bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Effects of Selective and Non-Selective Prostaglandin-Synthesis Inhibition on the Pharmacological Responses to Captopril in Patients with Essential Hypertension
Authors: Salvetti A. , Pedrinelli R. , Magagna A. , Ugenti P.
Published: August 2015

1. The finding that sulindac, in contrast to indomethacin, does not inhibit renal prostaglandins synthesis in humans, prompted us to study the role that systemic and/or renal prostaglandins can play in the pharmacological responses to captopril. According to a randomized cross-over design, we compared the short-term (1 week) effect of indomethacin (50 mg twice daily) and of sulindac (200 mg twice daily) on blood pressure, plasma renin activity (PRA), angiotensin converting enzyme (ACE), serum thromboxane (TX) B2 and urinary 6-keto PGF1α of five essential hypertensive patients on chronic treatment with captopril (100-200 mg twice daily).

2. Indomethacin significantly increased systolic (P < 0.02) and diastolic (P < 0.02) blood pressure, decreased PRA (P < 0.05), serum TXB2 (P < 0.001) and urinary 6-keto PGF1α (P < 0.001) and did not change ACE.

3. Sulindac reduced PRA (P < 0.02) and serum TXB2 (P < 0.001) to the same extent as indomethacin, but it did not change ACE and urinary 6-keto PGF1α, and caused only a small and significant increment of blood pressure.

4. These preliminary findings confirm that sulindac selectivity inhibits prostaglandins synthesis and seem to indicate that renal PGI2 can play a role in the antihypertensive action of captopril.
Involvement of Prostaglandins in the Actions of Captopril
Authors: Witzgall H. , Scherer B. , Weber P. C.
Published: August 2015

1. Haemodynamic and hormonal actions of 100 mg of captopril (SQ 14 225) orally were tested in 12 healthy volunteers with and without indomethacin pretreatment.

2. Without indomethacin, mean arterial blood pressure was reduced at 30 and 60 min after captopril (P < 0.02). Heart rate did not change. Plasma renin activity (PRA) increased (P < 0.002), and plasma and urinary aldosterone as well as plasma 18-hydroxycorticosterone (18- OH-B) decreased after captopril (P < 0.02). Prostaglandin (PG) E2, kallikrein, urine volume, sodium and potassium excretion rates remained constant after captopril.

3. Under indomethacin pretreatment, blood pressure was reduced to a smaller degree at 30 and 60 min after captopril (P < 0.05). Heart rate was constantly lower than without indomethacin (P < 0.05). Indomethacin decreased basal PGE2 and kallikrein excretion (P < 0.02) and reduced basal PRA as well as the increase of PRA after captopril (P < 0.05). Basal mineralocorticoid levels were significantly lower than without indomethacin. Aldosterone did not decrease further after captopril, and 18-OH-B fell only slightly.

4. The results suggest that prostaglandins may be involved in the haemodynamic and hormonal actions of captopril.
Effect of Age on Vascular α-Adrenoceptor Responsiveness in Man
Authors: Elliott Henry L. , Sumner David J. , McLean Kathleen , Rubin Peter C. , Reid John L.
Published: August 2015

1. The responsiveness of α-receptors was compared in six young and six healthy elderly subjects by evaluating the haemodynamic effects of the a, antagonist prazosin and the pressor responses to the a, agonist phenylephrine.

2. Oral prazosin (1 mg) lowered erect (but not supine) blood pressure in both groups by a comparable amount: in young and old groups the respective maximal falls in systolic pressure were 19.5 ± 15.7 and 29.3 ± 11.4 mmHg (mean ± sd) and for diastolic pressure the maximal falls were 13 ± 13.3 and 18 ± 11.1 mmHg.

3. This similar fall in blood pressure occurred in association with a significantly different heart rate response: in the young group mean heart rate increased to 103 beats/min but there was no corresponding increase in the elderly group, which had a mean heart rate of 80 beats/min.

4. Log dose-response curves were derived from incremental intravenous infusions of phenylephrine, and the doses required to raise mean arterial pressure by 20 mmHg (PD20) were compared: the mean PD20 was significantly different in the two groups: 2.5 ± 1.6 in the young compared with 4.6 ± 2.3 μg min−1 kg−1 in the elderly, consistent with reduced pressor responsiveness in the elderly.

5. No significant difference in PD20 was apparent when pressor responsiveness was determined after prazosin, but the elderly required a significantly smaller increase in phenylephrine dosage to overcome prazosin's α-receptor-blocking effects.

6. Although there is no evidence of an age-related increase in the sensitivity of α-adrenoceptor-mediated vasoconstriction, the results are not inconsistent with an age-related reduction in α-adrenoceptor responsiveness.
Changes of Plasma and Cerebrospinal Fluid Noradrenaline during Frusemide Administration and Acute Renal Artery Constriction in Dogs
Authors: Masuyama Yoshiaki , Ueno Yuji , Arita Mikio , Suruda Hidetoshi , Mohara Osamu
Published: August 2015

1. The effects of circulating angiotensin II on cerebrospinal fluid and plasma noradrenaline during frusemide administration and acute renal artery constriction were studied in dogs.

2. The administration of frusemide produced significant increases in cerebrospinal fluid and plasma noradrenaline. Intravertebral artery infusion of [Sar1, Ala8]angiotensin II (saralasin) significantly suppressed the frusemide-induced increases in cerebrospinal and plasma noradrenaline and resulted in a fall in arterial blood pressure.

