bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in the effects of angiotensin converting enzyme inhibitors with or without a thiol group in chronic renal failure in rats
Authors: Ohishi Akira , Suzuki Hiromichi , Nakamoto Hidetomo , Katsumata Hiroshige , Sakaguchi Hiroshi , Saruta Takao
Published: August 2015

1. We have investigated the effects of the non-renin-mediated actions of angiotensin converting enzyme inhibitors on the progression of chronic renal failure accelerated by hypertension. For this purpose, we studied the effects of captopril (a thiol-containing angiotensin converting enzyme inhibitor), enalapril (an angiotensin converting enzyme inhibitor without a thiol group) and cysteine (a thiol-containing amino acid which has no angiotensin converting enzyme-inhibitory action) in adriamycin-treated rats with deoxycorticosterone acetate-salt hypertension, in which the renin-angiotensin system was suppressed.

2. There were no significant differences in blood pressure between these groups and the control group [adriamycin-treated group with deoxycorticosterone acetate-salt loading, 206 ± 7 mmHg (27.4 ± 0.9 kPa) at week 10].

3. Massive proteinuria occurred in all groups. At the end of the experiment (at week 10), urinary protein excretion was significantly reduced in the captopril and cysteine groups compared with the control group. No manifest improvements appeared in the enalapril group.

4. Levels of serum creatinine and blood urea nitrogen increased progressively. At week 10, the increases in the serum levels of creatinine were less in the captopril (87 ± 16 mmol/l) and cysteine (80 ± 19 mmol/l) groups than in the control group (124 ± 27 mmol/l) (P < 0.01). No marked differences were found between the control and enalapril groups.

5. Captopril and cysteine caused more than a threefold reduction in the focal glomerulosclerosis score when compared with that in the control group, but enalapril did not decrease the score. The extent of tubulo-interstitial change was parallel with the focal glomerulosclerosis score.

6. We conclude that the thiol group is possibly involved in the mechanism of the beneficial effects of some angiotensin converting enzyme inhibitors on the progression of chronic renal failure exacerbated by hypertension.
Intestinal glucose transport using perfused rat jejunum in vivo: model analysis and derivation of corrected kinetic constants
Authors: Meddings Jonathan B. , Westergaard Henrik
Published: August 2015

1. The transport model that best describes intestinal glucose transport in vivo remains unsettled. Three models have been proposed: (1) a single carrier, (2) a single carrier plus passive diffusion, and (3) a two-carrier system. The objectives of the current studies were to define the transport model that best fits experimental data and to devise methods to obtain the kinetic constants, corrected for diffusion barrier resistance, with this model.

2. Intestinal glucose uptake was measured during perfusion of rat jejunum in vivo over a wide range of perfusate concentrations and diffusion barrier resistance was determined under identical experimental conditions. The data were fitted to the transport equations that describe the three models with appropriate diffusion barrier corrections, and the kinetic constants were derived by non-linear regression techniques. The fit of each model to the data was assessed using six statistical tests, five of which favoured a model described by a single carrier and passive diffusion.

3. The main conclusions of these studies are: (1) kinetic constants uncorrected for diffusion barrier resistance are seriously in error; (2) values for the derived kinetic constants are strongly dependent on the transport model selected for the data analysis which underscores the need for rigorous model analysis; (3) corrected kinetic constants may be obtained by either non-linear regression or by a simpler graphical analysis once the correct transport model has been selected and diffusion barrier resistance determined; (4) only corrected kinetic constants should be used for inter-species comparisons or to study the effect of specific interventions on intestinal glucose transport.
Autoradiographic study of smooth muscle cell proliferation in spontaneously hypertensive rats
Authors: Yang H. , Morton W. , Lee R. M. K. W. , Kajetanowicz A. , Forrest J. B.
Published: August 2015

1. The rate of smooth muscle cell proliferation in age-matched 1-4-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was compared using autoradiography.

2. Labelling index, defined as labelled cells/sum of labelled and unlabelled cells × 1000, was obtained from perfusion-fixed superior mesenteric and large mesenteric arteries.

3. In the large mesenteric arteries, the smooth muscle cell labelling indices were similar between the SHR and WKY at all age groups, except at 1 week of age when the smooth muscle labelling index was higher in the SHR.

4. In the superior mesenteric arteries, labelling indices were similar between the rat strains at all age groups.

5. We conclude that, in the SHR, a rapid proliferation of smooth muscle cells in the large mesenteric arteries occurred during the first week of life. This resulted in a higher number of smooth muscle cell layers in the media of muscular arteries.

6. The increased proliferation may play a role in the subsequent development of hypertension in the SHR.
Effects of smoking on changes in respiratory resistance with increasing age
Authors: Coe C. I. , Watson A. , Joyce H. , Pride N. B.
Published: August 2015

1. The oscillation method for measuring total respiratory resistance (Rrs) is a simple method of assessing airway dimensions which can be applied in epidemiological surveys and potentially might be useful for detecting mild airway disease in smokers. However, it is not known whether abnormalities in Rrs are only present when there are also abnormalities in simple spirometric tests.

