bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship between the Formation of Urea and Argininosuccinate in a Patient with Argininosuccinic Aciduria Studied with Labelled Precursors
Authors: Crane C. W. , Jenner F. A. , Pollitt R. J.
Published: August 2015

1. The time-course of urinary excretion of [15N]urea and [15N]argininosuccinate or [15N]arginine after an oral dose of [15N]ammonium lactate has been followed in patients with argininosuccinic aciduria and cystine-lysinuria respectively. The labelled argininosuccinate and arginine appeared more slowly than expected on simple precursor-product models.

2. In the patient with argininosuccinic aciduria, simultaneous ingestion of [15N]-ammonium lactate and [carbamoyl-14C]citrulline gave very different ratios of labelling with the two isotopes for urinary urea and argininosuccinate. Urinary argininosuccinate had not been in equilibrium with the urea precursor in this patient, but the plasma [14C]citrulline bore a reasonable precursor-product relationship to the urinary [14C]argininosuccinate.

3. Intravenous [guanidino-14C]arginine given to the patient with argininosuccinic aciduria resulted in a much higher degree of labelling of the plasma globulins than the albumin. This is consistent with a considerable turnover of hepatic arginine, as would be expected with a functioning Krebs-Henseleit urea cycle.

4. These results can be explained with a compartmentation model in which most of the urea is synthesized in the liver, but most of the urinary argininosuccinate is peripheral in origin.
Rapid Transfer of Folic Acid from Blood to Bile in Man, and its Conversion into Folate Coenzymes and into a Pteroylglutamate with Little Biological Activity
Authors: Lavoie A. , Cooper B. A.
Published: August 2015

1. [3H]Folic acid infused intravenously into patients with biliary fistulae appeared promptly in bile, coincident with 131I-labelled Rose Bengal injected simultaneously. The radioactivity was distributed among several fractions of biological folates present in bile and was associated with folic acid and with an unidentified folate which chromatographed on DEAE-Sephadex close to 10-formyltetrahydrofolyl monoglutamate.

2. Based on affinity for DEAE-Sephadex and support of growth of Lactobacillus casei, Streptococcus faecalis and Pediococcus cerevisiae, we have tentatively identified some of the folates of human bile as 10-formyltetrahydrofolate, 10-formylfolate, 5-formyltetrahydrofolate, 5-methyltetrahydrofolate and tetrahydrofolate or 5,10-methylene tetrahydrofolate. After infusion of folic acid, the formyltetrahydrofolates increased more rapidly than did 5-methyltetrahydrofolate.

3. The unidentified radioactive folate contained both the pteridine and p-aminobenzoate portions of folate. It appeared not to support growth of the test microorganisms and not to be bound to a protein or a chain of γ-glutamates. It was present in the bile of a dog injected with [3H]folic acid but was absent from extracts of liver. This material may be a transport form of folate or a special modification imposed on folic acid during transport across the liver.
Lipoprotein Lipase in Human Adipose Tissue
Authors: Elkeles R. S.
Published: August 2015

1. The presence of lipoprotein lipase has been confirmed in acetone-ether extracts of human adipose tissue.

2. The properties of the enzyme appear to be similar to that in rat adipose tissue though it is less active on a weight basis.

3. The presence of a separate monoglyceride lipase has been demonstrated in human adipose tissue.

4. In eluates of human adipose tissue the activity of lipoprotein lipase is dependent on heparin, whereas that of the monoglyceride lipase does not require heparin.

5. No consistent effect of insulin in vitro on the enzyme in human adipose tissue has been demonstrated. Possible reasons for this are discussed.
Albumin and Creatinine Clearances in Renal Disease
Authors: Lavender S. , Bennett J. , Morse P. F. , Polak A.
Published: August 2015

1. The ratio of albumin clearance to creatinine clearance (CA/CC) was determined on 129 occasions in forty patients with a wide variety of renal diseases, both 24 h collections of urine and random mid-morning samples being used. The clearance ratios derived from 24 h urine (24 h CA/CC) and random urine (R CA/CC) were compared with random urine protein concentration, 24 h urine protein excretion and 24 h urine albumin excretion.

2. From these measurements 24 h CA/CC could only be predicted accurately by R CA/CC, particularly when patients with postural proteinuria were excluded.

3. The diurnal variation of CA/CC was investigated in twelve patients with renal disease. The individual values for CA/CC obtained throughout the day were within the limits of prediction of 24 h CA/CC already established. The diurnal variation of CA/CC was considerably less than that of CA or CC alone and also less than that of the rates of protein and albumin excretion.

4. It is suggested that CA/CC is the best readily available measure of ‘glomerular leakiness’ and examples are given of its clinical value. In patients with renal disease 24 h CA/CC could be predicted, in this study, from the clearance ratio based on simultaneous random urine and blood samples.
Variations in Allopurinol Metabolism by Xanthinuric Subjects
Authors: Simmonds H. A. , Levin B. , Cameron J. S.
Published: August 2015

1. The metabolism of allopurinol was studied in a newly discovered patient with xanthinuria.

2. No oxipurinol was detectable in the urine during allopurinol administration, in direct contrast to the results in a patient previously studied by one of us.