3. Acute renal artery constriction produced the marked elevation of plasma noradrenaline and arterial blood pressure, although no significant increase was found in cerebrospinal fluid noradrenaline. Though intravertebral artery infusion of saralasin did not affect cerebrospinal fluid and plasma noradrenaline, intravenous infusion of saralasin reduced the increases in arterial blood pressure and plasma noradrenaline induced by acute renal artery constriction.

4. Plasma volume was significantly reduced by frusemide administration, but unchanged by acute renal artery constriction.

5. Therefore it is suggested that circulating angiotensin II may contribute to the regulation of blood pressure at least partially by acting on the central nervous system in the sodium- and volume-depleted states. However, the renin-angiotensin system appears to play a rather direct role in the mechanism of hypertension induced by renal artery constriction, not through the action of angiotensin II on the central sympathetic nervous system.
Index for Normalization of Blood Volume
Authors: Chau Nguyen PH. , Tarazi Robert C. , Fouad Fetnat M. , Safar Michel E. , Birkenhäger Willem H. , De Leeuw Peter W.
Published: August 2015

1. A general method for the development of a blood volume index was devised to allow inter-individual comparisons.

2. An accurate and acceptable blood volume index had to fulfil certain criteria; it had to be (1) not correlated with body size, (2) highly correlated with blood volume, (3) either dimension-less or expressible in units of length or of surface area and (4) simple to calculate.

3. Available data, from the Broussais Hospital, Paris, the Zuiderziekenhuis, Rotterdam and the Cleveland Clinic, Cleveland, Ohio, included six groups of normal subjects, male essential hypertensive patients and female essential hypertensive patients.

4. Extensive calculations, based on the available data, indicated that the equation BVI = BV/(a√H.W) (BVI = blood volume index, BV = blood volume, H = body height, W = body weight and a = a constant depending on the chosen units) was the simplest index which satisfied the above requirements.

5. As the equation SA = 0.165 √(H.W) (SA = body surface area, in m2, H in m and W in kg) is almost identical with the Dubois & Dubois formula predicting body surface area from height and weight, one may choose a = 0165 and the index BVI = BV/[0.165 √(H.W)] (/H in m, W in kg, BV in ml and BVI in ml/m2). Thus blood volume is referred to body surface area.

6. Blood volume referred to unit body surface area appears, at the present, to be the most appropriate ‘blood volume index’. However, studies of data from larger groups and from more centres are needed to confirm this conclusion.
Haemodynamic Alterations Triggered by Blood Pressure Assessments by the Doctor
Authors: Mancia G. , Bertinieri G. , Grassi G. , Pomidossi G. , Parati G. , Gregorini L. , Ferrari A. , Zanchetti A.
Published: August 2015

1. The blood pressure and heart rate alterations associated with blood pressure assessments by the doctor (cuff method) were studied in 48 normotensive and essential hypertensive in-patients under 24 h direct blood pressure recording.

2. In almost all patients the doctor's arrival to measure blood pressure induced an immediate pressor and tachycardic response that was maximal within 2–4 min and then declined slightly. Both values were still elevated 10 min after the doctor's arrival and even after his departure.

3. Both the pressor and tachycardic responses showed large interindividual differences in magnitude; the average responses, however, were similar for the normotensive and the hypertensive groups of subjects. They were also similar for the first and the second blood pressure assessment performed by the same doctor.

4. These findings outline some of the limitations of the traditional blood pressure assessment procedure and suggest caution in interpreting its results.
Dietary Sodium Restriction in Normotensive Subjects and Patients with Essential Hypertension
Authors: MacGregor G. A. , Markandu N. D. , Sagnella G. A.
Published: August 2015

1. Seventy-seven patients with essential hypertension and 28 normotensive subjects were studied on their normal diet (ND), on the fifth day of a high sodium diet (HS) (350 mmol/day) and on the fifth day of a low sodium diet (LS) (10 mmol/day).

2. With an increase in sodium intake, there was no change in mean blood pressure either in the normotensive subjects (ND, 120/75 ± 2.4/1.7 mmHg—HS, 119/75 ± 2.7/1.7 mmHg) or in the hypertensive subjects (ND, 173/110 ± 2.5/1.3 mmHg—HS, 174/110 ± 2.5/1.4 mmHg).

3. On the fifth day of the low sodium diet there was no change in mean blood pressure in the normotensive subjects (ND, 120/75 ± 2.5/1.7 mmHg—LS, 116/76 ± 2.7/2.0 mmHg). In contrast, the hypertensive group on the fifth day of the low salt diet had a significant fall in supine mean blood pressure compared with those on the normal diet (ND, 173/110 ± 2.5/1.3—LS, 155/102 ± 2.2/1.3 mmHg; P < 0.001). The fall in mean blood pressure was 10.8 ± 1.1 mmHg (8.4%).

4. There was a significant correlation between the fall in blood pressure with the low sodium diet and the level of blood pressure on the normal diet (r = 0.52; P < 0.001) and a significant inverse correlation with the fall in blood pressure on the low sodium diet and the rise in plasma renin activity from the normal to low sodium diet (r = −0.36; P < 0.001).

5. Nineteen patients with mild to moderate essential hypertension were studied in a double-blind randomized crossover study of moderate dietary sodium restriction using slow sodium and placebo for 1 month each. On the fourth week of placebo (mean 24 h UNa 86 ± 9 mmol), mean supine blood pressure was 7.1 mmHg lower (6.1%), P < 0.001 compared with the fourth week of slow sodium (mean 24 h UNa 162 ± 9 mmol).