2. We have compared values of Rrs and its frequency-dependence (fR) using the oscillation technique applied over the frequency range 6-26 Hz in 42 healthy, non-asthmatic men who were never-smokers (aged 26-61 years) and in 41 male cigarette smokers (aged 32-64 years). The results were compared with those for spirometry and the single-breath N2 test which are the most commonly used techniques in epidemiological surveys for detecting the effects of smoking on the lungs.

3. There was a strong trend for Rrs (especially at lower oscillation frequency) and fR to increase with increasing age in smokers. Increases in Rrs and fR were usually present when forced expiratory volume in 1 s was less than 80% of predicted and the forced expiratory volume in 1 s/vital capacity ratio was less than 65%, but abnormal fR was present in some smokers whose spirometry was within conventional normal limits.

4. Abnormalities in Rrs and fR were weakly associated with abnormality of the single-breath N2 manoeuvre.

5. Abnormal fR is normally attributed to uneven narrowing of intrathoracic airways; however, in smokers it was associated with an increase in Rrs at 6 Hz, so we cannot exclude that some of the observed abnormal fR was due to increased dissipation of the applied pressure in the cheeks and extrathoracic airway rather than to in-homogeneities within the lungs.

6. We conclude that the oscillation technique detects abnormalities indicating airway narrowing in some smokers whose spirometry is within normal limits. Hence the technique could be useful in screening programmes aiming to detect early lung damage. The prognostic significance of the additional information provided by measuring Rrs needs to be further assessed.
Direct and indirect measurement of the hepatic extraction ratio of Indocyanine Green in the rat
Authors: Burns E. , Ball C. E. , Christie J. P. , Broadhead G. D. , Tucker G. T. , Bax N. D. S.
Published: August 2015

1. In order to estimate liver blood flow in the rat, the extraction ratio of Indocyanine Green was determined using a two-compartment model fitted to the plasma concentration time data after a single intravenous bolus dose and compared with values obtained directly by transhepatic sampling, both in the intact rat and in an isolated perfused rat liver preparation.

2. There was no agreement between estimates of the extraction ratio obtained by using the kinetic model and the directly measured values.

3. Elimination curves for Indocyanine Green were simulated to yield varied clearance values. Despite a 250% variation in clearance, extraction ratios derived using the two-compartment model were all greater than 0.9 and varied by less than 6%.

4. Estimates of liver blood flow obtained by deriving a value of the extraction ratio of Indocyanine Green using the two-compartment model are inaccurate.
Prostacyclin attenuates both the pressor and adrenocortical response to angiotensin II in human pregnancy
Authors: Pipkin F. Broughton , Morrison R. , O'Brien P. M. S.
Published: August 2015

1. The effects of angiotensin II (ANG II) infusion without and with simultaneous infusion of prostacyclin (PGI2; 1.4 pmol min−1 kg−1; 5 ng min−1 kg−1) have been studied in 16 women in second-trimester pregnancy. Ten received one infusion of ANG II alone, followed by its infusion together with PGI2; the remainder received two identical infusions of ANG II alone as controls.

2. PGI2 administration was associated with a small fall in diastolic pressure (P < 0.01) and a proportionally greater rise in heart rate (P < 0.001). Small rises in basal plasma renin and ANG II concentrations and a fall in aldosterone concentration were not statistically significant.

3. The diastolic pressor response to ANG II was blunted during PGI2 infusion by comparison with controls (P < 0.025); this diminution in response was greatest in patients who had initially been most sensitive to ANG II (P < 0.02).

4. The evoked increment in plasma aldosterone during ANG II infusion was considerably reduced (P < 0.005) in the presence of PGI2.

5. These data further support the hypothesis of a role for PGI2 in relation to the blunted pressor response to ANG II of normal pregnancy. The apparent inhibitory effects of PGI2 on aldosterone secretion may partly explain the previously described dissociation between the renin-angiotensin system and aldosterone in pregnancy.
Exercise tolerance in the heat on low and normal salt intakes
Authors: Hargreaves M. , Morgan T. O. , Snow R. , Guerin M.
Published: August 2015

1. Salt restriction is recommended in the treatment of hypertension and is included in national dietary guidelines, but its effect on exercise in hot conditions has not been extensively studied.

2. The effects of 2 weeks on two levels of salt intake (50 and 150 mmol/day) on the ability to exercise (60% of maximal oxygen uptake) in a hot environment (35°C) were studied in eight healthy normotensive subjects.

3. All subjects were able to complete the exercise load on the two levels of salt intake. No differences in mean oxygen uptake, heart rate or rectal temperature during exercise were observed between the two salt intakes.

4. Plasma sodium, potassium and osmolality were similar on the two salt intakes both before and during exercise. Plasma renin activity and aldosterone concentration were elevated after 2 weeks on the reduced salt intake and remained so during exercise.

5. The estimated sweat rate during exercise was similar on the two salt intakes but the loss of sodium was less on the low salt intake.

6. On the basis of these results it is concluded that moderate salt restriction does not impair the ability to exercise in a hot environment.
A direct method for the diagnosis of human hepatic type 1b and type 1c glycogen-storage disease
Authors: Waddell Ian D. , Hume Robert , Burchell Ann
Published: August 2015

1. Type 1b and type 1c glycogen-storage disease are caused respectively by deficiencies of the glucose-6-phosphate translocase and the phosphate/pyrophosphate translocase of the human hepatic microsomal glucose-6-phosphatase system.