3. Other equally discrepant effects of allopurinol on urinary purine and pyrimidine excretion in these two cases are compared with those in the three other recorded cases.
The Effect of Brain Extracts on Urinary Sodium Excretion of the Rat and the Intracellular Sodium Concentration of Renal Tubule Fragments
Authors: Clarkson E. M. , Koutsaimanis K. G. , Davidman M. , Du Bois M. , Penn W. P. , De Wardener H. E.
Published: August 2015

1. Extracts were prepared from bovine hypothalamus and cerebral cortex by gel filtration on Sephadex G-25 and G-50.

2. The vasopressin in the hypothalamic extracts was inactivated with thioglycollate and the effectiveness of inactivation was tested in the alcohol-anaesthetized rat.

3. The inactivated hypothalamic extracts caused a significant rise, and the cortical extracts an insignificant fall, in the urinary sodium excretion of the conscious rat.

4. Incubation of tubule fragments in hypothalamic extracts caused a significant rise in intracellular sodium concentration of the tubules when compared with incubation in Ringer, whereas incubation in cortical extracts caused a rise which was not significant. Nevertheless the rise in intracellular sodium concentration produced by incubating the tubules in hypothalamic extracts was not significantly different from the rise produced by incubation in cortical extracts.
Blood Pressure Changes Produced by Kidney Cross-Transplantation between Spontaneously Hypertensive Rats and Normotensive Rats
Authors: Bianchi G. , Fox U. , Di Francesco G. F. , Giovanetti A. M. , Pagetti D.
Published: August 2015

1. From a single strain of Wistar rats two lines of normotensive rats (NR) and two lines of hypertensive rats (SHR) were developed by selective breeding.

2. One line of normotensive rats and one of hypertensive rats were used as recipients and the remaining two were used as donors for cross-transplantation of kidneys from hypertensive to normotensive rats and vice versa. Transplantations between the two hypertensive lines and the two normotensive ones were carried out to provide animals for control studies.

3. Normotensive recipients of kidneys from SHR developed hypertension whereas the recipients of kidneys from NR remained normotensive. The serum urea changes were equal in both groups.

4. Transplantation of normotensive kidneys reduced the blood pressure of hypertensive recipients, but transplantation of hypertensive kidneys did not alter blood pressure. The serum urea concentrations were higher in the recipients of hypertensive kidneys. These results, obtained in 3–4-month-old rats, indicate that the kidneys of adult hypertensive rats are involved in the maintenance of hypertension.

5. To evaluate whether the kidneys from hypertensive rats may also initiate hypertension, young normotensive recipients were given kidneys taken from the NR or SHR strain while the latter were still normotensive. Transplantation of kidneys from these SHR donors resulted in significantly higher blood pressure values and serum urea concentrations than transplantation of kidneys from NR donors.
The Inhibition of Renin Secretion by Alpha-Adrenergic Stimulation in the Isolated Rat Kidney
Authors: Vandongen R. , Peart W. S.
Published: August 2015

1. The respective role of alpha-adrenergic and beta-adrenergic receptors in mediating the effect of catecholamines on renin secretion was examined in the isolated perfused rat kidney.

2. Noradrenaline, which has combined alpha- and beta-adrenergic activity, stimulated renin secretion only in the presence of the alpha-receptor blocking agent phenoxybenzamine. This stimulatory effect was largely prevented by the addition of the beta-blocking agent, propranolol. The vasoconstrictor action of noradrenaline, and thus the rise in mean renal perfusion pressure, was abolished by phenoxybenzamine. Our previous finding that noradrenaline alone stimulated renin release was inconclusive (Vandongen, Peart & Boyd, 1973).

3. Noradrenaline stimulated renin secretion when calcium was excluded from the perfusion fluid, to which disodium EDTA (25 mmol/l) was added. The vasoconstrictor action of noradrenaline was considerably attenuated under these conditions.

4. Methoxamine, which has only alpha-adrenergic activity, did not increase renin secretion when infused alone or with phenoxybenzamine. The increase in renin secretion after beta-adrenergic stimulation with isoproterenol was significantly suppressed by methoxamine, although this was associated with an increase in mean renal perfusion pressure.

5. These findings indicate the importance of intrarenal beta-adrenergic receptors in the stimulation of renin secretion and suggest that an opposite inhibitory effect on renin secretion follows alpha-adrenergic activity.

6. Although the results do not exclude a direct effect of vascular tone and renal perfusion pressure, it is suggested that the stimulation and inhibition of renin secretion is related to smooth muscle activity by the involvement of a calcium-dependent process similar to that involved in contraction and relaxation. This would accord with the common derivation of the renin-producing and vascular smooth muscle cells
Human Erythrocyte Glutathione Reductase and Glucose 6-Phosphate Dehydrogenase Activities in Normal Subjects and in Persons Exposed to Lead
Authors: Howard J. K.
Published: August 2015

1. Blood lead and erythrocyte glutathione reductase (GSSG-R) and glucose 6-phosphate dehydrogenase (G6P-D) activities were measured in normal subjects and in those with occupational exposure to lead.

2. With increasing blood lead concentration, GSSG-R activity increases and that of G6P-D decreases.

3. It is suggested that these changes represent part of a compensatory mechanism to overcome the reduction of sulphydryl groups by lead ions.
Human Parathyroid Hormone: Immunological Properties of the Amino Terminus and of Synthetic Fragments
Authors: Hendy G. N. , Barling P. M. , O'Riordan J. L. H.
Published: August 2015

1. Immunological assay systems specific to the amino-terminal region of parathyroid hormone were used to study the properties of human parathyroid hormone (HPTH 1-84) and of synthetic peptides. One of these peptides (HPTH 1-34A) had the sequence proposed by Niall, Sauer, Jacobs, Keutmann, Segre, O'Riordan, Aurbach & Potts (1974). The others (HPTH 1-34B and C, synthesized by different methods) had the sequence proposed by Brewer, Fairwell, Ronan, Sizemore & Arnaud (1972).