6. Moderate dietary sodium restriction over 1 month caused a fall in blood pressure in patients with essential hypertension. A more severe reduction in sodium intake for a shorter period of time lowered blood pressure in hypertensive but not normotensive subjects. Part of the mechanism of this blood pressure reduction with sodium restriction appeared to be related to the severity of the hypertension and to suppression of the renin-angiotensin system.
Rate of Hypertension Return after Withdrawal of Prolonged Antihypertensive Therapy
Authors: Wassertheil-Smoller Sylvia , Langford H. , Blaufox M. D. , Oberman A. , Babcock Connie , Hotchkiss Jeanne
Published: August 2015

1. Among 160 patients who were withdrawn from antihypertensive therapy after long-term treatment, 42% had to be restarted on medication within 8 months of the withdrawal. Average time to return to medication was 16 weeks.

2. A significantly higher proportion of more severe hypertensive patients had to be restarted on drugs than of mild hypertensive patients (25% versus 75%).

3. For mild hypertensive patients, there were no differences in rate of return to drugs by age, race, sex, or obesity status. For the more severe hypertensive patients failure rate was considerably higher among the obese than the non-obese in each sex-race group.
Changes in Liver Glycogen and Glycolytic Intermediates during Abdominal Surgery in Man
Authors: Hall G. M. , Traynor Celine , Paterson J. L.
Published: August 2015

1. Changes in liver glycogen and glycolytic intermediates were determined in ten patients undergoing abdominal surgery for carcinoma of the colon.

2. One hour of surgery resulted in a 19% decrease in liver glycogen, together with an increase in hepatic glucose 6-phosphate and glucose concentrations.

3. Blood glucose increased from 5.01 to 6.67 mmol/l during the hour between liver biopsies.

4. We conclude that the hyperglycaemia of surgery is associated with stimulation of hepatic glycogenolysis.
Proteolytic Enzymes, their Inhibitors and Lung Diseases
Authors: Stockley R. A.
Published: August 2015

The pathogenesis of many acute and chronic lung diseases remains a mystery. However, recent years have seen a rapidly increasing interest in the role of proteolytic enzymes and their inhibitors in modifying the inflammatory, destructive and reparative changes that occur in the lung. Much of this interest owes its existence to two observations in the early 1960s: firstly, the recognition that subjects with an inherited deficiency of α1-antitrypsin (α1-AT; the main serum inhibitor of proteolytic enzymes) had a high incidence of pulmonary emphysema [1], and secondly the demonstration by Gross et al. [2] that a proteolytic enzyme (papain) was capable of producing lesions similar to emphysema in experimental animals.

These observations ultimately led to the proteinase—anti-proteinase theory of emphysema, which predicts that a state of balance occurs in the healthy lung in which the proteolytic enzyme inhibitors functionally equal or exceed the enzymes. Destructive lung disease occurs when the enzymes functionally exceed the inhibitors such that they remain active within the lung, resulting in digestion of connective tissue. This general concept of a disturbed proteinase—anti-proteinase balance within the lung has been recently applied to many other lung diseases, and some will be mentioned later. However, it is in the study of chronic bronchitis and emphysema that the concept has become most well established.
Changes in Haem Synthesis Associated with Occupational Exposure to Organic and Inorganic Sulphides
Authors: Tenhunen R. , Savolainen H. , Jäppinen P.
Published: August 2015

1. Analysis of reticulocytes for δ-aminolaevulinic acid synthase (AmLev synthase, EC 2.3.1.37) and haem synthase (EC 4.99.1.1) activity in 17 workers in pulp production with low-level hydrogen sulphide and methylmercaptan exposure showed decreased activities in eight and six cases respectively.

2. Erythrocyte protoporphyrin concentration was below the control range in seven cases.

3. Low AmLev synthase and haem synthase activities were found in one patient with hydrogen sulphide intoxication 1 week after the event. The activities had returned to the control levels 2 months later, though erythrocyte protoporphyrin remained abnormally low.

4. In vitro, hydrogen sulphide inhibited haem synthase with an apparent Kl of 3.4 mmol/l. Sulphide anion, on the other hand, inhibited AmLev synthase activity 85% at 10 mmol/l concentration. Thiosulphate anion inhibited AmLev synthase activity 18% (Kl 27 mmol/l) and haem synthase activity 43% at 10 mmol/l concentration. Selenite inhibited AmLev synthase (Kl 5.1 mmol/l) and haem synthase (Kl 9.0 mmol/l).

5. The assay of AmLev synthase and haem synthase could be a valuable addition to the assessment of workers' health in industries generating hydrogen sulphide or/and methylmercaptan, although the mechanism of the toxic effect remains speculative.
Characterization of Pure Human Pancreatic Juice: Cobalamin Content, Cobalamin-Binding Proteins and Activity against Human R Binders of Various Secretions
Authors: Carmel Ralph , Abramson Stephan B. , Renner Ian G.
Published: August 2015

1. To clarify further the role of the pancreas in cobalamin absorption we characterized pure human pancreatic juice. With isolated exceptions, samples of the pure juice contained little cobalamin and had low cobalamin-binding capacities.

2. Ten of 13 specimens of pure human pancreatic juice collected in the cholecystokinin—pancreozymin phase were active against R binder from other sources and degraded them in vitro, as did four of ten secretin phase specimens. Moreover, enteropeptidase activated all but one of the inactive specimens. The sole refractory specimen was from a healthy volunteer. At the same time, the pure pancreatic juices from all three patients with pancreatic insufficiency were active against R binder, illustrating a surprising overlap in this property between healthy and abnormal subjects.