2. Current methods of unequivocally diagnosing type 1b and type 1c glycogen storage disease are indirect and complex.

3. We have therefore developed a simple, rapid and direct microfiltration assay for the glucose-6-phosphate translocase and the phosphate/pyrophosphate translocase.

4. We have demonstrated that the microfiltration assay can be used to directly diagnose type 1b and type 1c glycogen-storage disease in microsomes isolated from hepatic needle-biopsy samples.
Is polyamine synthesis involved in the proliferative response of the intestinal epithelium to urogastrone-epidermal growth factor?
Authors: Goodlad R. A. , Gregory H. , Wright N. A.
Published: August 2015

1. Intestinal epithelial cell proliferation was measured in rats maintained on total parenteral nutriton (TPN), in TPN rats given 300 μg of recombinant human epidermal growth factor (urogastrone-epidermal growth factor, URO-EGF) day−1 kg−1, and in further groups given URO-EGF and difluoromethylornithine (DFMO), an inhibitor of the enzyme ornithine decarboxylase (ODC).

2. URO-EGF significantly increased intestinal cell proliferation throughout the gastrointestinal tract. The proliferative response of the colon was particularly pronounced.

3. DFMO reduced the proliferative effect of urogastrone in the stomach and small intestine. DFMO also reduced URO-EGF-stimulated intestinal cell proliferation in the colon, but to a lesser extent.

4. It is concluded that ODC is essential for effecting the proliferative response of the stomach and small intestine to URO-EGF, but this role may be less important in the colon.
Effects of pimobendan, a novel inotropic agent, on intracellular calcium and tension in isolated ferret ventricular muscle
Authors: Lee J. A. , Ruegg J. C. , Allen D. G.
Published: August 2015

1. In this study we have investigated the effects of a novel inotropic agent, pimobendan (UDCG 115-BS), on skinned and intact ventricular muscle from ferrets.

2. Pimobendan (20 or 100 μmol/l) increased tension at a given free [Ca2+] when applied to skinned ventricular muscle, i.e. it increased the Ca2+ sensitivity of the myofibrils.

3. Tension and intracellular free Ca2+ ([Ca2+]i) were measured simultaneously in intact papillary muscles using the aequorin technique. When 25 μmol/l pimobendan was added to the superfusing solution, a slowly developing positive ionotropic effect was produced, which was accompanied by an increase in the size of the systolic rise in [Ca2+]i (Ca2+ transients) with a similar time course.

4. In order to determine whether pimobendan increased the Ca2+ sensitivity of myofibrils in an intact papillary muscle, we compared the increase in Ca2+ transients and tension observed in response to changes in extracellular [Ca2+] with those observed in response to pimobendan. The result of this comparison was that in intact muscle pimobendan caused no apparent increase in myofibrillar Ca2+ sensitivity.

5. Pimobendan caused an abbreviation of the time course of the Ca2+ transients, but the twitch was slightly prolonged.

6. When isoprenaline was added to the superfusing solution, a positive inotropic effect was produced, which was accompanied by a marked increase in the size of the Ca2+ transients. Isoprenaline caused an abbreviation of the time course of both the Ca2+ transients and the twitch. When the Ca2+ sensitivity of the intact myofibrils was determined as described above, isoprenaline caused a desensitization. Pimobendan produced a sensitization when compared with isoprenaline.

7. These results are consistent with the hypothesis that pimobendan produces an inotropic effect in isolated cardiac muscle which is mediated both by an increase in Ca2+ sensitivity and by an increase in adenosine 3′: 5′-cyclic monophosphate due to its phosphodiesterase-inhibiting activity. Such a combination of activities may be particularly advantageous for an inotropic agent.
Influence of age on glomerular binding of angiotensin II in normotensive and spontaneously hypertensive rats
Authors: Messenger E. A. , Stonier C. , Aber G. M.
Published: August 2015

1. Glomerular angiotensin II (ANG II) binding has been studied in normotensive (NTR) and spontaneously hypertensive (SHR) rats at 5, 10, 15 and 20 weeks of age.

2. Binding of 125I-labelled ANG II by glomeruli from NTR and SHR was similar at 5 and 10 weeks of age, with 5 week values of 426.4 (range 384-469) and 400.2 ± 245 fmol/mg of protein; however, at 15 and 20 weeks ANG II binding by SHR glomeruli was significantly greater than by NTR, with 20 week values of 614.7 ± 245 and 308.3 ± 31.8 fmol/mg of protein, respectively (P < 0.01).

3. The ANG II binding affinity constant (Ka) of glomeruli from NTR and SHR was comparable at 5, 10 and 15 weeks of age, with values of 1.5 (range 1.1-1.9) and 1.08 ± 0.35 nmol/l, respectively, at 5 weeks; whereas at 20 weeks the Ka for SHR glomeruli was significantly greater than for NTR, with values of 1.85 ± 0.45 and 0.66 ± 0.22 nmol/l, respectively (P < 0.001).

