bluuebunny/crossref_metadata_2025 huggingface dataset:
Hysteresis of the venous pressure-volume relationship in the forearm of borderline hypertensive subjects
Authors: Journo H. J. , Chanudet X. A. , Pannier B. M. , Laroque P. L. , London G. M. , Safar M. E.
Published: August 2015

1. The forearm venous pressure-volume relationship was studied in 14 young men with borderline hypertension and in 16 control subjects of the same age and sex. Strain-gauge plethysmography was used to evaluate volume changes after slow increases and decreases in distention, in order to estimate the amplitude of the hysteresis curve.

2. Compared with normotensive control subjects, subjects with borderline hypertension had significantly higher values of blood pressure, heart rate and forearm blood flow.

3. Baseline forearm venous tone was slightly, but not significantly, increased in borderline hypertensive subjects (21.35 ± 6.53 versus 18.75 ± 5.95 mmHg ml−1 100 ml−1) and was significantly enhanced after a cold pressor test. The increase was no higher in the borderline hypertensive subjects than in the normotensive control subjects.

4. The area of the hysteresis curve was significantly decreased (7.58 ± 3.58 versus 10.34 ± 5.67 arbitrary units; P = 0.0092) as was the extent of isotonic relaxation (creep) (0.28 ± 0.11 versus 0.39 ± 0.22 ml/100 ml; P = 0.0098) in borderline hypertensive subjects compared with control subjects. Both parameters were unaffected by the cold pressor test.

5. The study suggests that the viscous component of the venous wall is altered in young patients with borderline hypertension, indicating intrinsic changes in vascular segments which are not exposed to increased intraluminal pressure.
Vascular responses and ion exchange in diabetes: Authors' reply
Authors: Ritter J. M. , Viberti G. C.
Published: August 2015

1. Na+/Li+ countertransport is not a gold standard, or indeed any other kind of standard. It is a measure of the activity of one particular cation exchanger.

2. There is a large body of literature regarding the effects of oxidized low-density lipoprotein (LDL) in experimental animals and in vitro. Whether abnormal oxidized LDL or one of many other possible mechanisms underlies the inverse relationship that we observed between vascular sensitivity in vivo to nitroprusside or carbachol with erythrocyte Na+/Li+ countertransport in diabetic patients remains to be seen.

3. We caution against post hoc subgroup analysis (smokers versus non-smokers, low versus high plasma lipid levels, etc.) in studies of this size.
Variations in the glycoforms of serum α1-antichymotrypsin in liver diseases and after liver transplantation
Authors: Hachulla E. , Laine A. , Hedouin V. , Fournier C. , Maury F. , Mathieu C. , Pruvot F. R. , Declerck N. , Paris J. C. , Degand P.
Published: August 2015

1. Using crossed immunoaffinity electrophoresis with free concanavalin A in the first dimension, we studied the microheterogeneity of α1-antichymotrypsin due to various glycoforms in sera from patients with various liver diseases and after liver transplantation.

2. Studies by isoelectric focusing and immunoblotting and by crossed immunoelectrophoresis without concanavalin A in the first dimension allowed us to show that there is no dramatic variation in electrophoretic heterogeneity of α1-antichymotrypsin in the serum of patients with liver diseases or after liver transplantation when compared with that of normal subjects. Therefore the heterogeneity observed in crossed immunoaffinity electrophoresis is due to various interactions with concanavalin A.

3. The results were expressed as the ratio of concanavalin A non-reactive glycoforms plus concanavalin A weakly reactive glycoforms to concanavalin A reactive glycoforms, called Rα1-ACT. Rα1-ACT was significantly higher in patients with cirrhosis (n = 53) when compared with normal subjects (n = 30). The median Rα1-ACT was 1 (range 0.72–1.25) in normal subjects. It was 1.6 (range 1.18–3.02), 1.45 (range 0.65–4.12) and 2.24 (range 1.03–19) in cirrhosis of Child's grade A, B and C, respectively. There was a dramatic decrease in glycoforms with mostly biantennary glycans in some patients with Child's grade C cirrhosis. Serum levels of α1-antichymotrypsin were lower than normal only in some patients with Child's grade C cirrhosis.

4. Among the patients with acute viral hepatitis studied (n=17), five were studied longitudinally. Rα1-ACT increased after the peak level of serum transaminases and remained high while the level of serum transaminases decreased and liver regeneration occurred. In these patients there was no alteration in glycoforms with mostly biantennary glycans.

5. Four patients were studied after liver transplantation. During the first days after transplantation Rα1-ACT was low because of an increase in glycoforms with mostly biantennary glycans. After the first week, Rα1-ACT rose above the normal range because of an increase in glycoforms with pluriantennary glycans and it returned to normal within 3 post-operative weeks. Rα1-ACT remained high in a patient who presented with liver rejection.

6. The present study suggests that Rα1-ACT is a helpful additional marker for the evaluation of hepatocyte function.
Central bradykininergic system in normotensive and hypertensive rats
Authors: Alvarez Azucena L. , Delorenzi Alejandro , Santajuliana Daniel , Finkielman Samuel , Nahmod Victor E. , Pirola Carlos J.
Published: August 2015

1. The kinin antagonist des-Arg9−[Leu8]bradykinin, injected into the lateral ventricle, caused a long-lasting, dose-dependent reduction in arterial blood pressure and heart rate in spontaneously hypertensive rats but not in normotensive Wistar-Kyoto rats; the antagonist also blocked the pressor response to ventricularly infused bradykinin in both strains.

