalate, expressed as an oxalate/creatinine molar ratio, was significantly reduced by fasting, the change being more marked in the stone-formers than in the normal subjects. Moreover, fasting abolished the difference in mean oxalate/creatinine ratios between stone-formers and control subjects.

4. These results are compatible with the hypothesis that the small increases in urinary oxalate excretion which occur in some idiopathic calcium oxalate stone-formers are due to increased absorption of oxalate from the intestine, which may be due to a reduction in intraluminal calcium concentration.
Lecithin—Cholesterol Acyltransferase and the Lipoprotein Abnormalities of Obstructive Jaundice
Authors: Agorastos J. , Fox C. , Harry D. S. , McIntyre N.
Published: August 2015

1. We have studied the plasma lipoprotein abnormalities in obstructive jaundice to test the hypothesis that the abnormalities would correlate with plasma lecithin—cholesterol acyltransferase activity.

2. Very-low-density lipoproteins (VLDL) were normal in composition and had a normal pre-β electrophoretic mobility when lecithin—cholesterol acyltransferase activity was high. When it was low VLDL had abnormal composition and ran in the β position.

3. With high lecithin—cholesterol acyltransferase activity, low-density lipoprotein (LDL) was normal and cholestatic LDL (LP-X) was not found. With low lecithin—cholesterol acyltransferase activity up to three LDL fractions were found: (i) large triglyceride-rich particles, (ii) LP-X and (iii) a triglyceride-rich cholesteryl ester-poor particle of normal dimensions.

4. High-density lipoprotein (HDL) concentrations correlated with lecithin—cholesterol acyltransferase activity and HDL were normal in composition and electron-microscopic appearance when the activity was high. When lecithin—cholesterol acyltransferase activity was low HDL was abnormal in composition and ‘stacked discs’ were seen on electron microscopy as well as normal spherical particles.

5. These results suggest that low lecithin—cholesterol acyltransferase activity may cause at least some of the lipoprotein changes of obstructive jaundice.
Effect of Carbamazepine on Plasma and Urine Arginine-Vasopressin
Authors: Thomas T. H. , Ball S. G. , Wales J. K. , Lee M. R.
Published: August 2015

1. Five normal subjects were studied before and during treatment with carbamazepine.

2. Plasma sodium, plasma and urine arginine-vasopressin and urine osmolality were measured during a day of water deprivation, before and during drug treatment.

3. During treatment with carbamazepine plasma sodium increased whereas plasma and urine arginine-vasopressin and urine osmolality decreased. Plasma and urine arginine-vasopressin were significantly correlated with urine osmolality. However, carbamazepine did not affect the osmolality of urine produced by the kidney, in response to endogenous arginine-vasopressin.

4. Plasma and urine arginine-vasopressin were significantly correlated with plasma sodium on both control and drug-treatment days, but the relationships of plasma and urine arginine-vasopressin to plasma sodium were different during carbamazepine treatment, as compared with the control period.

5. It is suggested that the threshold of the hypothalamic osmoreceptors for release of arginine-vasopressin is modified by carbamazepine, and that this may be either a direct action or secondary to another action of the drug.
Effect of Antitonin on Blood Pressure in the One-Kidney Hypertensive Rat
Authors: Garcia R. , Boucher R. , Gutkowska J. , Kondo K. , Demassieux S. , Genest J.
Published: August 2015

1. The tonin concentration of saliva and submaxillary glands was studied in one-clip hypertensive rats with or without the contralateral kidney.

2. Salivary tonin concentration was elevated in one-kidney hypertensive rats, but not in one-kidney normotensive or two-kidney, one-clip hypertensive rats. In contrast, an elevated submaxillary gland tonin concentration was found only in uninephrectomized animals, whether normotensive or hypertensive.

3. A single intravenous administration of rabbit tonin antiserum into one-kidney hypertensive rats restored blood pressure to normal in seven out of ten animals. There was little change in blood pressure in two-kidney, one-clip hypertensive, uninephrectomized or sham-operated rats.