2. HPTH 1-84 and HPTH 1-34A behaved identically in a number of these systems. In some systems, especially those using antisera obtained by immunizing with HPTH 1-34A, differences were, however, found. These may be due to conformational or other physical differences or to the presence of an immunologically incomplete site in the fragment.

3. In systems in which HPTH 1–84 and HPTH 1-34A behaved identically the peptides with the sequence proposed by Brewer et al. (1972) were of low reactivity by 100–2000-fold.
Uranyl Nitrate Acute Renal Failure in the Dog: Early Changes in Renal Function and Haemodynamics
Authors: Kleinman J. G. , McNeil J. S. , Flamenbaum W.
Published: August 2015

1. Sodium excretion, plasma renin activity (PRA), inulin clearance, total renal blood flow (RBF), renal cortical radiomicrosphere distribution and systemic haemodynamics were examined during the first 3 h after intravenous administration of uranyl nitrate (19.9 μmol/kg body wt.; 10 mg/kg) in the dog.

2. During the 3 h of study after uranyl nitrate, urine flow remained stable or increased, sodium excretion increased approximately fivefold, renal vascular resistance increased threefold, and concordant decreases in RBF and inulin clearance to 40–50% of control values occurred. At 3 h total cortical RBF decreased to 35% of control values and the ratio of blood flow in outer to inner cortical zones also decreased, reflecting outer cortical ischaemia. PRA increased in the first hour after uranyl nitrate and slowly declined thereafter, though not to control values.

3. Respiratory rate, heart rate, mean systemic blood pressure and cardiac output were unchanged after uranyl nitrate, demonstrating that the changes in renal vascular resistance occurred without a change in peripheral vascular resistance.

4. It is postulated that increased renin-angiotensin system activity mediates the change in renal haemodynamics and the consequent fall in glomerular filtration.
Plasma Adenosine 3′:5′-Cyclic Monophosphate Response to Glucagon in Thyroid Disease
Authors: Elkeles R. S. , Lazarus J. H. , Siddle K. , Campbell A. K.
Published: August 2015

1. The plasma adenosine 3′:5′-cyclic monophosphate (cyclic AMP) response to intravenously administered glucagon has been studied in nine hyperthyroid, five hypothyroid and ten euthyroid patients.

2. Concentrations of the nucleotide rose to a peak at 15 min and declined to near basal values by 120 min, the response being greatest in hyperthyroid and least in hypothyroid subjects. The mean peak concentrations were 1028 nmol/l in the hyperthyroid group, 252 nmol/l in the hypothyroid group and 534 nmol/l in the euthyroid group.

3. These results could not be accounted for by differences in serum insulin response.

4. It is suggested that the response of plasma cyclic AMP to glucagon may serve as an index of tissue thyroid status.
Renal Circulatory Responses to General Anaesthesia in the Rabbit: Studies Using Radioactive Microspheres
Authors: Warren D. J. , Ledingham J. G. G.
Published: August 2015

1. Total renal blood flow and its cortical distribution were measured by the radioactive microsphere technique in conscious rabbits and after anaesthesia with pentobarbitone, chloralose-urethane or ether.

2. Pentobarbitone anaesthesia caused a fall of 26% in total renal blood flow, of 26% in superficial cortical flow, and of 24% in deep cortical flow. Sodium excretion rate fell by 33%.

3. Chloralose-urethane anaesthesia caused no change in total or regional renal blood flow, or in sodium excretion.

4. Ether anaesthesia caused an insignificant fall in total renal blood flow, but superficial cortical flow fell by 13 % and deep cortical flow rose by 21 %. Urinary sodium excretion fell by 65%.

5. Possible mechanisms for these changes in response to anaesthesia are discussed.

6. The effects of anaesthetic agents may influence the interpretation of published work on control mechanisms in the renal circulation.
Detection of Low-Renin Hypertension; Evaluation of Out-Patient Renin-Stimulating Methods
Authors: Drayer J. I. M. , Kloppenborg P. W. C. , Benraad T. J.
Published: August 2015

1. Three renin-stimulating methods for detection of low-renin hypertension have been compared. First, renin activity was measured in hospital patients after 5 days of sodium restriction and 3 h ambulation. Secondly, renin activity was measured after frusemide stimulation [0.42 mmol (140 mg) in 18 h] and 3 h ambulation. Thirdly, renin activity was measured after 5 days of chlorthalidone treatment [0.3 mmol (100 mg)/day] and 3 h ambulation. The last two tests were done with the subjects as out-patients without any dietary regimen.

2. In eleven normotensive control subjects and twenty hypertensive patients the results after frusemide were not comparable with those after sodium restriction since the frusemide test did not identify the same renin-suppressed hypertensive subjects as the sodium-restriction procedure.

3. After 5 days of chlorthalidone treatment the renin values in eleven control subjects as well as in thirty-eight hypertensive patients were significantly higher than after sodium restriction. The values obtained after each procedure were closely correlated.

4. Thus the out-patient chlorthalidone procedure identified similar sub-groups of patients as having low- or normal-renin hypertension as did the in-patient sodium-restriction test.
The Assessment of Acid-Base Disturbance in Man by the Use of Carbon Dioxide Titration Curves
Authors: Stoker J. B. , Kappagoda C. T. , Snow H. M. , Linden R. J.
Published: August 2015

1. Carbon dioxide titration curves were determined in vivo in dog and man at various degrees of acute non-respiratory acidaemia and alkalaemia.