2. Bradykinin content was increased in the hypothalamus and septum and decreased in the dorsal medulla of spontaneously hypertensive rats when compared with those of normotensive Wistar-Kyoto rats, whereas similar bradykinin contents were observed in the pineal gland, hypophysis and rostroventrolateral medulla of both rat strains.

3. Increased concentrations of bradykinin and its precursor kininogen were found in the cerebrospinal fluid of spontaneously hypertensive rats.

4. Bradykinin receptor numbers, measured as the binding of [125I-Tyr1]bradykinin to nervous tissue, were found to be increased in the dorsal medulla and hypophysis, and to be decreased in the pineal gland, of spontaneously hypertensive rats.

5. Therefore, the central kinin system may participate, by both pre- and post-synaptic mechanisms, in the maintenance of hypertension in spontaneously hypertensive rats.
Acute metabolic and hormonal responses to the inhibition of lipolysis in non-obese patients with non-insulin-dependent (type 2) diabetes mellitus: effects of acipimox
Authors: Fulcher G. R. , Walker M. , Catalano C. , Farrer M. , Alberti K. G. M. M.
Published: August 2015

1. Increased rates of fatty acid oxidation are frequently observed in patients with non-insulin-dependent diabetes mellitus and may contribute to hyperglycaemia by both decreasing peripheral glucose disposal and, more importantly, by increasing the rate of gluconeogenesis and therefore hepatic glucose output. Despite this relationship between lipid and carbohydrate metabolism, fasting glucose concentrations do not fall acutely in patients with non-insulin-dependent diabetes mellitus when plasma non-esterified fatty acid concentrations and lipid oxidation rates are decreased, questioning the importance of this interaction to glycaemic control. We have therefore measured the acute changes that occur 120–150 min after administration of 500 mg of the anti-lipolytic agent acipimox in eight non-obese male patients with non-insulin-dependent diabetes mellitus.

2. After administration of acipimox, lipolysis was inhibited as reflected by lower plasma non-esterified fatty acid (0.05 ± 0.02 versus 0.55 ± 0.05 mmol/1, P < 0.001) and blood glycerol (8 ± 1 versus 56 ± 8 μmol/l, P < 0.001) concentrations. The lipid oxidation rate was decreased (0.63 ± 0.05 versus 1.02 ± 0.08 mg min−1 kg−1, P < 0.001), whereas there was a significant increase in the carbohydrate oxidation rate (1.93 ± 0.17 versus 1.22 ± 0.18 mg min−1 kg−1, P = 0.02). In addition, in the lipolysis-suppressed patients, there was a significant increase in serum cortisol (329 ± 47 versus 196 ± 43 nmol/l, P=0.03), serum growth hormone (5.44 ± 2.1 versus 0.6 ± 0.2 ng/ml, P=0.04), plasma glucagon (12 ± 2.5 versus 8.2 ± 2.0 ng min−1 ml−1, P = 0.005), plasma noradrenaline (1.82 ± 0.26 versus 1.39 ± 0.21 nmol/l, P=0.004) and adrenaline (0.32 ± 0.08 versus 0.20 ± 0.05 nmol/l, P=0.04) concentrations compared with control. Despite this marked hormonal response, there was no difference in hepatic glucose output, fasting blood glucose concentration or peripheral glucose disposal, although non-oxidative glucose disposal was less after acipimox (0.16 ± 0.16 versus 0.74 ± 0.20 mg min−1 kg−1, P=0.05).

3. We conclude that an acute decrease in fatty acid oxidation results in a switch to oxidation of glucose at the expense of glycogen stores, but apparently does not increase peripheral glucose uptake. Hepatic glucose output and fasting blood glucose concentration are maintained by an acute counter-regulatory response which presumably increases glycogen breakdown. Inhibitors of lipolysis and lipid oxidation are therefore more likely to lower fasting blood glucose concentration in the glycogen-depleted state.
Pernicious anaemia as a risk factor for osteoporosis
Authors: Eastell Richard , Vieira Nancy E. , Yergey Alfred L. , Wahner Heinz W. , Silverstein Murray N. , Kumar Rajiv , RIGGS B. Lawrence
Published: August 2015

1. If gastric acid is necessary for the absorption of dietary calcium, the total absence of gastric acid secretion that occurs in pernicious anaemia could result in bone loss. To investigate this, we measured calcium absorption and bone density in 21 postmenopausal women (ages 51–76 years) with pernicious anaemia and in 24 normal postmenopausal women (ages 51–79 years).

2. Relative to the normal women, in the women with pernicious anaemia the bone mineral density of the lumbar spine was decreased by 16% (P < 0.001).

3. After adjustment for age and body weight, lumbar spine bone mineral density correlated with the serum concentration of group 1 pepsinogens (a group of proteins produced by the gastric fundus) (r= 0.61, P < 0.01).

4. Despite achlorhydria, the women with pernicious anaemia had normal true fractional calcium absorption and normal serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D.

5. We conclude that gastric acid is not required for the absorption of dietary calcium. Thus, the loss of cancellous bone must be caused by some mechanism yet to be identified.
Polyunsaturated fatty acids suppress human peripheral blood lymphocyte proliferation and interleukin-2 production
Authors: Calder Philip C. , Newsholme Eric A.
Published: August 2015

1. The effects of a variety of fatty acids on human peripheral blood lymphocyte proliferation stimulated by concanavalin A or purified protein derivative of Mycobacterium tuberculosis were studied.