4. Age-related changes in glomerular binding of ANG II in SHR were not found to be related to changes in either plasma renin activity or systolic blood pressure.
Effect of subnutrition on normalized muscle force and relaxation rate in human subjects using voluntary contractions
Authors: Bruce S. A. , Newton D. , Woledge R. C.
Published: August 2015

1. Muscle weakness and wasting are well-known consequences of subnutrition, but there have been no published comparisons of these variables in a single muscle or muscle group. We report voluntary force measurements of adductor pollicis muscle in 11 sub-nourished patients normalized for their cross-sectional areas. We also report normalized relaxation rates of these contractions and the results are compared with those obtained in 40 healthy normally nourished subjects.

2. Normalized muscle force was no different in the subnourished group. However, relaxation rate was significantly slower than in the control group.
Mechanisms of the antinatriuretic action of physiological doses of angiotensin II in man
Authors: Seidelin Peter H. , McMurray John J. , Struthers Allan D.
Published: August 2015

1. Angiotensin 11 (ANG II; 1 ng min−1 kg−1) or 5% (w/v) d-glucose (placebo) was infused in six normal male volunteers, pretreated with 500 mg of lithium carbonate, who were undergoing maximal water diuresis.

2. This dose of ANG II caused a circulating increment within the physiological range (27 ± 4 to 48 ± 9 pmol/l).

3. Compared with placebo, ANG II caused a significant fall in urinary sodium excretion (113 ± 13 to 82 ± 10 μmol/min). This antinatriuretic effect occurred without a fall in creatinine clearance (107 ± 3 versus 113 ± 3 ml/min).

4. ANG II caused a significant fall in fractional lithium clearance (28 ± 2 to 23 ± 2%). This may indicate a proximal tubular effect of ANG II.

5. ANG II also reduced fractional distal delivery [(sodium clearance plus free water clearance) divided by creatinine clearance], another measure of proximal tubular outflow. A parallel change in these two separate markers of proximal function supports an action of ANG II at this nephron segment.

6. Furthermore, the antinatriuretic effect of ANG II was unlikely to be due to stimulation of aldosterone secretion because (a) the fall in sodium excretion was temporally dissociated from the rise in aldosterone secretion, (b) potassium excretion also tended to fall during ANG II infusion and (c) aldosterone has a distal nephron effect, while, in this study, proximal nephron fractional reabsorption of sodium increased and distal nephron fractional reabsorption of sodium was unchanged.

7. These observations suggest that physiological increments in ANG II can have an antinatriuretic effect in man, which, at least initially, results from increased proximal tubular sodium reabsorption and is independent of the effect of aldosterone.
Urinary Kallikrein Excretion during Potassium Chloride Infusion in Potassium-Adapted Rats: Effect of Amiloride
Authors: Obika L. F. O.
Published: August 2015

1. Urinary kallikrein excretion in the anaesthetized rat was measured during intravenous KCl infusion in control and in K+-adapted rats.

2. The infusion of 0.1 mol/l KCl at 3.0 ml/h for 60 min in control rats resulted in a significant increase in urinary kallikrein excretion, associated with diuresis, natriuresis and kaliuresis.

3. When rats were offered 0.1 mol/l KCl to drink ad libitum for 14 days (K+-adaptation), the basal excretion of kallikrein was higher than in the control rats. In K+-adapted rats, intravenous infusion of 0.1 mol/l KCl resulted in significantly greater increase in urinary kallikrein excretion than in the control rats.

4. The Na+-channel blocker, amiloride (8.5 mg/kg body weight), significantly increased urinary kallikrein excretion immediately after injection in control and K+-adapted rats. However, in the subsequent 60 min, kallikrein excretion decreased markedly to values lower than those before injection of amiloride.

5. When amiloride was superimposed on a continuous 0.1 mol/l KCl infusion in K+-adapted rats, there was an immediate increase in kallikrein excretion. In the subsequent 20 min, kallikrein excretion decreased only to increase again in the next 40 min of KCl infusion.

6. Since amiloride injection reduces urinary kallikrein excretion in control and K+-adapted rats, the results suggest that urinary kallikrein excretion in the rat is through a mechanism(s) affected by amiloride. The high urinary kallikrein excretion and the greater response to KCl infusion in K+-adapted rats suggest that the K+-transport mechanism is more important than the mechanism affected by amiloride.
Effects of Insulin on Glucose Metabolism in Skeletal Muscle from Septic and Endotoxaemic Rats
Authors: Leighton Brendan , Dimitriadis George D. , Parry-Billings Mark , Bond Jane , de Vasconcelos Paulo R. L. , Newsholme Eric A.
Published: August 2015

1. The effects of non-lethal bacteraemia or endotoxaemia on insulin-stimulated glucose metabolism were studied in isolated, incubated soleus muscle of rats after 24 and 48 h.

2. The insulin-stimulated rates of lactate formation and glycogen synthesis were similar in muscles isolated from control and bacteraemic rats.

3. Endotoxaemia increased the rates of lactate formation, at all levels of insulin, both at 24 h (∼ 32%) and 48 h (∼ 26%). Endotoxaemia did not alter the sensitivity of glycolysis to insulin.

4. Endotoxaemia decreased the rates of glycogen synthesis at all concentrations of insulin both at 24 h (∼ 39%) and 48 h (∼ 23%).

5. The increase in the rate of glycolysis was related in a dose-dependent manner to the amount of endotoxin given to the animals.