3. Trypsin, although active against R binder, did not fully account for the activity of pure human pancreatic juice, since aprotinin, which inhibited trypsin activity, inhibited the juice poorly. Furthermore, the activity of the juice did not always correlate with its trypsin activity. Chymotrypsin and elastase were active only at very high concentrations.

4. Pure human pancreatic juice affected salivary, gastric, biliary and endogenous pancreatic R binders in two ways. It converted them into a 70 000 mol. wt. molecule. It also produced what seemed to be small fragments and free cobalamin but which may have been primarily an easily dissociable binder—cobalamin bond. The former effect was particularly prominent when gastric R binder was the substrate, whereas saliva R binder seemed more susceptible to the second effect.

5. Holo-R binders were consistently much more resistant than apo-R binders to pure human pancreatic juice. The only exception was bile, whose holo- and apo-R binders appeared equally susceptible.

6. Our findings with pure human materials confirm that the pancreas degrades R binder. However, this activity seems intact in patients with pancreatic insufficiency, at least in vitro. The pancreatic role may be more important in destroying apo-R binder than in releasing cobalamin delivered to the intestine already bound to R binder. In addition, the ready liberation by pure human pancreatic juice of bound cobalamin in bile suggests that pancreatic juice is important in the hepatic recirculation of cobalamin.
Effect of Nicotinic Acid on Acylglycerol Metabolism in Human Adipose Tissue
Authors: Arner Peter , östman Jan
Published: August 2015

1. The effect of nicotinic acid on the metabolism of acylglycerols was investigated in human adipose tissue incubated with [U-14C]-glucose.

2. Nicotinic acid caused a 25% inhibition of the conversion of [U-14C]glucose into total lipids of adipose tissue, which was solely attributed to a decrease in the formation of the glycerideglycerol moiety of triacylglycerols. There was no effect on the conversion of [U-14C]glucose to carbon dioxide by nicotinic acid. The drug inhibited the rate of glycerol release by 50% and significantly reduced the tissue level of diacylglycerols but did not alter the tissue concentration of monoacylglycerols.

3. It is concluded that in human adipose tissue nicotinic acid inhibits both the synthesis and hydrolysis of triacylglycerols and influences the metabolism of diacylglycerols.
The Effect of Experimental Rat Tumours on Progesterone Binding in the Host Liver
Authors: Feuer G. , Kellen J. A.
Published: August 2015

1. The effect of the R3230 AC rat mammary adenocarcinoma on progesterone binding in the liver of female F344 rats has been studied. The growth of the transplanted tumour shows a positive correlation with increased binding of progesterone to the endoplasmic reticulum.

2. Both total binding rate and saturation level in the formation of specific progesterone microsomal receptor complex are increased.

3. This is paralleled by an elevated progesterone content of microsomal membranes.

4. in contrast, nonspecific progesterone binding in the microsomes is reduced. These results may represent a paraneoplastic change.
Tissue and Bacterial Splitting of Sulphasalazine
Authors: Khan A. K. Azad , Guthrie Glynis , Johnston H. H. , Truelove S. C. , Williamson D. H.
Published: August 2015

1. The cleavage of sulphasalazine at the azo bond by bacterial suspensions and tissue homogenates has been studied in vitro.

2. For maximum activity the azo reductase system requires anaerobic conditions and the presence of cofactors, namely NADPH and FAD. in this respect, sulphasalazine resembles other azo dyes.

3. Under optimum conditions all the species of bacteria tested were capable of splitting sulphasalazine and there were no major differences in the degree of activity shown by different species. The enzyme system is located within the bacterial cell and does not leak out of it.

4. All the tissues tested, both human and rat, showed azo reductase activity. The liver showed a much higher activity than the other tissues.
The Importance of the Renin-Angiotensin System in the Development and Maintenance of Hypertension in the Two-Kidney One-Clip Hypertensive Rat
Authors: Morton J. J. , Wallace Elisabeth C. H.
Published: August 2015

1. Blood pressure, renin concentration and angiotensin II were measured in unanaesthetized two-kidney one-clip hypertensive rats at 1 and 2 days, at weekly intervals up to 10 weeks and at 15 and 20 weeks after clipping.

2. Compared with values in sham-operated rats, renin and angiotensin II were initially increased at 1–2 days but were then suppressed between 2 and 4 weeks to levels similar to that found in sham-operated rats. Between 5 and 20 weeks renin and angiotensin II increased again to high levels.

3. There was a significant correlation between angiotensin II and blood pressure in acute rats 1–2 days after clipping (P < 0.05) and in chronic rats 8–20 weeks after clipping (P < 0.001). There was no difference in the slope of the regression lines but the regression line for the chronic rats was shifted upwards in a parallel manner.

4. The acute hypotensive response (−20.3 ± sd 24.9 mmHg) in 26 chronic rats given converting enzyme inhibitor was related to the basal renin and angiotensin II levels and followed the slope of the angiotensin II/blood pressure regression line for all chronic rats. Only one out of 26 rats reduced its blood pressure to normal levels.

5. In 12 rats at 4 weeks after clipping, when blood pressure was elevated but angiotensin II was suppressed, there was only a small fall in blood pressure (−7.1 ± sd 7.2 mmHg). This also followed the angiotensin II/blood pressure regression line for chronic rats but at the lower end. Blood pressure again was not reduced to normal.