2. The slope of the CO2 titration curve (Δlog Pco2/ΔpH) was found to increase with the severity of the acute non-respiratory acidaemia. In states of acute non-respiratory alkalaemia the slope (Δlog Pco2/ΔpH) tended towards unity.

3. A simple scheme based on the CO2 titration curves determined in vivo has been proposed for the assessment of acute acid-base disturbances in man.

4. Carbon dioxide titration curves were also determined in vivo in patients with chronic respiratory and non-respiratory acidaemia and it was found that these curves were not significantly different from those obtained in states of acute acid-base disturbances. It is therefore suggested that the scheme described in this paper is applicable to all acid-base disturbances.
Inhibition of the Pressor and Aldosterone-Releasing Effects of Angiotensin II
Authors: Bumpus F. M. , Khosla M. C.
Published: August 2015

1. Competitive or non-competitive inhibition of the myotropic and pressor response of angiotensin II is dependent on the nature of the substituent in position 8 of the antagonist peptide analogue. Substituents in other positions of the molecule, particularly position 1, contribute greatly to the potency of these antagonists.

2. As is evidenced after adrenalectomy or after blockade with phentolamine and phenoxybenzamine, the initial pressor activity observed with all the antagonistic peptides is partially due to the release of catecholamines and partially to a direct myotropic effect.

3. [Sar1, Thr8]angiotensin II has been found to possess the lowest agonist to antagonist ratio of all antagonists tested.

4. [Des-Asp1, Ile8]angiotensin II selectively and specifically inhibits the release of aldosterone from adrenal cortex. Thus, unlike angiotensin II, this heptapeptide has pronounced organ specificity, suggesting that the heptapeptide (angiotensin III) is the aldosterone-releasing hormone.
The Effect of 1,25-Dihydroxycholecalciferol on Renal Tubular Reabsorption of Phosphate, Intestinal Absorption of Calcium and Bone Histology in Hypophosphataemic Renal Tubular Rickets
Authors: Russell R. G. G. , Smith R. , Preston C. , Walton R. J. , Woods C. G. , Henderson R. G. , Norman A. W.
Published: August 2015

1. 1,25-Dihydroxycholecalciferol (1,25-(OH)2-D3) was given at a dose of 5.0 nmol (2.1 μg) daily by mouth for 4–12 days to three patients with hypophosphataemic (type I), vitamin D-resistant rickets.

2. 1,25-(OH)2-D3 increased intestinal absorption and urinary excretion of calcium without significant effect on the renal handling of phosphate or its plasma concentration.

3. It is concluded that in this type of vitamin D-resistant rickets the renal phosphate abnormality is unlikely to be due to diminished endogenous production of 1,25-(OH)2-D3.

4. The difference between this condition and other hypophosphataemic states is discussed.
Comparative Pharmacology of New Specific Angiotensin Antagonists
Authors: Schoelkens B. A.
Published: August 2015

1. The angiotensin II antagonism by newly synthesized 8-C-phenylglycine analogues of [5-isoleucine]angiotensin II in different preparations was investigated in vitro and in vivo.

2. All analogues competitively inhibited the myotropic effect of angiotensin II on the isolated colon ascendens of the guinea-pig and the stomach of the rat.

3. In normotensive dogs, cats, rabbits, guinea-pigs and rats the blood pressure response to infused angiotensin II was inhibited by the antagonists. The angiotensin II-induced fall in renal blood flow in the dog was blocked during infusion of the analogues. Acute renal hypertension in rats was significantly decreased. Of conscious rats variously with normal blood pressures, spontaneous hypertension and chronic renal hypertension, only in the last group could a marked uniform fall in blood pressure be demonstrated. The central pressor effect of angiotensin II was also inhibited in conscious rats.

4. 8-C-Phenylglycine analogues of [5-isoleucine]-angiotensin II exhibit a specific antagonistic activity to endogenous and exogenous angiotensin II.
Effect of Single and Combined Infusions of Angiotensin II and Aldosterone on Colonic Potential Difference, Blood Pressure and Renal Function, in Patients with Adrenal Deficiency
Authors: Efstratopoulos A. D. , Peart W. S.
Published: August 2015

1. The effect of single and combined infusions of angiotensin and aldosterone on colonic potential difference, blood pressure and renal function was studied in two normal male subjects and four female patients with adrenal deficiency maintained only on cortisone.

2. Aldosterone had its usual effect on colonic potential difference and it was possible to show that angiotensin had a small but definite effect of its own in the absence of aldosterone. The two hormones produced a summation response when given together.

3. The effects on renal function in two normal young male subjects were similar to those known previously. The response of the patients was different and probably reflected a number of factors, such as age, sex and long-standing adrenal deficiency.

4. Although the numbers were small, both normal subjects and patients showed a significantly greater rise of blood pressure with combined infusions of angiotensin and aldosterone than with angiotensin alone. The plasma concentrations of angiotensin were similar with both types of infusion, and so increased sensitivity to angiotensin in the presence of aldosterone is postulated.
Feedback Regulation of 25-Hydroxycholecalciferol Metabolism by Vitamin D3
Authors: Evans I. M. A. , Colston K. W. , Galante L. , MacIntyre I.
Published: August 2015

1. In vitamin D-deficient chicks both vitamin D3 and 1α-hydroxycholecalciferol markedly decrease renal 1-hydroxylase activity and induce 24-hydroxylase activity.