4. These findings suggest a connection between the physiology of the kidney and of the submaxillary gland in the rat, and indicate that tonin may play a significant role in maintaining high blood pressure in one-kidney hypertensive animals.
Determination of Human Leg Blood Flow: A Thermodilution Technique Based on Femoral Venous Bolus Injection
Authors: Jorfeldt L. , Juhlin-Dannfelt A. , Pernow B. , Wassén E.
Published: August 2015

1. A thermodilution method was developed for the determination of human leg blood flow. The method is based on bolus injection of an indicator distally into the femoral vein, at room temperature, and recording of the dilution curve in the same vessel at the level of the inguinal ligament. The blood flow was computed automatically with two thermistors and an integrator.

2. The leg blood flow determined by this method at rest and during exercise at work loads of 50, 100 and 150 W in six healthy subjects was found to agree closely with measurements by an intraarterial indicator-dilution technique. A linear relationship was found between leg blood flow and work. The reproducibility of the blood flow determinations, expressed as the coefficient of variation for a single determination, was 12·9 at rest and 5·3 or less during exercise.

3. The method was used in two patients with occlusive arterial disease of the leg. Extremely low leg blood flows were found in these patients when they were forced to interrupt the exercise by severe calf pain.
Effect of Varying Pco2 on Intracellular pH and Lactate Consumption in the Isolated Perfused Rat Liver
Authors: Baron P. G. , Iles R. A. , Cohen R. D.
Published: August 2015

1. The effects of varying Pco2 on lactate uptake and intracellular pH (pHl) were studied in the isolated rat liver perfused with differing concentrations of lactate.

2. In general, pHl and lactate uptake are inversely related to Pco2, and pHl and lactate uptake are directly related to each other, but the quantitative aspects and significance of these relationships vary with the availability of lactate. A model of hepatic lactate metabolism is proposed which may account for the quantitative variation.

3. The metabolism of lactate within the hepatocyte exerts a destabilizing effect on hepatocyte cell pH, in contrast to the buffering effect seen in predominantly glycolytic tissues.

4. An attempt is made to relate the findings to the disturbances of lactate metabolism in clinical respiratory failure.
Mechanism of the Effect of Varying Pco2 on Gluconeogenesis from Lactate in the Perfused Rat Liver
Authors: Iles R. A. , Baron P. G. , Cohen R. D.
Published: August 2015

1. The effects of varying Pco2 on glucose output and the intracellular concentrations of lactate, pyruvate, phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate were studied in the isolated rat liver perfused with differing concentrations of lactate.

2. When the perfusate lactate concentration is above 1.5 mmol/l respiratory acidosis (simulated by high perfusate Pco2) inhibits gluconeogenesis from lactate, whereas respiratory alkalosis stimulates gluconeogenesis.

3. In general there were significant positive correlations between intracellular pH (pHl) and hepatocyte phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate concentrations, and negative correlations between pHl and lactate and pyruvate concentrations; there were usually significant correlations in the opposite sense between these metabolites and log Pco2.

4. The results suggest that CO2 exerts an inhibitory effect on gluconeogenesis at a step between pyruvate and phosphoenolpyruvate; however, this is not the only effect of CO2 on the gluconeogenic sequence. CO2 probably acts by changing pHl, but direct effects of CO2 and HCO−3 cannot be excluded.

5. Except at low lactate concentrations, non-ionic diffusion probably does not play a major role in the entry of lactate into the hepatocyte.
Partial Characterization of Aortic Renin in the Spontaneously Hypertensive Rat and its Interrelationship with Plasma Renin, Blood Pressure and Sodium Balance
Authors: Barrett J. D. , Eggena P. , Sambhi M. P.
Published: August 2015

1. A renin-like enzyme in aortic tissue of the spontaneously hypertensive rat was found to be a freely dissociable enzyme (saline homogenization) with an affinity for the renin inhibitor pepstatin. At neutral pH values, the enzyme was active in homologous plasma to produce angiotensin I, and therefore distinct from pseudorenin and cathepsin D. The arterial enzyme and semi-purified renal renin could not be distinguished on the basis of Km values by using homologous renin substrate

2. An inverse relationship between the aortic renin content of the spontaneously hypertensive rat and the progressive increase of systolic blood pressure was observed with age. In contrast to this strain of rat, aortic renin of the normotensive WKY strain did not decline with age.

3. Plasma renin concentration and the aortic renin content of the spontaneously hypertensive rat showed divergent changes in response to a blood pressure fall associated with acute diuretic therapy, chronic administration of hydrallazine and in some animals in response to chronic administration of propranolol.