6. These results suggest that renin and angiotensin II are increased up to 20 weeks after clipping, that there is no change in the net vascular responsiveness to endogenous angiotensin II at any stage in this experimental model and that the acute effect of angiotensin II is determined solely by its position in the same dose—response curve. Also with the exception of 1–2 days immediately after clipping the acute effect of angiotensin II plays only a minor, though variable, role in the hypertension and that some other mechanism, as yet undetermined, is of greater importance and begins to have an effect as early as 2 weeks after clipping.
The Effect of Insulin on the Rise in Blood Pressure and Plasma Aldosterone after Angiotensin II in Normal Man
Authors: Vierhapper H. , Waldhäusl W. , Nowotny P.
Published: August 2015

1. The effect of an intravenous infusion of insulin [2.5 units h−1 (m2 of body surface area)−1] on the rise in blood pressure and plasma aldosterone after intravenous angiotensin II (5, 10, and 20 ng min−1 kg−1) was investigated in six healthy, sodium-loaded men.

2. Serum insulin reached 96.8 ± 18.1 μ-units/ml (control: 7.0 ± 1.5 μ-units/ml) and serum potassium fell from 4.2 ± 0.2 mmol/l to 3.6 ± 0.2 mmol/l (P < 0.005).

3. Hyperinsulinaemia increased (P < 0.05) the secretion of aldosterone during the largest dose of angiotensin II (20 ng min−1 kg−1), but had no effect on the rise in blood pressure after angiotensin II.
Interaction of Diuretics and Non-Steroidal Anti-Inflammatory Drugs in Man
Authors: Favre L. , Glasson PH. , Riondel A. , Vallotton M. B.
Published: August 2015

1. The influence of four diuretics on renal prostaglandins was investigated in a study designed in two parts (A and B): A, 24 normal subjects on a constant sodium intake received frusemide (80 mg daily), or hydrochlorothiazide (100 mg), or triamterene (200 mg) or spironolactone (300 mg); B, the same subjects were pretreated for 3 days with indomethacin (150 mg daily), which was continued during the 3 day administration of the respective diuretics and during a 2 day post-diuretic period.

2. In study A, only triamterene provoked a rise in urinary prostaglandins E2 and F2α (+ 474 ± sem 92%, P < 0.01, and +192 ± 7%, P < 0.01). In study B, prostaglandins were significantly inhibited in all subjects. After indomethacin, the natriuretic effect of frusemide and spironolactone was reduced by 80 ± 12% (P < 0.01) and 54 ± 11% (P < 0.001), whereas the natriuresis induced by hydrochlorothiazide and triamterene was unchanged. No correlation was found between urinary PGE2 and F2α and natriuresis.

3. When triamterene was associated with indomethacin, two subjects developed reversible acute renal failure.

4. Plasma renin activity and urinary aldosterone were stimulated by the four diuretics in study A, but their response was blunted in study B. Urinary antidiuretic hormone was not modified by diuretics but was suppressed by indomethacin.

5. Diflunisal, a structurally unrelated non-steroidal anti-inflammatory drug, given to 12 of the subjects provoked similar interactions with frusemide, hydrochlorothiazide and spironolactone.

6. The results suggest that prostaglandins contribute to the natriuretic effects of frusemide and spironolactone, but not to those of hydrochlorothiazide and triamterene.
What Stimulates the Renin—Angiotensin System in Rats with two-Kidney Renal Hypertension?
Authors: Takata Y. , Doyle A. E. , Veroni M. , Duffy S. G.
Published: August 2015

1. Blood pressure, the hypotensive effect of captopril, plasma renin activity, renal renin content and kidney weight were measured in the two-kidney—one-clip model, the one-kidney—one-clip model and the two-kidney—one-clip model with the ureter of the contralateral kidney ligated in rats. The ureteric ligation was performed to abolish urinary excretion from the contralateral kidney in the two-kidney—one-clip model.

2. The development of hypertension after renal artery constriction was earlier and greater in the one-kidney—one-clip model and the two-kidney—one-clip model with ureter of the contralateral kidney ligated than in the two-kidney—one-clip model. A single oral dose of captopril produced a greater fall in blood pressure in both the two-kidney models than in the one-kidney—one-clip group.

3. Plasma renin activity and renal renin content of the clipped kidney were higher in the two-kidney model rats, whether or not the ureter had been ligated, than in the one-kidney—one-clip model animals, although more than half the rats from the two-kidney model had normal values. There was a significant correlation between plasma renin activity and the response to captopril in all groups, whereas in none of the three groups was the correlation between plasma renin activity and blood pressure significant.

4. The clipped kidney had a higher renin content than did the contralateral kidney, and the weight of the ischaemic kidney was decreased compared with the contralateral kidney whether it was untouched or had its ureter ligated. The weight of the clipped kidney was in the order one-kidney—one-clip model > two-kidney—one-clip model with ureter of the contralateral kidney ligated > two-kidney—one-clip model.

5. It was concluded that the renin-angiotensin system was stimulated to the similar degree in some animals for the two-kidney—one-clip models, whether or not the ureter of the contralateral kidney had been ligated, compared with the one-kidney—one-clip animals. This finding suggests that the contralateral kidney can stimulate renin secretion and synthesis in the clipped kidney independently of Na+ excretion.
A Study of Zinc Metabolism in Alcoholic Cirrhosis
Authors: Mills Peter R. , Fell Gordon S. , Bessent Rodney G. , Nelson Lesley M. , Russell Robin I.
Published: August 2015

1. Zinc metabolism was studied in 11 patients with alcoholic cirrhosis and 13 healthy volunteers using the isotope tracer 65Zn.