2. Actinomycin D abolishes both effects.

3. These results are consistent with feedback regulation of vitamin D3 metabolism by a direct nuclear action of the vitamin or its metabolites on the kidney cells.
Ammonia and Urea Transport by the Excluded Human Colon
Authors: Bown R. L. , Gibson J. A. , Fenton J. C. B. , Snedden W. , Clark M. L. , Sladen G. E.
Published: August 2015

1. Ammonia and urea transport across the colonic mucosa was studied by a perfusion technique in four subjects with colonic exclusion for chronic hepatic encephalopathy.

2. Reduction of luminal pH inhibited net and unidirectional transport of ammonia from lumen to plasma, but net absorption from high luminal concentrations persisted at low pH.

3. Neither addition of urea to the perfusate nor intravenous infusion of urea produced a consistent increase in the colonic excretion of ammonia when ammonia-free solutions were perfused.

4. In one subject intravenous infusion of [15N]-ammonium chloride produced rapid labelling of colonic effluent ammonia and within 60 min the specific enrichments of ammonia in effluent and in arterial plasma were approximately equal.

5. During perfusion of nitrogen-free solutions, only small amounts of urea appeared in the effluent, suggesting limited permeability of the colonic mucosa to urea.

6. These results are discussed in relation to the equilibration of ammonia across the colonic mucosa by both ionic and non-ionic diffusion. The lack of evidence of ‘juxtamucosal’ (as opposed to luminal) ureolysis is in contrast to other observations on the intact colon. The possible reasons for and implications of this discrepancy are discussed.
The Selective Inhibition of Chenodeoxycholate Synthesis by Cholate Metabolites in Man
Authors: Pomare E. W. , Low-Beer T. S.
Published: August 2015

1. Seven normal volunteers took 0.28–0.42 mmol (100–150 mg) of deoxycholate by mouth. This resulted in a reduced proportion of chenodeoxycholate in bile and an increased proportion of deoxycholate. Cholate was unchanged. 2. Cholate and chenodeoxycholate pools and rates of synthesis were determined in four of the subjects by simultaneously labelling each pool with relabelled bile acids. The chenodeoxycholate pool and rate of synthesis decreased after deoxycholate administration. Cholate synthesis and pool size did not change appreciably.

3. The proportion of deoxycholate in bile samples of sixty-two subjects with intact enterohepatic circulation was found to be inversely related to the proportion of chenodeoxycholate in bile, but not to the cholate.

4. It is suggested that inhibition of chenodeoxycholate synthesis by deoxycholate, the principal bacterial product of cholate, regulates the size of the chenodeoxycholate pool independently of the total amount of bile salt.
Angiotensin Blockade in Studies of the Feedback Control of Renin Release in Rats and Rabbits
Authors: Stokes G. S. , Oates Helen F. , Weber M. A.
Published: August 2015

1. In rabbits actively immunized against angiotensin II (AII), the appearance of anti-AII antibodies was associated with a rise in plasma renin activity (PRA), which did not occur in mock-immunized controls.

2. In conscious rabbits, infusion of the angiotensin inhibitor, Sar1-Ala8-angiotensin II (P-113), at rates of 0.055, 0.22 or 1.1 nmol min−1 kg−1 into the renal artery, caused dose-related increases in arterial PRA and renal arteriovenous PRA difference. Renal blood flow fell with the high dose, but not with the low or medium doses. A fall in arterial pressure, asynchronous with peak renin secretion, accompanied the medium- and high-dose infusions.

3. Intravenous infusion of inhibitor P-113, 5.5 nmol min−1 kg−1, into anaesthetized rats produced highly significant increases in PRA and plasma renin concentration without reduction in arterial pressure. There were no changes in PRA or plasma renin concentration in saline-infused control rats.

4. These findings suggest that AII blockade interrupts a negative feedback loop controlling renin secretion.
Factors affecting the Metabolic Production of Methylguanidine
Authors: Gonella M. , Barsotti G. , Lupetti S. , Giovannetti S.
Published: August 2015

1. Methylguanidine administered orally to normal volunteers was almost completely recovered in the urine, indicating that it is absorbed in the gastrointestinal tract and is not converted into other compounds. In normal persons at least, its urinary output therefore corresponds to its metabolic production rate plus the amount ingested.

2. In normal persons, diets based on foods not containing methylguanidine (e.g. vegetarian, protein-free and milk-egg diets) caused a fall in the urinary output of methylguanidine as compared with the output of the same subjects on a free diet. Conversely, higher amounts of methylguanidine were excreted on a diet rich in broth and in boiled beef, which contain large amounts of methylguanidine formed from the oxidation of creatinine, caused by boiling.

3. Oral administration of creatinine to normal volunteers induced an immediate and marked increase in urinary excretion of methylguanidine, and the ingestion of [methyl-14C]creatinine by uraemic patients was followed by the urinary excretion of labelled methylguanidine. These findings indicate that creatinine is partly converted into methylguanidine in both normal and uraemic subjects and accounts for the high metabolic production of methylguanidine in patients with renal failure, in whom the body pool of creatinine is high.

4. Creatinine, incubated at 38°C for 24 h in Krebs bicarbonate solution (pH 7.38) through which was bubbled oxygen with 15% carbon dioxide, was partially oxidized to methylguanidine. This raises the possibility that even in vivo such a conversion may occur ‘non-enzymatically’.
Protein Synthetic Activity of Membrane-Bound and Free Ribosomes from Parathyroid Glands of Dogs
Authors: Alford F. P. , Cook P. S. , Swenson R. S. , Reaven G. M.
Published: August 2015

1. Membrane-bound and free polyribosomes were isolated from parathyroid glands of normal dogs by a discontinuous density-gradient technique.