4. A low sodium diet elevated both plasma and aortic renin and retarded the progressive increase of blood pressure in the spontaneously hypertensive rat. A high sodium diet accelerated the progress of hypertension with no effect on aortic or plasma renin.

5. Antihypertensive therapy (1–6 weeks), resulting in a lowering of conscious systolic blood pressure of the spontaneously hypertensive rat, consistently led to a decrease in aortic renin content.
The Tubular Reabsorption of Phosphate in Sickle-Cell Nephropathy
Authors: De Jong P. E. , Den Berg L. T. W. De Jong-Van , Van Eps L. W. Statius
Published: August 2015

1. In a series of patients with sickle-cell anaemia, serum phosphate and magnesium concentrations were elevated. Serum calcium concentrations were normal. Urinary excretion of calcium was decreased.

2. The maximum tubular reabsorption of phosphate per litre of glomerular filtrate (TmP/GFR) was significantly increased in these patients.

3. The increase in phosphate reabsorption explains the elevated serum phosphate observed in these patients.
Nervous System and Hypertension
Authors: Chalmers J. P.
Published: August 2015

1. Presynaptic regulation. The regulation of noradrenaline release by a wide variety of substances acting on presynaptic receptors suggests that local factors may play a greater role in the control of blood pressure than was previously believed and that a number of new approaches to the drug treatment of hypertension could be developed. It also raises the possibility that there might be differences in the presynaptic receptor populations of hypertensive and normotensive subjects or animals.

2. Central nerve pathways. There is a need for more precise delineation of central nerve tracts subserving a cardiovascular function and for greater use of morphological techniques to confirm the reliability of biochemical and physiological experiments in the central nervous system. Two appropriate techniques are described.

3. Models of experimental hypertension. (a) Neurogenic hypertension: interference with baroreceptor afferents can cause a permanent elevation of arterial pressure mediated by increased activity of peripheral sympathetic nerves and of descending noradrenergic nerves terminating in the spinal cord. Catecholamine nerve connections of the nucleus tractus solitarius serve mainly to modulate rather than to mediate baroreceptor reflexes. (b) DOCA—salt hypertension: increased peripheral sympathetic activity is important in both the initiation and the maintenance of this form of hypertension. The decrease in brain-stem noradrenaline turnover found in this model could play a determinant role in the development of the high blood pressure. (c) Renal hypertension: both central and peripheral nervous mechanisms contribute to the development and the early phase of ‘one-kidney’ hypertension in animals. Their role in the maintenance of this form of hypertension is still controversial. (d) Spontaneously hypertensive rats: peripheral and central mechanisms do not appear to have a major role in the maintenance of this form of hypertension. However, it seems possible that centrally evoked increases in peripheral sympathetic activity could be important in the initiation of the high blood pressure. (e) Central catecholamines and blood pressure control; central catecholaminergic nerves do not make up a single homogeneous system. For example, the activity of descending noradrenergic nerves in the spinal cord contributes to an elevation of arterial pressure, whereas the activity of catecholaminergic nerves in the dorsomedial medulla appears to have a depressor effect.

4. Human essential hypertension. (a) There is no good evidence that the nervous system plays the major primary role in the development or maintenance of essential human hypertension. (b) Effective treatment of raised blood pressure through nervous mechanisms requires an understanding of the factors that normally control the pressure and does not necessarily depend on reversing specific nervous processes responsible for producing the increase in pressure.
Albumin/Globulin Ratios, Colloid Osmotic Pressures and Lowry Protein Microanalysis in Rat Plasma
Authors: Weller D. , Azar S. , Johnson M. A. , Azar M.
Published: August 2015

1. We have correlated measurements of colloid osmotic pressure with protein concentrations and albumin/globulin ratios. Plasma from normal rats of different genetic strains was used.

2. The Landis and Pappenheimer equation does not accurately predict colloid osmotic pressure properties of the normal rat plasma used, which had an albumin/globulin ratio of 0.74. Over the range 2.2−12.2 g of protein/100 ml, the measured colloid osmotic pressures vary between −5% and +10% from the value predicted by the equation.

3. In Wistar-derived genetically hypertensive and normotensive rats, albumin/globulin ratios were higher than those in common Wistar rats. Owing to the presence of higher globulins, plasma proteins were higher in Wistar than spontaneously hypertensive and normotensive rats, and colloid osmotic pressure was identical in the three groups.