2. Intestinal absorption, whole-body content and total daily elimination of zinc were all increased in alcoholic cirrhosis, but the biological half-life of zinc did not differ from controls.

3. Hepatic zinc concentration was reduced in alcoholic cirrhosis and correlated with changes in hepatic alcohol dehydrogenase activity.

4. Patients with alcoholic cirrhosis in this study were not demonstrated to be zinc-deficient.
Response to Repeated Frusemide Administration on Low Chloride and Low Sodium Intake in the Rat
Authors: Kahn Thomas , Kaufman Allen M. , Mac-Moune Fernand L.
Published: August 2015

1. in animals on a normal NaCl intake despite the repeated administration of a diuretic Cl and Na excretion return to baseline values after initial Cl and Na loss. in order to delineate whether this apparent resistance is consequent primarily on a decreased effect of the diuretic, or compensatory Cl and Na reabsorption when the diuretic is not acting, rats were injected with frusemide (1.5 mg twice a day intraperitoneally for 4 days) while on diets differing in Cl and Na content.

2. On a normal NaCl diet Cl and Na excretion increased on day 1 and subsequently returned to baseline. On a low NaCl diet Cl and Na excretion remained above baseline on all 4 days, thereby demonstrating that frusemide continues to promote daily Cl and Na loss.

3. On a low Cl—normal Na intake Na excretion returned to baseline after day 1, while Cl excretion remained above baseline on all 4 days. The increase in K and net acid excretion was highest in these studies.

4. On a low Na—normal Cl intake Cl excretion returned to baseline after day 2, while Na excretion exceeded baseline on all 4 days. Daily K excretion increased least and net acid excretion decreased in these studies.

5. Hourly data on all four diets indicate that frusemide always has an acute effect to promote both Cl and Na excretion. in the recovery period Cl or Na reabsorption is enhanced when the respective ion is available. The apparent resistance to daily frusemide administration on a normal NaCl intake is primarily consequent on enhanced reabsorption balancing the chloriuretic and natriuretic effects. Daily changes in K and net acid excretion are also determined, in part, by these opposing effects.
Some Aspects of the Arterial Response to Venous Occlusion in Man
Authors: Ireland M. A. , Davies P. , Littler W. A.
Published: August 2015

1. Plethysmographic blood flow records made after venous occlusion of the forearm showed a biphasic response which was first vasodilator and then vasoconstrictor.

2. The myogenic nature of the vascoconstrictor phase was confirmed in eight subjects after total autonomic blockade with atropine, propranolol, phentolamine and guanethidine.

3. Forearm venous blood demonstrated a rise in hydrogen ion concentration and a fall in oxygen tension during venous occlusion, which may contribute to the vasodilatation phase.
Uptake of Inactive Renin by Human Ischaemic Kidney
Authors: McKenzie I. M. , Reisin E. , McKenzie J. K.
Published: August 2015

1. Plasma samples from both renal veins and infrarenal inferior vena cava were studied in 21 patients with unilateral renal artery stenosis and 11 patients without significant renal artery stenosis (essential hypertension), both groups being on unrestricted sodium intake.

2. Whether inactive renin was activated by acid or trypsin, it tended to be increased by 50–100% in unilateral renal ischaemia patients compared with essential hypertension. Active renin was increased two- to four-fold in unilateral renal ischaemia patients compared with those with essential hypertension. Thus the ratio of active to total renin in peripheral venous blood tended to be higher in unilateral renal ischaemia (0.37) than in essential hypertension (0.30) patients.

3. in renal vein blood from the affected kidney in unilateral renal ischaemia, the proportion of active renin to total renin was very high (68% for trypsinized samples and 73% for acidified samples). When affected renal vein blood was compared with infrarenal vena caval blood (equivalent to renal artery blood in amount and proportions of active and inactive renin), there was found to be a marked increase of active renin (ratio 2.83, significance of difference from 1.0, P < 0.001), as expected.

4. Inactive renin was decreased in affected renal vein blood compared with peripheral blood (ratio of renal vein to peripheral blood renin). This occurred whether acidification was used (ratio 0.62 ±0.11, P < 0.01) or trypsin (ratio 0.70 ± 0.13, P < 0.05).

5. The cause of the apparent uptake may be conversion of inactive renin into active renin by protease action in the ischaemic kidney. Urinary excretion or lymphatic drainage would seem unlikely.
Effect of Atrial Extract on Renal Function in the Rat
Authors: Pollock David M. , Banks Robert O.
Published: August 2015

1. The effects of myocardial extracts on renal function were studied in the rat. Infusion of rat atrial extract but not of ventricular extract resulted in a significant natriuresis in both pentobarbitone anaesthetized and unanaesthetized rats that were either deprived of food and water (for 18 h before the experiment) or were expanded with isotonic sodium chloride solution (1.5% body weight/h) during the experiment.

2. The increase in sodium excretion was three to four times greater in both groups of volume-expanded rats than in the two groups of food- and water-deprived rats.

3. Glomerular filtration rate and renal blood flow were not affected by atrial extract, indicating that the atrial natriuretic factor (ANF) directly inhibited sodium reabsorption at the tubular level.

4. Distal tubular blockade with a combination of frusemide and amiloride was employed to differentiate between proximal and distal tubular sites of action of ANF. Infusion of atrial extract into saline-expanded, distally blocked rats resulted in a transient increase in both the glomerular filtration rate and sodium excretion; fractional sodium excretion was unaffected by atrial extract in these experiments.