2. The conditions necessary for optimum incorporation by bound and free ribosomes of [3H]-phenylalanine into protein were determined for asays in vitro directed by both endogenous messenger ribonucleic acid (mRNA) and polyuridylic acid [poly(U)].

3. When the specific cofactors were available in optimum amounts, the rate of incorporation of amino acids into protein was directly proportional to the number of ribosomes present. This applied to assays directed by endogenous mRNA and poly-(U).

4. The results indicate that it is possible to isolate and directly study the protein synthetic activity of membrane-bound and free parathyroid ribosomes.
The Relationship of Body Fat Content to Deep Muscle Temperature and Isometric Endurance in Man
Authors: Petrofsky J. S. , Lind A. R.
Published: August 2015

1. The relationship between body fat content, isometric endurance and deep muscle temperature was assessed in eight male and female volunteers trained to static effort.

2. Muscle temperature, measured in the belly of the brachioradialis muscle, was found to be directly related to the subjects' body fat content.

3. Associated with a reduction in body fat content, there was a marked decrease in deep muscle temperature and an increase in isometric endurance of the hand-grip muscles; no change in strength was noted.

4. Conversely, an increase in body fat content resulted in an increase in deep muscle temperature and a decrease in isometric endurance.

5. When muscle temperature was stabilized before and after weight loss by immersing the forearm in water at 37°C, a reduction in body fat no longer influenced endurance.

6. It was concluded that the change in isometric endurance associated with either loss or gain of weight can be accounted for entirely by the changes in muscle temperature.
Effects of Inhaled Prostaglandins E1, E2 and F2α on the Airway Resistance of Healthy and Asthmatic Man
Authors: Smith A. P. , Cuthbert M. F. , Dunlop L. S.
Published: August 2015

1. Changes in specific airway conductance after the inhalation of aerosols of prostaglandins (PG) E1, E2 and F2α were investigated in healthy and asthmatic subjects.

2. Inhalation of 155 nmol (55 μg) of PGE1 or 156 nmol (55 μg) of PGE2 resulted in consistent minor bronchodilatation in healthy subjects, but in asthmatic patients airway conductance increased significantly, along with subjective improvement. Isoprenaline (988 nmol; 550 μg) inhalation resulted in a similar increase in conductance to that obtained after these two prostaglandins, whereas a control aerosol had no effect. In contrast to the isoprenaline aerosol, both PGE1 and PGE2 were highly irritant to inhale. It was concluded that this made them unsuitable for therapeutic use.

3. Prostaglandin F2α inhalation resulted in a dose-related bronchoconstriction in healthy and asthmatic subjects. Asthmatics were approximately 150 times more sensitive to PGF2α than were the healthy subjects but there was very wide and significant variation in the sensitivity of the asthmatic subjects. In contrast the asthmatic subjects were only 8.5 times more sensitive to histamine than the healthy subjects with less variation in response of individual subjects. The reasons for the hyper-reactivity of asthmatic subjects to PGF2α is unknown and no correlation could be drawn between increased sensitivity and age, type of asthma, or treatment.

4. The effects of disodium cromoglycate, flufenamic acid, atropine methonitrate, PGE2 and isoprenaline on PGF2α-induced bronchoconstriction were investigated in healthy subjects. Prostaglandin E2 reversed PGF2α-induced bronchoconstriction, as did isoprenaline, but prior treatment with the other drugs had no effect in preventing bronchoconstriction.
Hypertensive and Renin-Suppressing Activities of Propranolol in Hypertensive Patients
Authors: Leonetti G. , Mayer Genevieve , Morganti A. , Terzoli Laura , Zanchetti A. , Bianchetti G. , Di Salle E. , Morselli P. L. , Chidsey C. A.
Published: August 2015

1. In patients with mild or moderate essential hypertension, oral propranolol, given in incremental doses, produced a moderate but significant lowering of blood pressure which was correlated with the concentration of propranolol in plasma.

2. Propranolol also reduced plasma renin activity (PRA) in the supine posture, on standing and after intravenous frusemide. However, ‘supine’ and ‘frusemide’ PRA values were markedly reduced at a plasma concentration of propranolol that had little effect on blood pressure.

3. On administration of propranolol there was little correlation between blood pressure decrease and PRA suppression, and even less between pretreatment PRA values and hypotensive response.

4. It is concluded that in patients with mild and moderate hypertension and low or normal plasma renin activity, suppression of PRA is not an important determinant of the hypotensive response to propranolol.
The Role of the Renin—Angiotensin—Aldosterone System in Cardiovascular Homeostasis in Normal Man
Authors: Haber E. , Sancho J. , Re R. , Burton J. , Barger A. C.
Published: August 2015

1. To examine the role of angiotensin II in the maintenance of blood pressure and control of aldosterone secretion, eight normal human subjects were studied on a tilt table in sodium-replete and sodium-depleted states, before and after the administration of an angiotensin converting-enzyme inhibitor (CEI).

2. Administration of CEI was followed by a marked fall in blood pressure on tilting in sodium-depleted, but not in sodium-replete, subjects. CEI administration also resulted in a rise in plasma renin activity in the supine position, in the absence of haemodynamic change. The rise in plasma aldosterone observed both in response to tilting and sodium depletion did not occur after CEI, even though plasma renin activities were higher.