6. Endotoxaemia decreased plasma tri-iodothyronine levels (41%). However, the effects of endotoxaemia (48 h) on glucose metabolism in muscle are similar to those caused by hyperthyroidism. In hypothyroid rats, endotoxin administration increased the rates of glycolysis in muscle in vitro.

7. It is concluded that there are enhanced basal and insulin-stimulated rates of glycolysis in soleus muscle from endotoxaemic rats. This may be due to both increased glucose transport and decreased glycogen synthesis.
Role of Thromboxane A2 as a Mediator of Platelet-Activating-Factor-Induced Aggregation of Human Platelets
Authors: McCulloch R. K. , Summers J. , Vandongen R. , Rouse I. L.
Published: August 2015

1. At present it is unclear whether platelet-activating-factor (PAF)-induced aggregation is mediated by thromboxane. To obtain further information about this event we have compared the affects of aspirin on platelet aggregation and secretion induced by PAF and collagen.

2. Collagen and PAF induced aggregation and secretion in human platelets in a dose-related manner.

3. Aspirin inhibited the magnitude of both platelet aggregation and secretion induced by PAF and collagen, but the degree of inhibition was much greater for collagen.

4. Aspirin strongly inhibited the aggregation rate of collagen-induced platelet aggregation, but had no measurable effect on the rate of PAF-induced aggregation.

5. Inconsistencies reported in previous studies of the effect of aspirin on PAF-induced platelet aggregation may be explained, in part, by the doses of PAF used and the method of inactivating cyclo-oxygenase (in vitro compared with in vivo).

6. Our results suggest that the initial events of PAF-induced aggregation are independent of thromboxane A2 formation and that thromboxane A2 plays only a minor role in the later phase of PAF-induced aggregation.
Time Course of Development of Changes in the Structure and Reactivity of Small Veins from Portal Hypertensive Rabbits
Authors: Juhl Claus Orloff , Jensen Lone Susanne , Mulvany Michael John
Published: August 2015

1. Myographic and histological techniques were used to study the mechanical and morphological properties of oesophageal and mesenteric veins from rabbits subjected to 0, 4, 14 and 90 days of partial portal vein stenosis.

2. The stenosis caused an immediate increase in portal pressure from 10.5 mmHg (1.4 kPa) to 20.5 mmHg (2.7 kPa); the pressure returned to the control level by 90 days.

3. The lumen diameter of oesophageal veins was increased by 76% after 4 days and by 147% after 90 days, while that of the mesenteric veins was unchanged. The media thickness in both veins increased rapidly, reaching a maximum at 14 days (82%, oesophageal; 56%, mesenteric) and thereafter decreasing.

4. The contractility of oesophageal veins was transiently decreased (at 4 days), while that of the mesenteric veins was transiently increased (at 14 days).

5. In further experiments, sclerosing of the oesophagus, which is believed to restrict flow without reducing pressure, restricted the increase in lumen diameter of oesophageal veins caudal to the sclerosing site, but did not affect the media thickness.

6. The results suggest that, in oesophageal and mesenteric veins, portal pressure is a primary determinant of media thickness but not of lumen diameter.
Changes in the Haemodynamic Responses to Exercise, Posture and Nitrates after Treatment of Congestive Heart Failure with an Arteriolar Vasodilator
Authors: Thomas Phillip , Dixon Mark S. , Culling William , Sheridan Desmond J.
Published: August 2015

1. Haemodynamic responses to exercise, posture and nitrates were measured before and after 8 weeks of therapy with an arteriolar smooth muscle specific calcium antagonist, nicardipine, in eight patients with congestive heart failure (New York Heart Association class II or III).

2. The acute haemodynamic effects of intravenous nicardipine before and after 8 weeks of oral therapy confirmed its vasodilating properties, with similar end-points to the initial response after the 8 week period.

3. After 8 weeks of oral therapy all patients improved by one New York Heart Association class and treadmill exercise duration was significantly increased. In contrast, sitting bicycle exercise duration was not prolonged, although, at the same peak workload, changes in cardiac output, stroke volume and systemic vascular resistance were significantly improved after 8 weeks of therapy.

4. Sublingual glyceryl trinitrate predominantly affected pulmonary vascular resistance before and after chronic therapy with nicardipine, although the effects were less marked after 8 weeks. In contrast, the systemic vascular effects of glyceryl trinitrate were significantly increased after 8 weeks of therapy with nicardipine.

5. Increased vasodilator responses to sublingual glyceryl trinitrate and exercise after chronic treatment with nicardipine, in the absence of significant residual vasodilatation at rest, suggests that indirect changes in systemic arterioles may accompany and possibly contribute to the clinical improvement in heart failure.
Prolonged Decrease in Blood Pressure after Atrial Natriuretic Peptide Infusion in Essential Hypertension: A New Anti-Pressor Mechanism?
Authors: Singer D. R. J. , Markandu N. D. , Buckley M. G. , Miller M. A. , Sugden A. L. , Sagnella G. A. , MacGregor G. A.
Published: August 2015

1. To study the anti-hypertensive effects of atrial natriuretic peptide (ANP), eight patients with mild to moderate essential hypertension, on no treatment, were infused with α-human ANP (102–126) (37 pmol min−1 kg−1) or placebo for 60 min and observed for a further 4 h on the fifth day of low and high sodium diets in a randomized, cross-over study.