5. We conclude that (a) the renal response to ANF is not affected by pentobarbitone anaesthesia, (b) the renal response to ANF is dependent on the state of the extracellular fluid volume of the animal and (c) that ANF inhibits sodium reabsorption in the distal nephron.
Depressive Effect of Coughing on Spinal Monosynaptic Reflexes in Conscious Man
Authors: Maillard D. , Roby A. , Willer J. C.
Published: August 2015

1. The relationship between coughing and spinal monosynaptic reflexes (SMR) in extensors and flexors was investigated in eight healthy subjects by using the Hoffmann technique. Coughing exerted major depression (81% in extensor and 83% in flexor SMR). This depressant effect began simultaneously with the first cough and lasted through the coughing phase. Complete recovery to initial values occurred an average of 40 s thereafter.

2. in comparison, mental tasks induced only a slight decrease in SMR amplitude. in contrast, the Mueller and Valsalva manoeuvres induced facilitation.

3. During coughing, large variations in extensor amplitudes were observed that were coupled with the ventilatory cycle. Slight facilitation was observed during inspiration, but expiration induced pronounced depression, occurring 0.20 s after the beginning of the expiratory period. Experiments performed during baseline breathing failed to show any change throughout inspiratory or expiratory phases.

4. Chemical stimulation of irritant receptors (inhalation of citric acid) produced no specific modification of extensor responses compared with the effect of placebo inhalation (distilled water).

5. These data suggest that coughing exerts a major depressant effect on motor activity via a loop that possibly includes cardiopulmonary receptors and inhibitory supraspinal descending pathways.
Blood Pressure Response to Chronic Low-Dose Intrarenal Noradrenaline Infusion in Conscious Rats
Authors: Kleinjans J. C. S. , Smits J. F. M. , Kasbergen C. M. , Vervoort-Peters H. T. M. , Boudier H. A. J. Struyker
Published: August 2015

1. Sodium chloride solution (0.9%) or noradrenaline in doses of 4, 12 and 36 μgh−1 kg−1 was infused for five consecutive days, either intrarenally (by a new technique) or intravenously into rats with one kidney removed.

2. Intrarenal infusion of noradrenaline caused hypertension at doses which did not do so when infused intravenously.

3. Intrarenal compared with intravenous infusion of noradrenaline caused higher plasma noradrenaline concentrations and a shift of the plasma noradrenaline concentration-blood pressure effect curve towards lower plasma noradrenaline levels.

4. These results suggest that hypertension after chronic intrarenal noradrenaline infusion is produced by relatively higher levels of circulating noradrenaline and by triggering of an additional intrarenal pressor mechanism.
Immunoaffinity Chromatography of Canine High-Molecular-Weight Renin: Partial Purification and Characterization
Authors: Ikemoto Fumihiko , Dzau Victor J. , Haber Edgar , Takaori Kazuo , Yamamoto Kenjiro
Published: August 2015

1. Canine high-molecular-weight renin (mol. wt. 60 000) is believed to be a complex of renin (low-molecular-weight form, mol. wt. 40 000) and renin-binding substance. The immunocross-reactivity of high-molecular-weight renin and low-molecular-weight renin was demonstrated by using antibodies specific to low-molecular-weight renin.

2. Immunoaffinity chromatography with renin-specific antibodies coupled to Sepharose provided a simple and specific method for isolation of high-molecular-weight renin. High-molecular-weight renin with a specific activity of 137 600 ng of ANG I h−1 mg−1 of protein (19.6 Goldblatt units/mg of protein) was obtained.

3. This high-molecular-weight renin was stable in dithiothreitol (25 mmol/l), suggesting that disulphide bonds may not be involved in the binding mechanism between low-molecular-weight renin and renin-binding substance.

4. However, exposure to low pH (3.0) resulted in conversion of high-molecular-weight renin into the low-molecular-weight form.
Inhibitory Effects of ZK 36374, a Stable Prostacyclin Analogue, on Adhesion of Rabbit Platelets to Damaged Aorta and Serotonin Release by Adherent Platelets
Authors: Menys V. C. , Davies J. A.
Published: August 2015

1. The effects of ZK 36374, a prostacyclin analogue, were studied on adhesion of rabbit platelets to damaged rabbit aorta and on activation of platelets (judged by release of serotonin and formation of thromboxane-B2) in response to the processes of adhesion to the vessel surface and aggregation in response to microfibrillar collagen in suspension.

2. In the presence of ZK 36374 (10–100 nmol/l), platelet adhesion and fhromboxane-B2 formation were progressively reduced. The extent of serotonin release from adherent platelets was similar to that found for platelets aggregated with collagen. However, higher concentrations of ZK 36374 were required to inhibit serotonin release from adherent platelets than from aggregated platelets.

3. The results indicate that ZK 36374 acts similarly to native prostacyclin on adhesion and collagen-induced aggregation and unlike previously described analogues is equipotent.

4. The mechanism of release of serotonin induced by adhesion of platelets is less sensitive to the action of ZK 36374 than that of release induced by aggregation in response to microfibrillar collagen in suspension.
The Protective Effect of γ-Glutamyl l-Dopa on the Glycerol Treated Rat Model of Acute Renal Failure
Authors: Casson I. F. , Clayden D. A. , Cope G. F. , Lee M. R.
Published: August 2015

1. γ-Glutamyl l-dopa, a renal pro-drug for dopamine, was administered to rats before and after injection of glycerol, and to a control group which received water in place of glycerol. A third group of rats was given glycerol but no γ-glutamyl l-dopa.