3. These results indicate that: (a) angiotensin II is essential for blood pressure control in the sodium-depleted individual; (b) angiotensin II exerts direct feedback control on renin secretion; (c) angiotensin II is the primary stimulus to aldosterone secretion in response to both sodium depletion and posture.
Renin-Suppressive Potency of Various Beta-Adrenergic Blocking Agents at Supine Rest and during Upright Exercise
Authors: Bühler F. R. , Marbet G. , Patel U. , Burkart F.
Published: August 2015

1. Renin responses to different types of beta-adrenergic blocking agents were compared in eight normal volunteers at supine rest and during moderate upright exercise.

2. Comparable beta-adrenergic blockade was achieved with equipotent cardiodeceleratory doses of 100 mg of propranolol, 400 mg of practolol, 100 mg of oxprenolol, 10 mg of timolol, 5 mg of pindolol or 100 mg of ICI 66082.

3. All beta-blocking agents tested significantly and markedly reduced plasma renin activity during upright exercise. Renin suppression was not related to either β1- or β2-type receptor blocking action.

4. Renin levels at rest were generally reduced by the blocking drugs, but these responses did not reach significance for oxprenolol and pindolol. With both these drugs, lesser suppressibility of basal renin may be due to their inherent sympathomimetic activity.

5. The results suggest that different types of beta-blocking agents suppress plasma renin activity and therefore that they all may lower blood pressure through reduction of angiotensin vasoconstriction.
Effect of Volume Depletion and Subsequent Propranolol Treatment on Blood Pressure and Plasma Renin Activity in Patients with Essential and with Renovascular Hypertension
Authors: Geyskes G. G. , Boer P. , Leenen F. H. H. , Mees E. J. Dorhout
Published: August 2015

1. In nineteen patients, five with unilateral renal artery stenosis and fourteen with essential hypertension (WHO grades I–II), blood pressure, plasma and extracellular fluid volumes and plasma renin activity were studied at the end of three sequential periods: (a) after at least 3 days on a 60 mmol Na+ diet; (b) after 3 days of salt depletion induced with a diuretic and sustained on a 20 mmol Na+ diet; (c) after 3 days during which the 20 mmol Na+ diet was continued and beta-receptor blockade was induced by increasing dosages of propranolol up to 320 mg daily.

2. After sodium depletion extracellular fluid volume and plasma volume decreased and plasma renin activity increased; blood pressure did not change significantly.

3. After adding propranolol, plasma volume and extracellular fluid volume remained low, and there was a significant decrease in plasma renin activity and blood pressure.

4. No correlation could be demonstrated between changes of blood pressure and plasma renin activity.

5. When the responses of the five patients with renal artery stenosis were compared with those of the fourteen patients with essential hypertension, no significant differences were found.

6. Propranolol has a strong anti-hypertensive effect after Na+ depletion, irrespective of the absolute activities of plasma renin.
Blood Pressure Decrease and Responsiveness to Renin-Releasing Stimuli under Increasing Doses of Propranolol in Patients with Essential Hypertension
Authors: Leonetti G. , Mayer G. , Morganti A. , Terzoli L. , Zanchetti A. , Morselli P. L. , Di Salle E. , Chidsey C. A.
Published: August 2015

1. Stepwise increases of oral doses of propranolol produced both a significant lowering of blood pressure and suppression of plasma renin activity in sixteen patients with mild or moderate normal-renin essential hypertension.

2. The hypotensive and the renin-suppressive actions of propranolol were differently related to plasma propranolol concentrations. At the lowest propranolol concentrations (15–40 nmol/l), there was almost no decrease in blood pressure whereas plasma renin activity and responsiveness to renin-releasing stimuli (standing, intravenous frusemide) were already strongly depressed (greater than 50%). Therefore in a large number of normal-renin hypertensive patients under small doses of propranolol, the renin-suppressive action of the drug can be dissociated from the hypotensive effect. Dissociation of the two effects, though in the opposite way, was also observed in three of four low-renin hypertensive patients, whose blood pressure was decreased by propranolol without further reduction of the already suppressed plasma renin activity.

3. It is concluded that in patients with mild and moderate hypertension and low or normal plasma renin activity, the hypotensive effect of propranolol cannot be attributed to suppression of renin activity. These conclusions do not necessarily apply to high-renin hypertensive patients.
Beta-Blocking Drugs and Renin Secretion in the Anaesthetized Dog
Authors: Imbs J. L. , Kraetz J. , Schmidt M. , Desaulles E. , Schwartz J.
Published: August 2015

1. The effect of propranolol and sotalol on renin secretion was studied in the anaesthetized dog.

2. Beta-adrenergic blockade did not modify basal renin secretion and did not affect the rise of renin secretion induced by haemorrhage or aortic constriction.

3. Beta-adrenergic blockade diminished the rise in renin secretion induced by stimulation of the renal nerves.
Pathogenesis and Prevention of Stroke in Spontaneously Hypertensive Rats
Authors: Okamoto K. , Hazama F. , Yamori Y. , Haebara H. , Nagaoka A.
Published: August 2015

1. A colony of stroke-prone spontaneously hypertensive rats has been developed by selective breeding.

2. These animals developed severe hypertension early in life, the magnitude of the hypertension being closely related to the incidence of stroke.

3. No evidence was obtained of any humoral factor responsible for strokes.

4. Local factors predisposing to stroke were a scanty arterial supply with characteristic recurrent branching of long and large arteries, together with increased vascular permeability, angio-necrosis, and formation of microaneurysms.