2. Plasma ANP levels increased over 30-fold into the high pathophysiological range during ANP infusion, but had returned to control values by 60 min after the end of infusion. With ANP infusion, there was a large decrease in supine blood pressure which was similar on both the low and high sodium intakes and was maximal 20–40 min after completion of the infusion. These reductions in blood pressure were sustained for a further 4 h after the end of ANP infusion and for 3 h after plasma ANP levels had returned to control values.

3. Maximal urinary sodium excretion increased 10-fold on the low sodium diet (negative sodium balance 20 mmol) and threefold on the high sodium diet (negative sodium balance 30 mmol) during ANP infusion; however, during the 4 h after infusion, urinary sodium excretion was below placebo values. During ANP infusion, packed cell volume increased significantly on both diets but returned to control values by 4 h after the end of infusion.

4. There were no significant changes in plasma renin activity compared with placebo during or after ANP infusion. However, plasma aldosterone was significantly greater than placebo values after the end of ANP infusion on both low and high sodium diets.

5. The sustained fall in blood pressure after ANP infusion appears to be unexplained by changes in sodium balance, packed cell volume and plasma ANP levels. These findings suggest that ANP may have a prolonged action on a pressor mechanism which remains to be defined.
Dependency of Microdissected Nephron Segments upon Oxidative Phosphorylation and Exogenous Substrates: A Relationship between Tubular Anatomical Location in the Kidney and Metabolic Activity
Authors: Torikai Shozo
Published: August 2015

1. In order to examine the possibility of heterogeneity in the dependence of renal tubular cells upon oxidative phosphorylation and exogenous substrates, the effects of antimycin A and substrate deprivation on adenosine 5′-triphosphate (ATP) content were examined in isolated rat nephron segments in vitro at 37°C.

2. Antimycin A (5 μmol/l) caused varying decrements in cell ATP level within 5 min in the following order: proximal tubules > cortical thick ascending limb of Henle's loop (cTAL) > cortical collecting duct (cCD) in the cortex, and thin descending limb of Henle's loop (TDL) > medullary thick ascending limb of Henle's loop (mTAL) > outer medullary collecting duct (omCD) in the inner stripe of the outer medulla. In the thick ascending limb and the collecting duct, the segments located in the cortex were more sensitive than those in the medulla.

3. Substrate deprivation for 30 min markedly decreased the cell ATP content in cortical and medullary proximal tubules and also in medullary TDL, whereas it caused only a slight decrease in cTAL and mTAL with no change in cCD and omCD.

4. Media made hypertonic by the addition of 200 mmol/l NaCl under aerobic conditions, increased the requirement for exogenous substrates in TDL and mTAL, but not in omCD. This stimulation was seen to a lesser extent in media made hypertonic by the addition of mannitol instead of NaCl.

5. Taking into consideration a knowledge of rat kidney architecture and intrarenal gradient of oxygen partial pressure, it is likely that the observed dependency upon both oxygen and exogenous substrates in the renal tubular cells reflects adaptation of such cells to their anatomical location, and to the availability of those substances in situ. Furthermore, extracellular sodium concentration and osmolarity stimulate metabolic requirements to a different extent among the nephron segments.
Mast Cell Heterogeneity in Human Lung Tissue
Authors: Van Overveld F. J. , Houben L. A. M. J. , du Moulin F. E. M. Schmitz , Bruijnzeel P. L. B. , Raaijmakers J. A. M. , Terpstra G. K.
Published: August 2015

1. In this study mast cells were found to comprise 2.1% of total cells recovered by enzymatic digestion of human lung tissue.

2. This mast cell population consisted of 79% formalin-sensitive, Alcian Blue-positive mast cells and 21% formalin-insensitive, Alcian Blue-positive mast cells.

3. By the use of centrifugal elutriation and subsequent Percoll gradient centrifugation, separate mixed cell populations could be obtained in which the mast cell constituents were either of the formalin-sensitive or -insensitive type.

4. Cell suspensions in which formalin-sensitive cells comprised 97% of mast cells contained approximately 1.34 pg of histamine per mast cell, whereas in preparations in which mast cells were 84% formalin-resistant the histamine content was approximately 4.17 pg of histamine per mast cell.

5. The histamine release upon anti-immunoglobulin E challenge of formalin-sensitive mast cells was greater than the release by formalin-insensitive mast cells.

6. After challenge with opsonized zymosan, only formalin-sensitive mast cells were able to release histamine.

7. Leukotriene C4 release was observed when formalin-sensitive mast cells were challenged with antiimmunoglobulin E. Formalin-insensitive mast cells showed no release of leukotriene C4.

8. Prostaglandin D2 release was observed when formalin-insensitive mast cells were challenged with antiimmunoglobulin E. Formalin-sensitive mast cells showed no release of prostaglandin D2.
Metabolic Changes in Human Liver Associated with Pre-Operative Intravenous Nutrition
Authors: Zeiderman M. R. , King R. F. G. J. , Young G. A. , McMahon M. J.
Published: August 2015

1. This study examined the influence of pre-operative intravenous nutrition upon carbohydrate stores, glucose metabolism and protein synthesis in the liver of patients undergoing laparotomy.