2. The plasma creatinine in rats given γ-glutamyl l-dopa and glycerol was significantly lower than in rats receiving glycerol alone.

3. The fall in urine creatinine excretion, and polyuria, after glycerol was reduced by γ-glutamyl l-dopa and the natriuresis abolished.

4. γ-Glutamyl l-dopa given alone caused a 4000-fold increase in urine dopamine excretion, associated with a natriuresis.

5. The administration of γ-glutamyl l-dopa reduces the severity of renal failure produced by glycerol.
The Effects of Nutrition and Trauma on Whole-Body Protein Metabolism in Man
Authors: Clague M. B. , Keir M. J. , Wright P. D. , Johnston I. D. A.
Published: August 2015

1. Whole-body protein metabolism was determined by a primed constant-rate infusion of l-[l-14C]leucine in patients before and after elective surgery, the nutritional intake being carefully controlled and the surgical stress in individuals being assessed.

2. Pre-operatively, whole-body protein flux (P < 0.05) and synthesis (P < 0.05), along with amino acid oxidation (P < 0.01), increased with nutritional intake whereas protein breakdown remained unaltered. Whole-body protein balance also correlated with intake (P = 0.001).

3. Postoperatively, whole-body protein metabolism was determined with patients either fasted (group 1) or fed (group 2) and the change in metabolism in each individual from a pre-operative study, carried out in the fed state, was calculated. Whole-body protein breakdown increased in both groups (group 1, + 0.91 ±0.74 g day−1 kg−1; mean ± sd, n = 7: group 2, +0.47, +0.63 and +1.01 g day−1 kg−1n = 3), the change being significant in those fasted after surgery (P<0.05). However, the pattern of change in whole-body protein synthesis was entirely different in each group, rising in those fed throughout (+ 0.32, + 0.41 and + 0.66 g day−1kg−1n = 3) but falling in those fasted after surgery (−0.38, −0.80 and −1.33 g day−1kg−1n = 3). The changes in metabolism appeared more marked in those undergoing greatest surgical stress.

4. Some of the factors involved in the calculations are discussed and their effects on the overall conclusions are considered.

5. A concept of whole-body protein metabolism in the metabolic response to trauma is advocated whereby protein breakdown is largely obligatory to the response, whereas synthesis responds to substrate availability.
Release of Intracellular Enzymes from An Isolated Mammalian Skeletal Muscle Preparation
Authors: Jones D. A. , Jackson M. J. , Edwards R. H. T.
Published: August 2015

1. An isolated skeletal muscle preparation is described which has been used to study the efflux of enzymes in response to contractile activity, metabolic poisons and detergent treatment.

2. In both fast and slow muscles contractile activity caused a release of lactate dehydrogenase and creatine kinase that reached a peak 1–2 h after the end of stimulation. There was very little release during the 30 min stimulation period whether the muscles were under aerobic or hypoxic conditions.

3. Incubation of the muscles with cyanide and iodoacetate caused a similar delayed release of enzyme.

4. Disruption of cell membranes with detergent treatment caused an entirely different and very rapid pattern of enzyme release.

5. Enzyme release from the fatigued isolated muscle preparations appears to be initiated as a consequence of phosphorylcreatine or ATP depletion. The relevance of this to release of muscle enzymes after activity in vivo is discussed.
Propranolol Does Not Further Decrease the Clearance of Antipyrine in Patients with Alcoholic Cirrhosis
Authors: Larrey D. , Lebrec D. , Bercoff E. , Pessayre D.
Published: August 2015

1. We determined the clearance of antipyrine before, and during, the administration of propranolol in eight male patients with alcoholic cirrhosis and a recent episode of gastrointestinal bleeding.

2. The clearance of antipyrine in these patients was markedly reduced as compared with that in eight male, age-matched control subjects but was not further decreased after 1 month of propranolol administration.

3. Antipyrine is the prototype of a drug with a low hepatic clearance. We suggest that the hepatic metabolism of some low clearance drugs may not be further decreased when patients with alcoholic cirrhosis are placed on propranolol therapy for the prevention of recurrent gastrointestinal bleeding.
Evidence for Postjunctional Vascular α2-Adrenoceptors in Peripheral Vascular Regulation in Man
Authors: Elliott H. L. , Reid J. L.
Published: August 2015

1. Preliminary studies in healthy normotensive subjects with a selective α2−adrenoceptor antagonist 2 − {2 − (1,4 − benzodioxanyl)} − 2 − imidazoline (RX781094) in a dose of 0.2 μg/kg intravenously are described.

2. There was a transient increase in blood pressure, and plasma noradrenaline, 10–20 min after dosing and an associated reduction in heart rate. These observations are consistent with blockade of peripheral presynaptic α2−adrenoceptors in man.

3. The pressor responses to α−methylnoradrenaline, which has relatively selective agonist effects on α2−adrenoceptors, were markedly attenuated between 0.5 and 3.0 h after dosing (dose ratio > 20).

4. The pressor responsiveness to intravenous phenylephrine, a selective α1−adrenoceptor agonist, was only slightly reduced (dose ratio 1.7 ±0.8), as was the blood pressure rise after intravenous noradrenaline (dose ratio 1.7 ± 0.7).

5. The differential effects on the agonist pressor responses are consistent with antagonism by RX781094 of post−junctional α2−adrenoceptors on vascular smooth muscle.