5. Strokes could be prevented by adequate anti-hypertensive therapy from an early age.
A Pilot Trial of Treatment for Mild Hypertension; Interim Report of the Medical Research Council's Trial in Britain
Authors: Miall W. E. , Brennan P. J.
Published: August 2015

Progress in the pilot phase of the British multi-centre randomized controlled trial of treatment for patients with mild hypertension is described.
Effect of Pyratrione (a Tyrosine Hydroxylase Inhibitor) in Essential Hypertension
Authors: Kimura T. , Takahashi E. , Ozawa M. , Uchiyama S. , Maekawa S. , Yashima O. , Sato M.
Published: August 2015

1. A clinical study of pyratrione, a tyrosine hydroxylase inhibitor, has been carried out in essential hypertension.

2. Out of thirty-nine patients who received pyratrione, twenty-eight showed a significant decrease in blood pressure.
The Use of Minoxidil, an Experimental Arteriolar Dilator, in 510 Patients with Refractory Hypertension
Authors: Martin W. B. , Zins G. R. , Freyburger W. A.
Published: August 2015

1. Minoxidil, an experimental arteriolar dilator, has been used in conjunction with a diuretic and a sympathetic nervous system suppressant in 510 patients with refractory hypertension, of whom 323 remain on treatment. The results in two of a total of twenty aetiological groups are described.

2. Of eighty-eight patients with refractory hypertension who were on maintenance haemodialysis when minoxidil was first administered, forty-six currently remain on treatment. In these the average blood pressure fell to 150/100 mmHg from an average of 190/130 mmHg before minoxidil. Healing occurred in the nineteen who had had grade 3 or 4 optic fundi. Side effects resulted in discontinuation of the drug in four of the eighty-eight patients.

3. Thirty-five patients with essential hypertension and good renal function were treated for from 3 to 12 months. The supine blood pressures before minoxidil averaged 280/128 mmHg and averaged 160/97 mmHg whilst the drug was given. The serum creatinine concentration did not change significantly. The optic fundi improved in nine; in nine others episodes of congestive heart failure were reduced in frequency.

4. If careful attention is directed to salt balance and to heart rate, minoxidil may help control otherwise refractory hypertension.
Central Regulation of Arterial Blood Pressure
Authors: Philippu A.
Published: August 2015

1. Cats were anaesthetized with pentobarbitone sodium. The hypothalamus was superfused with drugs through a push-pull cannula and electrically stimulated with the non-insulated tip of the cannula. In another series of experiments, the hypothalamus was stimulated with a monopolar electrode and the nucleus of the solitary tract superfused with drugs through a push-pull cannula.

2. Superfusion of the hypothalamus with alpha-adrenoreceptor blocking agents (piperoxan or tolazoline) decreased the pressor responses to hypothalamic stimulation. Superfusion with low concentrations of clonidine increased, whereas superfusion with higher concentrations of this drug diminished, the rise of blood pressure during hypothalamic stimulation. Muscarinic agents (oxotremorine, muscarine or AHR 602) decreased the pressor responses to hypothalamic stimulation. The inhibitory effects of the muscarinic compounds were abolished by superfusing the hypothalamus with methylatropine. Superfusion with nicotinic agents (1,1-dimethyl-4-phenylpiperazinium, or carbachol) enhanced the pressor responses to hypothalamic stimulation. The enhancement of the pressor responses by these drugs was completely inhibited by superfusion of the hypothalamus with hexamethonium.

3. Superfusion of the nucleus of the solitary tract with tolazoline enhanced the pressor responses to hypothalamic stimulation. The pressor responses were reduced during superfusion of the nucleus of the solitary tract with clonidine.
Central Neurohormonal Mechanisms in Spontaneously Hypertensive Rats Compared with Human Essential Hypertension
Authors: Folkow B.
Published: August 2015

Consideration of the results obtained in studies of spontaneously hypertensive rats indicates that these animals can serve as useful models for perhaps the most common type of essential hypertension of man. Other variants of essential hypertension probably occur where the relative balance between the genetic elements predisposing to high blood pressure may be somewhat different.
Neural Control of Renin Release
Authors: Zanchetti A. , Stella A.
Published: August 2015

1. Factors involved in the neural control of renin release have been reviewed.

2. Experimental evidence has been obtained that sympathetic stimulation releases renin from the kidney independently of local vasomotor changes.

3. The reflex control of renin release on postural change has been established.

4. The effect of diuretics on renin release has been studied and evidence of neural and non-neural mechanisms obtained.

5. The effect of suprarenal aortic stenosis has been studied; the findings suggest that renin release is in some way dependent on neural mechanisms.

6. The pathological significance of the neural control of renin release has been discussed.
Plasma Noradrenaline Concentration and Blood Pressure in Essential Hypertension, Phaeochromocytoma and Depression
Authors: Louis W. J. , Doyle A. E. , Anavekar S. N.
Published: August 2015

1. Mean plasma noradrenaline concentration was elevated in forty-four patients with established essential hypertension. Eighteen of these hypertensive patients had resting plasma noradrenaline concentrations in the normal range.

2. Patients with endogenous depression had higher mean plasma noradrenaline concentrations but significantly lower blood pressure than patients with essential hypertension.

3. Patients with phaeochromocytoma had plasma noradrenaline concentrations twenty-eight times greater than those found in essential hypertension, but blood pressures were less than 20% higher.

4. It is concluded that excess of sympathetic drive only partly explains the level of the blood pressure in essential hypertension.