2. Thirty patients with gastrointestinal cancer and weight loss (>5 kg in 3 months) were randomized to receive a hospital diet only or a hospital diet plus intravenous nutrition (0.18 g of N + 125 kJ day−1 kg−1) for 3 or 7 days before laparotomy. Patients who had not lost weight received the hospital diet only and formed a control group.

3. Wedge biopsies of liver were obtained at laparotomy and analysed for glycogen concentration, the activity of three key enzymes of glucose metabolism, 6-phosphofructokinase (EC 2.7.1.11), fructose bisphosphatase (EC 3.1.3.11) and hexokinase (EC 2.7.1.1), and the capacity for protein synthesis.

4. Compared with controls and the hospital diet group, both phosphofructokinase and fructose bisphosphatase activity were reduced in patients who received intravenous nutrition, suggesting the utilization of glucose for glycogen synthesis with a reduction in the glycolytic flux. Consistent with these changes, patients who received intravenous nutrition had a significantly higher glycogen concentration compared with the control and hospital diet groups.

5. Maximal rates of protein synthesis were achieved after only 3 days of intravenous nutrition.

6. The provision of intravenous nutrition was associated with changes in hepatic metabolism suggestive of repletion of energy stores and a higher capacity for protein synthesis.
Rapid Correction of Hyponatraemia with Urea may Protect against Brain Damage in Rats
Authors: Van Reeth O. , Decaux G.
Published: August 2015

1. Rapid correction of hyponatraemia in humans has been reported to be associated with central pontine myelinolysis (CPM). In patients with hyponatraemia related to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) we have rapidly corrected hyponatraemia by using urea, without observing clinical CPM. This led us to analyse the brain damage induced by hypertonic saline and by urea when used for the correction of hyponatraemia in a rat model of SIADH.

2. Severe hyponatraemia (serum Na+ < 115 mmol/l) was produced in 28 rats. Seven rats were excluded from statistical analysis because they died during the correction of hyponatraemia, or because they were under- or over-corrected. Normalization of serum Na+ (135–146 mmol/l) was obtained in 48 h by hypertonic saline (group I, n = 7) or urea (group II, n = 8).

3. Despite similar correction of serum Na+ at 24 h and 48 h, all the rats treated with hypertonic saline presented severe brain damage, whereas those treated with urea were free of any brain damage. A third group of rats (n = 6) who spontaneously corrected their serum sodium level and presented mild hyponatraemia at 48 h (129 ± 5.2 mmol/l) were also free of any brain damage.
Comparison between Endogenous Digoxin-Like Immunoreactivity and 86Rb Uptake by Erythrocytes in Extracts of Human Plasma
Authors: Balzan S. , Montali U. , Genovesi-Ebert A. , Biver P. , Fantoni M. , Ghione S.
Published: August 2015

1. To investigate endogenous cardiac glycoside-like compounds in plasma and their ability to inhibit the sodium pump, digoxin-like immunoreactivity [digoxin-like immunoreactive substance(s), DL1S] and 86Rb uptake by erythrocytes were measured in plasma extracts from normal adults, hypertensive adults and neonates.

2. DLIS levels in neonate plasma extracts were significantly higher than those found for normotensive or hypertensive adults. No difference was observed between normotensive and hypertensive subjects. DLIS was significantly increased when boiled plasma was extracted.

3. Extracts of boiled neonate and adult plasma inhibited 86Rb uptake. Instead, when boiling was omitted, no detectable inhibition was found in extracts of plasma from normotensive or hypertensive adult subjects. When present, the inhibition resulted from a depression of the ouabain-sensitive (sodium-pump-mediated) component, and, for the boiled neonate plasma only, also of the ouabain-resistant component. When the data from the different groups were pooled, a statistically significant inverse relationship between DLIS and erythrocyte 86Rb uptake was observed. Furthermore, in a subgroup of samples in which determinations were made before and after boiling in the same samples, an inverse correlation was found between changes in DLIS and changes in ouabain-sensitive (but not ouabain-resistant) 86Rb uptake.

4. Plasma extracts incubated with albumin at a physiological concentration significantly decreased (by approximately 20%) the inhibition of 86Rb uptake observed.

5. These findings support the existence of one or more endogenous compounds which both bind to antidigoxin antibodies and inhibit transmembrane cation transport. Part of this inhibition may, however, not involve the sodium pump. Furthermore, this chemically unidentified substance(s) may be bound to plasma proteins which partly reduce its action in vivo.
Alterations in Cerebrospinal Fluid Angiotensin II by Sodium Intake in Patients with Essential Hypertension
Authors: Kawamura Minoru , Kawano Yuhei , Yoshida Kaoru , Imanishi Masahito , Akabane Satoshi , Matsushima Yohkazu , Kuramochi Morio , Shimamoto Kazuaki , Ito Keiichi , Omae Teruo
Published: August 2015

1. Angiotensin (ANG) levels were measured in the cerebrospinal fluid of 15 patients with essential hypertension on a high sodium diet for 1 week and on a low sodium diet for a further week. ANGs were determined using a system of extraction by Sep-Pak cartridges followed by h.p.l.c. combined with radioimmunoassay.