2. The proliferative response to concanavalin A was inhibited by all of the polyunsaturated fatty acids tested (eicosapentaenoate, arachidonate, docosahexaenoate, linoleate and α-linolenate) and also by the saturated fatty acid, stearate. The greatest inhibition of proliferation (approximately 85%) was caused by eicosapentaenoate.

3. The proliferative response to the purified protein derivative of Mycobacterium tuberculosis was inhibited by all of the polyunsaturated fatty acids tested, except α-linolenate, and also by stearate. The greatest inhibition of proliferation (approximately 75%) was caused by eicosapentaenoate.

4. The pattern of inhibition of proliferation by fatty acids was similar to that previously reported for rat lymphocytes with one exception: oleate did not inhibit human lymphocyte proliferation.

5. The proliferation of T-lymphocytes is dependent upon their ability to synthesize and secrete the cytokine, interleukin-2. In the presence of mitogen the concentration of interleukin-2 in the culture medium increased markedly above that in the medium of non-stimulated cells.

6. All polyunsaturated fatty acids tested caused a decrease in the concentration of interleukin-2; the greatest decrease (approximately 90%) was caused by eicosapentaenoate.

7. There was a good correlation between lymphocyte proliferation in the presence of fatty acids and interleukin-2 concentration. However, stearate did not decrease the interleukin-2 concentration but did inhibit lymphocyte proliferation.

8. These observations suggest that, although fatty acid suppression of interleukin-2 production may play a role in the inhibition of proliferation, it is not the sole mechanism by which fatty acids act.
Systemic and splanchnic haemodynamic effects of pentifylline in rats with portal hypertension
Authors: Dagenais M. , Pomier-Layrargues G. , Rocheleau B. , Giroux L. , Huet P.-M.
Published: August 2015

1. The systemic and splanchnic haemodynamic effects of pentifylline (40 mg/kg body weight intravenously) were assessed in rats with portal hypertension associated either with CCl4-induced cirrhosis (n= 13) or portal vein ligation (n=13).

2. Heparinized catheters were placed into the portal vein, inferior vena cava, aorta and left ventricle with exits from the neck. Haemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabelled microspheres and the reference sample method in seven rats in each group; portal-systemic shunting was measured using microsphere injection in the ileo-colic vein in six rats in each group.

3. Forty-five minutes after injection, pentifylline had no effect on mean arterial pressure, cardiac output, peripheral resistance, portal venous flow, hepatic artery flow or portal-systemic shunting in either group of rats with portal hypertension. The drug lowered portal pressure (−18%) in cirrhotic rats, but not in portal-vein-ligated rats.

4. These data demonstrate that pentifylline lowers portal pressure in cirrhotic rats without affecting portal venous flow and portal-systemic shunting; this effect is possibly mediated by changes in intrahepatic resistance related to the effects of pentifylline on blood viscosity and/or on intrahepatic vasomotor tone.
Differential responses in superior mesenteric artery blood flow may explain the variant pressor responses to clonidine in two groups with sympathetic denervation
Authors: Thomaides T. N. , Chaudhuri K. Ray , Maule S. , Mathias C. J.
Published: August 2015

1. Measurement of superior mesenteric artery blood flow along with systemic and regional haemodynamic changes in blood pressure, heart rate, cardiac index, forearm blood flow, digital skin blood flow and index finger temperature were made before and after administration of clonidine (2 μg/kg body weight intravenously) in 10 patients with multiple-system atrophy, 10 patients with pure autonomic failure and 15 age-matched healthy control subjects.

2. After clonidine, blood pressure fell in patients with multiple-system atrophy and control subjects but not in patients with pure autonomic failure.

3. Resting superior mesenteric artery blood flow was similar in patients with multiple-system atrophy and control subjects, but was higher in patients with pure autonomic failure. The fall in blood pressure after clonidine was accompanied by active dilatation of the superior mesenteric artery in patients with multiple-system atrophy and control subjects. This did not occur in patients with pure autonomic failure.

4. After clonidine, there was a fall in cardiac index in patients with multiple-system atrophy.

5. After clonidine, changes in other haemodynamic parameters were not significant in any group, except for a fall in forearm blood flow and a rise in index finger temperature in control subjects.

6. We conclude that after clonidine there are differential superior mesenteric artery blood flow responses in the two groups with autonomic failure (multiple-system atrophy and pure autonomic failure). These may relate to differences in the site of the sympathetic lesion, which is considered to be mainly central in multiple-system atrophy but peripheral in pure autonomic failure. The blood pressure responses to clonidine in the two groups may be largely dependent on changes in superior mesenteric artery blood flow.
Increased urinary excretion of prostaglandin E2 in patients with idiopathic hypercalciuria is a primary phenomenon
Authors: Henríquez-la Roche C. , Rodríguez-Iturbe B. , Parra G.
Published: August 2015

1. Urinary excretion of prostaglandin E2 is increased in patients with idiopathic hypercalciuria, but in order to conclude that hyperprostaglandinuria is a primary phenomenon, it must be demonstrated that high levels of urinary prostaglandin E2 can be dissociated from other factors, such as urine volume and natriuresis, and from the hypercalciuria itself.

2. We studied 10 patients with idiopathic hypercalciuria and 10 control subjects on high and low calcium diets providing daily calcium intakes of 30-35 mmol and 7.5-10 mmol, respectively, and similar sodium intakes. In addition, patients with idiopathic hypercalciuria and control subjects were studied during water restriction and water diuresis.

3. Urinary prostaglandin E2 excretion was more than twice as high in patients with idiopathic hypercalciuria than in control subjects on the low and high calcium diets as well as during water restriction and water diuresis (P<0.01).