4. When common Sprague—Dawley rats were obtained from two different suppliers, their albumin/globulin ratios were found to be different.

5. As the difference in albumin/globulin ratio between human and rat plasma becomes more pronounced, predicting rat plasma colloid osmotic pressure from the Landis and Pappenheimer equation becomes less accurate. Environmental and/or genetic factors play a role in the albumin/globulin ratio found in normal healthy rats.

6. Therefore albumin/globulin ratios should be measured in each experimental situation. If the ratios are close to that of human plasma, the Landis and Pappenheimer equation can be used. If not, a new colloid osmotic pressure-protein expression should be derived.

7. Calculation of glomerular capillary pressures from directly measured colloid osmotic pressure values reduces error.
Acute Effects of Diuretics on Potassium Exchange, Mechanical Function and the Action Potential in Rabbit Myocardium
Authors: Poole-Wilson P. A. , Cobbe S. M. , Fry C. H.
Published: August 2015

1. We have studied the acute effects of frusemide, triamterene and amiloride on potassium exchange, the action potential and mechanical function of isolated rabbit myocardium.

2. Potassium exchange in the myocardium was unaltered by these diuretics.

3. Frusemide and amiloride did not affect the action potential of rabbit papillary muscles. Triamterene caused a transient shortening of the action potential.

4. Frusemide and triamterene did not alter myocardial mechanical function in rabbit papillary muscles or the interventricular septum. Amiloride caused a reduction of about 5% in developed tension in two out of three papillary muscles.
Plasma Noradrenaline and the Pressor Action of Exogenous Noradrenaline in Normotensive Subjects and Patients with Essential Hypertension
Authors: Philipp T. , Distler A. , Cordes U. , Wolff H. P.
Published: August 2015

1. An inverse relationship was found between plasma noradrenaline and reactivity to exogenous noradrenaline in normotensive subjects.

2. The relationship between plasma noradrenaline and reactivity was disturbed in age-matched patients with essential hypertension.

3. A multiple-regression analysis showed a highly significant correlation between adrenergic activity and reactivity to noradrenaline and the mean arterial blood pressure level (r = 0·91). The results suggest that adrenergic activity and pressor response to noradrenaline combined are important determinants of arterial blood pressure.

4. An inverse relationship could also be demonstrated between plasma renin activity and reactivity to exogenous angiotensin II. No difference was observed between normotensive and hypertensive subjects.
Plasma Noradrenaline, Age and Blood Pressure: A Population Study
Authors: Jones D. H. , Hamilton C. A. , Reid J. L.
Published: August 2015

1. Mean supine plasma noradrenaline was lower in 12 male laboratory staff (0·24 ± 0·02 μg/l) than similarly normotensive out-patients (0·44 ± 0·07 μg/l).

2. In 164 non-medical hospital staff, plasma noradrenaline increased with age in white males only.

3. Plasma noradrenaline was significantly higher in women than men.

4. There was no relationship between supine blood pressure and plasma noradrenaline in normotensive or hypertensive subjects.
Different Secretion Patterns of Active and Inactive Renin in Man
Authors: Kappelgaard A. M. , Giese J. , Ibsen H. , Nielsen M. Damkjær , Rabøl A.
Published: August 2015

1. In plasma samples from normal subjects and patients with untreated essential hypertension, the concentration of inactive renin (as measured after acidification) was on average 4–5 times higher than the concentration of active renin (as measured without acidification).

2. Plasma angiotensin II concentration was correlated to active renin but not to inactive renin.

3. A hyperacute stimulation induced by infusion of saralasin resulted in a marked rise of active renin, whereas inactive renin remained unchanged.

4. An acute stimulation induced by frusemide and ambulation led to a considerable rise in active renin and a slight, but significant, rise of inactive renin.

5. Stimulation with oral thiazide over 5 days induced a seven-fold rise of active renin, with a doubling of inactive renin. Thiazide treatment for 3 months led to a four-fold rise of active renin and a three-fold rise of inactive renin.

6. There was no difference between the concentrations of inactive renin in systemic plasma, ipsilateral and contralateral renal venous plasma in 12 patients with renovascular hypertension, neither before nor after infusion of saralasin with the associated fall in blood pressure.

7. We conclude that the time constants pertinent to secretion or release of active and inactive renin in man are of different orders of magnitude.