4. Urinary prostaglandin E2 excretion was not affected by changes in urinary calcium excretion in patients with idiopathic hypercalciuria and in control subjects. Patients with idiopathic hypercalciuria on the low calcium diet and control subjects on the high calcium diet had similar levels of calciuria and natriuresis, yet urinary prostaglandin E2 excretion (mean ± SEM) was 11.62 ± 1.71 nmol/day in the patients with idiopathic hypercalciuria and 3.26 ± 0.48 nmol/day in the control subjects (P= 0.0006).

5. These results indicate that increased urinary prostaglandin E2 excretion is a cardinal characteristic of patients with idiopathic hypercalciuria.
Basal metabolic rate in adults with growth hormone deficiency and in patients with acromegaly: relationship with lean body mass, plasma insulin level and leucocyte sodium pump activity
Authors: Salomon Franco , Cuneo Ross C. , Hesp Richard , Morris Jenny F. , Poston Lucilla , Sönksen Peter H.
Published: August 2015

1. The relationship of lean body mass, plasma insulin concentration and leucocyte active sodium transport with basal metabolic rate was investigated in 24 adults with growth hormone deficiency before and after treatment with recombinant human growth hormone and in 10 patients with untreated acromegaly.

2. Based on total-body potassium determined by whole-body 40K counting, patients with acromegaly had increased lean body mass, whereas lack of growth hormone was associated with decreased lean body mass.

3. By indirect calorimetry, patients with acromegaly had increased basal metabolic rates and patients with growth hormone deficiency had decreased values when expressed as percentages of values predicted from the WHO/FAO/UNU equations. Basal metabolic rate expressed in terms of lean body mass was similar in acromegaly and growth hormone deficiency, but was higher than normal in both patient groups.

4. The leucocyte ouabain-sensitive sodium efflux rate constant was decreased in both patients with acromegaly and patients with growth hormone deficiency, and there was no correlation with basal energy expenditure, fasting plasma insulin level or serum growth hormone level.

5. There was no increase in the sodium efflux rate constant in patients with growth hormone deficiency after 1 month on treatment with recombinant human growth hormone.

6. Apparent differences in basal metabolic rate in growth hormone deficiency and acromegaly are due to changes in lean body mass. Both adults with growth hormone deficiency and patients with acromegaly have increased energy expenditure, probably owing to changes in fuel metabolism which are not reflected in the leucocyte sodium pump activity.
Role of kinins in pain and hyperalgesia: psychophysical studies in a patient with kininogen deficiency
Authors: Raja Srinivasa N. , Campbell James N. , Meyer Richard A. , Colman Robert W.
Published: August 2015

1. Bradykinin is considered to be an important mediator of pain and hyperalgesia associated with injury and inflammation. Psychophysical studies were conducted in a patient with complete kininogen deficiency to determine whether the absence of bradykinin was associated with abnormalities in pain sensibility. Pain evoked by heat stimuli to the thenar eminence was tested before and after a localized burn, which has been shown to cause hyperalgesia in normal subjects. In addition, pain evoked by intradermal administration of bradykinin (0.1–10 μg) to the forearm and the effects of bradykinin on pain induced by heat stimuli were studied. The patient rated the intensity of pain evoked by all heat stimuli relative to the pain induced by a 3s 45°C stimulus.

2. The patient's heat pain threshold (45°C) in the glabrous skin was similar to that of age-matched control subjects (n = 5) and to that previously observed in younger control subjects.

3. The burn resulted in a decrease in pain threshold and an increase in pain induced by suprathreshold stimuli. The magnitude of hyperalgesia was within the range observed in the age-matched control subjects and in younger control subjects. Thus, kinins are not essential for the development of hyperalgesia after heat injury.

4. In control subjects, intradermal injections of bradykinin produced pain and hyperalgesia to heat stimuli. In the patient, intradermal bradykinin injections induced minimal pain and no hyperalgesia to heat stimuli. Thus, congenital absence of kininogens may be associated with a deficiency in bradykinin receptors.
Nyctohemeral changes in bone turnover assessed by serum bone Gla-protein concentration and urinary deoxypyridinoline excretion: effects of growth and ageing
Authors: Eastell Richard , Simmons Patricia S. , Colwell Antony , Assiri Adel M. A. , Burritt Mary F. , Graham R. , Russell G. , Riggs B. Lawrence
Published: August 2015

1. To investigate whether there is a nyctohemeral rhythm in bone turnover, we measured serum bone Gla-protein (osteocalcin, an index of osteoblast activity) concentration every 2 h and urinary deoxypyridinoline (a marker of bone collagen resorption) excretion for 8 h periods in 10 pubertal girls (aged 10–14 years), 15 premenopausal women (aged 20–49 years) and 17 postmenopausal women (aged 50–75 years).

2. The serum concentration of bone Gla-protein and the urinary excretion of deoxypyridinoline were five times higher in the pubertal girls than in the premenopausal women. The urinary excretion of deoxypyridinoline in the postmenopausal women was twice that in the premenopausal women.

3. There was a nyctohemeral pattern in all age groups with mean night-time increases of 28% (P<0.001) in the urinary excretion of deoxypyridinoline and of 5% (P<0.001) in the serum bone Gla-protein concentration.

4. There also were nyctohemeral patterns in the urinary excretion of calcium (P<0.02), sodium (P<0.001) and potassium (P<0.001), with decreases at night. There was a negative correlation between the night-time changes in the urinary excretion of deoxypyridinoline and calcium, especially in adult women (P<0.01).

5. The serum level of parathyroid hormone increased with age, but this effect was only observed at night (01.00 to 07.00 hours). There was a nyctohemeral rhythm of the serum intact parathyroid hormone level at all ages, with a peak in the afternoon and night.

6. Thus, at night, there is a large increase in bone resorption and a small increase in osteoblastic activity, representing a nyctohemeral rhythm of bone turnover. Although the amplitudes of bone formation and bone resorption are greater during growth, the pattern of nyctohemeral changes present during growth continues up to the age of 75 years.
Spontaneous release of interleukin-1 and interleukin-6 by peripheral blood mononuclear cells after oophorectomy
Authors: Pioli Giulio , Basini Guiseppina , Pedrazzoni Mario , Musetti Giovanni , Ulietti Vittorio , Bresciani Donatella , Villa Paola , Bacchi Alberto , Hughe David , Russell Graham , Passeri Mario
Published: August 2015

1. We studied the changes in interleukin-1 and interleukin-6 secretion by peripheral blood mononuclear cells from 12 premenopausal women after oophorectomy and seven premenopausal women who had undergone simple hysterectomy.

2. The results showed that 1 month after surgery interleukin-1 secretion increased by 414 ± 171% (mean ± sem) and interleukin-6 secretion increased by 1354 ± 481% in oophorectomized women, whereas only non-significant fluctuations in the secretion of both cytokines (−9% ± 29% for interleukin-1 and −31% ± 19% for interleukin-6) were seen in the women who had undergone simple hysterectomy. The difference between the two groups was significant (P= 0.035 for interleukin-1 and P = 0.003 for interleukin-6). In addition, oophorectomy, but not simple hysterectomy, was followed by significant increases in plasma ionized calcium concentration (P<0.05), plasma alkaline phosphatase activity (P<0.01) and plasma osteocalcin concentration (P<0.02), and a reduction in plasma parathyroid hormone level (P<0.01).

3. We conclude that ovary ablation may modify cytokine secretion by peripheral blood mononuclear cells. If this phenomenon occurs in the bone micro-environment, it could be important in the loss of bone observed after oophorectomy. However, the possibility of an independent alteration induced by the lack of gonadal hormones but unrelated to bone turnover cannot be excluded.
Effects of the angiotensin II receptor antagonist Losartan (DuP 753/MK 954) on arterial blood pressure, heart rate, plasma concentrations of angiotensin II and renin and the pressor response to infused angiotensin II in the salt-deplete dog
Authors: MacFadyen R. J. , Tree M. , Lever A. F. , Reid J. L.
Published: August 2015

1. The blood pressure, heart rate, hormonal and pressor responses to constant rate infusion of various doses of the angiotensin (type 1) receptor antagonist Losartan (DuP 753/MK 954) were studied in the conscious salt-deplete dog.

2. Doses in the range 0.1–3 μmin−1 kg−1 caused no change in blood pressure, heart rate or pressor response to angiotensin II (54 ng min−1kg−1), and a dose of 10 μgmin−1 kg−1 had no effect on blood pressure, but caused a small fall in the pressor response to angiotensin II. Infusion of Losartan at 30 μmin−1 kg−1 for 3 h caused a fall in mean blood arterial pressure from baseline (110.9 ± 11.2 to 95.0 ± 12.8 mmHg) and a rise in heart rate (from 84.6 ± 15.1 to 103 ± 15.2 beats/min). Baseline plasma angiotensin II (42.5 ± 11.8 pg/ml) and renin (64.5 ± 92.7 μ-units/ml) concentrations were already elevated in response to salt depletion and rose significantly after Losartan infusion to reach a plateau by 70 min. The rise in mean arterial blood pressure after a test infusion of angiotensin II (35.3 ± 11.6 mmHg) was reduced at 15 min (11.8 ± 6.8 mmHg) by Losartan and fell progressively with continued infusion (3 h, 4.3 ± 3.3 mmHg). The peak plasma angiotensin II concentration during infusion of angiotensin II was unaffected by Losartan, but the rise in plasma angiotensin II concentration during infusion was reduced because of the elevated background concentration. Noradrenaline infusion caused a dose-related rise in mean blood arterial pressure (1000 ngmin−1kg−1, +19.9 ± 8 mmHg; 2000ngmin−1 kg−1, +52.8 ± 13.9 mmHg) with a fall in heart rate (1000 ng min−1 kg−1, −27.9 ± 11.5 beats/min; 2000 ng min−1 kg−1, −31.2 ± 17.3 beats/min). During Losartan infusion the 1000 but not the 2000 ng min−1 kg−1 noradrenaline infusion caused a greater rise in mean arterial blood pressure and a greater fall in heart rate. The fall in heart rate tended to decrease with continued infusion of Losartan. Plasma catecholamine concentrations were unaffected by Losartan. In a further study, higher doses of Losartan (100, 300 and 1000 μg min−1 kg−1; 30 min) produced greater falls in mean arterial blood pressure also with a rise in heart rate and complete blockade of the pressor effect of infused angiotensin II. Some animals became disturbed at the highest dose. 3. Losartan produces rapid dose-related falls in blood pressure and a rise in heart rate and renin release with elevation of plasma angiotensin II. Pressor responses to angiotensin II are reduced at intermediate doses and are eliminated at high doses. Losartan does not appear to inhibit angiotensin II clearance from the plasma and may in some way increase it.
Effects of acute NaCl, KCl and KHCO3 loads on renal electrolyte excretion in humans
Authors: van Buren Marjolijn , Rabelink Ton J. , van Rijn Herman J. M. , Koomans Hein A.
Published: August 2015

1. Potassium salts increase sodium excretion in humans. To define the role of the potassium ion in this effect, we compared the effects of equimolar single oral loads of 100 mmol of NaCl and KCl on renal electrolyte excretion in seven healthy subjects. In a second group (n = 7), we infused equimolar loads of NaCl or KCl (0.75 mmol/kg in 2 h).

2. In both experiments the KCl load quickly increased plasma potassium and aldosterone concentrations and potassium and sodium excretion to a maximum by 2 h after the load, whereas the NaCl load had no such effect.

3. In a third group (n = 7) we compared the effects of single oral loads of KCl and KHCO3 (1 mmol/kg), to assess the role of the anion in the natriuretic effect of potassium salts.

4. KCl and KHCO3 transiently stimulated urinary excretion of potassium and sodium in an identical manner.

5. We also followed the changes in acid excretion over time. Whereas both KCl and KHCO3 loading decreased acid excretion, this effect was greater after KHCO3 loading. Interestingly, acid excretion did not decrease further after the first collection hour after the potassium load, although the plasma potassium concentration was still increasing.

6. From these data we conclude (1) that increased excretion of sodium, potassium and chloride and decreased excretion of protons after administration of potassium salts are the specific effects of the potassium component; (2) that potassium also appears to have secondary, indirect effects on proton excretion, the mechanism of which remains to be clarified.
Effect of chronic hypoxia on rat pulmonary resistance vessels: vasodilatation by atrial natriuretic peptide
Authors: Rogers T. K. , Stewart A. G. , Morice A. H.
Published: August 2015

1. We have investigated the vasoreactivity of isolated pulmonary resistance vessels of rats after acclimatization to chronic hypoxia in a normobaric, hypoxic chamber. Vasoconstriction, in response to KCl and prostaglandin F2α, and vasodilatation, in response to atrial natriuretic peptide, were studied isometrically in a small-vessel myograph. Resting tensions were set to simulate transmural pressures of 17.5 mmHg or 35 mmHg.

2. There were no significant differences between intergroup internal vessel diameters or maximal contractile responses to either agonist. Both control and chronically hypoxic vessels generated significantly greater active contractions at 35 mmHg than at 17.5 mmHg. There were significant positive correlations between vessel diameter and maximum contractility for both control and chronically hypoxic vessels, but when contraction was expressed as equivalent transmural pressure no correlation existed.

3. There was a significant increase in potency (as measured by the concentration necessary to produce 50% of the maximum response) of KCl in chronically hypoxic vessels compared with control vessels at 35 mmHg, but not at 17.5 mmHg. In contrast, the potency of prostaglandin F2α was significantly increased in chronically hypoxic vessels at 17.5 mmHg, but not at 35 mmHg. Thus the change in contractile responses of vessels from chronically hypoxic animals, in terms of maximal response and potency, is dependent on both resting pressure and agonist used.

4. After exposure to chronic hypoxia, atrial natriuretic peptide induced significantly greater maximal relaxation of pulmonary resistance vessels at both resting pressures, but its potency was unaffected.
Stimulatory action of parathyroid hormone on renin secretion in vitro: a study using isolated rat kidney, isolated rabbit glomeruli and superfused dispersed rat juxtaglomerular cells
Authors: Saussine Christian , Judes C. , Massfelder T. , Musso M.-J. , Simeoni U. , Hannedouche T. , Helwig J.-J.
Published: August 2015

1. We have previously reported that pharmacological concentrations (125 nmol/l) of parathyroid hormone may stimulate renin release in the stable recirculating and non-filtering isolated rat kidney.

2. In the present study we have attempted to extend these initial observations by examining the concentration-related response of renin release to parathyroid hormone, using the same model of isolated kidney, and determining whether the effect of parathyroid hormone on renin release can be demonstrated by more direct approaches. Thus, the effects of parathyroid hormone on renin secretion were investigated in two other renal preparations: isolated rabbit glomeruli and isolated rat juxtaglomerular cells.

3. In the isolated kidney, rat parathyroid hormone significantly stimulated renin accumulation in the perfusate in a concentration-related manner with a threshold of 1 nmol/l.

4. In both glomeruli and juxtaglomerular cells bovine [Nle8,18,Tyr34]parathyroid hormone-(1–34)amide effectively and repeatedly stimulated renin release. These results imply that there is a direct stimulatory effect of parathyroid hormone on renin release.

5. We also examined the effect of [Nle8,18, Tyr34]parathyroid hormone-(l-34)amide during extracellular calcium buffering in the glomeruli. [Nle8,18,Tyr34]parathyroid hormone-(1–34)amide was uneffective in calcium-free medium. Increasing the extracellular ionized calcium concentration to 2.5 mmol/l increased the extent of stimulation in accordance with the reported ability of parathyroid hormone to block calcium channels and relax vascular smooth muscle cells.

6. These results provide further support for the role of parathyroid hormone as a direct mediator of renin secretion; moreover, the renin-stimulating action of parathyroid hormone may be mediated through the inhibition of calcium influx.s
Effect of respiratory acidosis and alkalosis on plasma catecholamine concentrations in anaesthetized man
Authors: Low J. M. , Gin T. , Lee T. W. , Fung K.
Published: August 2015

1. Plasma concentrations of noradrenaline and adrenaline were measured in 11 anaesthetized patients during normocapnia, hypocapnia and hypercapnia. Hypocapnia was produced by deliberate hyperventilation and hypercapnia by adding carbon dioxide to the inspired gas mixture.

2. With a median (range) arterial partial pressure of carbon dioxide of 4.7 (4.2–5.2) kPa, the median (range) plasma concentration of noradrenaline was 0.41 (0.12–0.94) nmol/l and of adrenaline was 0.15 (0.05–0.31) nmol/l.

3. With an arterial partial pressure of carbon dioxide of 2.6 (2.2–3.3) kPa, there was no change in the plasma concentration of noradrenaline [0.37 (0.12–0.86) nmol/l] or that of adrenaline [0.16 (0.05–0.32) nmol/l].

4. However, with an arterial partial pressure of carbon dioxide of 10.4 (7.6–13.2) kPa, there were significant increases in the plasma concentrations of both noradrenaline [1.13 (0.79–2.05) nmol/l, P < 0.01] and adrenaline [0.67 (0.20–2.92) nmol/l, P < 0.05].

5. This is the first demonstration in man that respiratory acidosis causes an increase in plasma concentrations of catecholamines.
Studies of human zinc kinetics using the stable isotope 70Zn
Authors: Lowe N. M. , Green A. , Rhodes J. M. , Lombard M. , Jalan R. , Jackson M. J.
Published: August 2015

1. The short-term (120 min) kinetics of Zn turnover has been studied in control subjects and patients with alcoholic liver disease after intravenous injection of 0.5 mg of 96.5% enriched 70ZnCl2.

2. The 70Zn enrichment of plasma was found closely to obey two-compartment kinetics and the derived two-component decay equation has been used to calculate the size and turnover of the initial two rapidly exchanging pools of body Zn.

3. In normal subjects isotopic Zn appears initially to equilibrate with the whole of the plasma Zn which comprises the first metabolic compartment, pool a. This has a size of 0.72 ± 0.1 μmol/kg. 70Zn equilibration then occurs with a second compartment, pool b, consistent with a rapidly exchanging liver Zn pool of size 3.60 ± 0.93 μmol/kg. The fractional turnover rate of pool b was found to be fivefold slower than that of pool a.

4. In the alcoholic group an expansion of pool a was observed (1.63 ± 0.39 μmol/kg), but the size of the second pool was not significantly different from that of control subjects (5.55 ± 1.0 μmol/kg), although its fractional turnover was significantly increased (Kab: control subjects, 0.018 ± 0.002 min−1, alcoholic patients, 0.031 ± 0.006 min−1).

5. These data therefore demonstrate that kinetic studies using stable isotopes of Zn can provide novel information on exchangeable Zn pools in man, but provide no support for the possibility of an underlying Zn depletion in patients with alcoholic liver disease.
Renal renin activity is associated with alterations of the renin gene in recombinant inbred rat strains
Authors: Pohlová Irena , Zicha Josef , Křen Vladimir , Kuneš Jaroslav , Pravenec Michal
Published: August 2015

1. A structural alteration within the first intron of the renin gene in spontaneously hypertensive rats was demonstrated to co-segregate with blood pressure in some sets of F2 hybrids or recombinant inbred strains. There is no evidence as to whether restriction fragment length polymorphism of the renin gene is associated with any of the changes in the renin tissue level. For this reason we have determined renal renin activity in spontaneously hypertensive, Wistar-Kyoto and Brown Norway rats as well as in 22 recombinant inbred strains derived from F2 hybrids of spontaneously hypertensive and Brown Norway rats.

2. At the age of 4 months significantly lower renal renin activity was observed in spontaneously hypertensive rats than in both normotensive rat strains, Wistar-Kyoto and Brown Norway. The presence of the spontaneously hypertensive rat allele in recombinant inbred strains was associated with a substantially lower renal renin activity as compared with recombinant inbred strains bearing the Brown Norway rat allele. There was no relationship between renal renin activity and the polymorphism in either the angiotensinogen gene or the angiotensin-converting enzyme gene.

3. There was a borderline correlation between blood pressure and renal renin activity in recombinant inbred strains. Nevertheless, additional comparisons within recombinant inbred strains bearing the spontaneously hypertensive rat allele of the renin gene failed to reveal any significant relationship between blood pressure level and renal renin activity.

4. Our data suggest that the restriction fragment length polymorphism marking the renin gene of the spontaneously hypertensive rat is accompanied by an alteration in the renin-angiotensin system at the renal level. The mechanisms by which structural abnormalities of the renin gene might influence the renin level in the kidney remain to be investigated.
Lithium clearance method and the renal response to low-dose dopamine in man: a randomized, controlled study
Authors: Olsen Niels Vidiendal , Olsen Michael Hecht , Fogh-Andersen Niels , Feldt-Rasmussen Bo , Kamper Annelise , Plum Inger , Strandgaard Svend , Leyssac Paul Peter
Published: August 2015

1. The effect of a single dose of lithium on renal function before and during intravenous infusion of dopamine (3 μg min−1 kg−1) was investigated in 12 healthy males. In a double-blind and randomized design, 450 mg or 600 mg of lithium carbonate or placebo was administered orally at 22.00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1 h baseline period and three 1 h periods during dopamine infusion.

2. Baseline sodium clearance with placebo was 0.65 ± 0.35 ml/min, but with lithium it increased to 1.25 ± 0.44 (P < 0.001) and 1.17 ± 0.46 ml/min (P < 0.01) after 450 and 600 mg, respectively. Urine flow rates were unchanged compared with placebo. Lithium did not significantly affect glomerular filtration rate, but both doses slightly increased effective renal plasma flow by 7% (P < 0.05) and 10% (P < 0.01), respectively.

3. The maximal natriuretic and diuretic effects of dopamine were not reduced by lithium, but the percentage increases in sodium clearance were significantly diminished after 450 mg (P < 0.01) and 600 mg (P < 0.001) of lithium. Lithium had no effect on dopamine-induced changes in effective renal plasma flow, glomerular filtration rate or osmolal clearance. Neither lithium nor dopamine influenced plasma concentrations of renin, aldosterone or atrial natriuretic peptide.

4. In conclusion, single test doses of lithium, as normally used in lithium clearance studies, increase baseline values of sodium clearance and effective renal plasma flow. Although these effects of lithium do not reduce the maximal renal responses to low-dose dopamine, they result in an underestimation of the percentage increase in sodium excretion.
Possible long-lasting inhibition of converting enzyme by enalapril in human cerebrospinal fluid
Authors: Fanciullacci Marcello , Alessandri Massimo , Nicolodi Maria , Michelacci Sergio , Sicuteri Federigo
Published: August 2015

1. Converting enzyme and neutral endopeptidase activities were both measured every 3 h by a fluorimetric method in plasma and cerebrospinal fluid of patients diagnosed as migraineurs with aura after lumbar puncture, which was performed 9 h after an acute oral dose of enalapril or placebo.

2. A reduced converting enzyme activity, as compared with placebo, was observed in patients who were given enalapril. On the other hand, neutral endopeptidase activity detected after enalapril did not differ from that measured after placebo.

3. The results seem to indicate that enalapril penetrates the blood-brain barrier in sufficient amounts to reduce converting enzyme activity. Moreover, neutral endopeptidase was not affected by enalapril. Therefore, those clinical effects of the drug which have been attributed to the involvement of central opioid mechanisms may depend on the inhibition of brain converting enzyme but not the inhibition of brain neutral endopeptidase.
Ultrastructural Characterization of Platelet-Activating Factor-Stimulated Human Eosinophils from Patients with Asthma
Authors: Kroegel Claus , Dewar Ann , Yukawa Tatsuo , Venge Per , Barnes Peter J. , Chung K. Fan
Published: August 2015

1. Purified human eosinophils from asthmatic patients were stimulated with platelet-activating factor in vitro and examined for morphological changes by transmission electron and light microscopy. Changes were also evaluated by morphometric analysis and were related to the platelet-activating factor-stimulated release of granular eosinophil cationic protein.

2. Stimulation of eosinophils with platelet-activating factor induced a dose-dependent shape change, including the elongation of cells, loss of microvilli and the formation of lamellipodia. This effect was maximal at 25 min and was reversible.

3. Stimulation with platelet-activating factor also induced granule movement to the cell periphery and fusion of adjacent granules. Granules became swollen and vesiculated, whereas both the matrix and core showed evidence of solubilization.

4. There was a time-dependent secretion of eosinophilic cationic protein from human eosinophils upon stimulation with platelet-activating factor which occurred without significant lactate dehydrogenase release.

5. Morphometric analysis of the transmission electron micrographs indicated a significant reduction in cytoplasmic area after 10 min of incubation with platelet-activating factor from 39.0 ± 1.7 μm2 for untreated eosinophils to 33.2 ± 2.3 μm2 (P < 0.02) for platelet-activating factor-treated cells, underscoring the observation that the cells change from spherical to ellipsoidal. No significant increase in the perimeter of the cells was found.

6. The number of granule-profiles in platelet-activating factor-stimulated eosinophils was slightly reduced when compared with control, and an increase in granule area was observed 10 min after platelet-activating factor challenge (0.215 ± 0.011 μm2 versus 0.246 ± 0.016 μm2).

7. Human eosinophils from patients with asthma stimulated with platelet-activating factor undergo both cellular and granular alterations and reorganization which parallel the release of granular eosinophil basic protein.
Somatostatin as a Modulator of Distal Nephron Water Permeability
Authors: Ray Cheryl , Carney Shane , Morgan Trefor , Gillies Alastair
Published: August 2015

1. Experiments in vivo and in vitro were performed in the rat to define the role of somatostatin in modulating the hydro-osmotic action of arginine vasopressin.

2. Somatostatin had a biphasic effect on basal collecting duct diffusional water permeability with 10−9 mol/l somatostatin producing a 14% reduction in permeability, whereas concentrations of 10−6 and 10−5 mol/l significantly increased basal water permeability by 13% and 22%, respectively. Somatostatin (10−9 mol/l) also inhibited the increase in water permeability produced by arginine vasopressin, although this inhibitory effect was reduced by a 10-fold increase in arginine vasopressin concentration (5 ng/ml).

3. In the anaesthetized water-diuretic rat, low dose somatostatin (60 μg/h) increased free water clearance by 23% (P < 0.01), whereas increasing the somatostatin concentration (600 μg/h) produced a transitory 40% fall in free water clearance (P < 0.01). As in the experiment in vitro, somatostatin inhibited the action of arginine vasopressin, although a very high concentration of arginine vasopressin (250 ng/h) partly overcame this effect.

4. Glomerular filtration rate and renal electrolyte excretion (sodium, potassium, calcium, magnesium) were not altered by somatostatin, although renal inorganic phosphate excretion was increased. The papillary solute gradient was unaltered by somatostatin.

5. These results suggest that circulating somatostatin may have a physiological role in modulating distal nephron water transport with a low concentration directly inhibiting and a high concentration facilitating water transport. There is also evidence of competitive binding between somatostatin and arginine vasopressin which antagonizes the hydro-osmotic action of arginine vasopressin.