2. Sodium depletion resulted in increases of ANG II in the cerebrospinal fluid from 1.16 ± 0.38 (sem) to 1.83 ± 0.43 fmol/ml (P < 0.01) and of ANG III from 0.65 ± 0.11 to 0.86 ± 0.15 fmol/ml (P < 0.01).

3. The ANG II level in the cerebrospinal fluid was found to be unchanged and recovery of added ANG II was approximately 90%, even after incubation for 3 h, on both diets. Thus, it is unlikely that ANG II is produced or degraded in the cerebrospinal fluid in vitro.

4. There was no significant correlation between the cerebrospinal fluid and the plasma ANG II concentration on the low sodium diet.

5. These results suggest that the cerebrospinal fluid ANG II level increases with sodium depletion, and that the effect of the level of ANG II on the activity of the angiotensin-forming system in the central nervous system may be assessed by determination of ANG II in the cerebrospinal fluid in patients with essential hypertension.
Intracellular pH Clamping of Human Leucocytes: A Technique for Determination of Cellular Buffering Power and Na+/H+ Antiport Characteristics
Authors: Ng L. L. , Dudley C.
Published: August 2015

1. A modified method is described for holding the intracellular pH of leucocytes at different values for prolonged periods of time.

2. Using ammonium sulphate at a final concentration of 8 mmol/l, the buffering power of leucocytes was measured at different internal pH values.

3. A marked dependence of buffering power on internal pH was found. As internal pH was lowered below 7.0, buffering power rose steeply. Above this value, buffering power remained approximately constant. This property may be one factor preventing intracellular acidosis under stress.

4. This method is also suitable for the study of Na+/H+ antiport activity. The addition of external Na+ to cells acid-loaded to an internal pH of 6.7 led to an ethyl isopropyl amiloride-sensitive 1:1 stoichiometric exchange of external Na+ for internal H+.
Effect of Aluminium on Superoxide Dismutase
Authors: Shainkin-Kestenbaum Ruth , Adler Andrew J. , Berlyne Geoffrey M. , Caruso C.
Published: August 2015

1. The effect of Al3+ on superoxide dismutase in vitro was studied, since in uraemia there is excessive superoxide production and frequently an elevated serum Al3+ level. Thus, the protective role of superoxide dismutase is particularly important.

2. Al3+ in concentrations similar to those found in the serum of uraemic patients inhibits superoxide dismutase activity. The degree of inhibition is directly proportional to the Al3+ level.

3. The combination of excessive oxygen free radical production with an increased Al3+ level may contribute to a variety of complications, including aluminium dementia or initiation and promotion of carcinogenic processes, which are known to be more common in uraemic patients.
Endogenous Digoxin-Like Immunoreactive Factor and Digitalislike Factor Associated with the Hypertension of Patients Receiving Multiple Alkylating Agents as Part of Autologous Bone Marrow Transplantation
Authors: Graves Steven W. , Eder J. Paul , Schryber Susan M. , Sharma Kiran , Brena Anne , Antman Karen H. , Peters William P.
Published: August 2015

1. Hypertension is a complication of autologous bone marrow transplantation when therapy includes multiple alkylating agents. We have sought to identify the factors underlying this hypertension. We measured weight, serum creatinine, plasma renin activity, aldosterone and digoxin-like immunoreactive factor (DL1F), by digoxin radioimmunoassay, in 18 patients. Plasma catecholamines were also measured in five patients.

2. Of the 18 patients studied, 15 became hypertensive. The variable most consistently associated with these individuals' hypertension was DLIF activity which was increased in 14 of the 15 hypertensive patients (P = 0.055, Fisher exact test). Serum creatinine was increased at some point in seven of the 15 hypertensive patients, weight was increased in five and plasma renin activity and aldosterone were increased in one. Catecholamines were not increased in any of the five patients in which they were measured.

3. The association between changes in mean arterial pressure (MAP) and changes in DL1F for the group as a whole was assessed by analysing one data pair per patient, representing the maximal MAP. This correlation was significant (r = 0.75, P = 0.001).

4. Within individual patients, changes in MAP and changes in serum DLIF concentrations were significantly correlated (r > 0.50, P < 0.05) in six of 15 hypertensive patients.

5. Digitalis-like factor (DLF) was measured by inhibition of (Na+,K+)-adenosine 5′-triphosphatase in five patients and DLF and DLIF were significantly correlated (r = 0.81, P = 0.0001). DLF and MAP were also significantly correlated (r = 0.59, P = 0.002).

6. This represents the first longitudinal study of the relationship between DLIF and blood pressure in hypertensive individuals, and the results suggest that DLIF may contribute to the increased blood pressure in some of these subjects.
Atrial Natriuretic Peptide, Altitude and Acute Mountain Sickness
Authors: Milledge J. S. , Beeley J. M. , McArthur S. , Morice A. H.
Published: August 2015

1. To investigate the mechanisms of acute mountain sickness, 22 subjects travelled to 3100 m by road and the following day walked to 4300 m on Mount Kenya. Control measurements were made over 2 days at 1300 m before ascent and for 2 days after arrival at 4300 m. These included body weight, 24 h urine volume, 24 h sodium and potassium excretion, blood haemoglobin, packed cell volume, and symptom score for acute mountain sickness. In 15 subjects blood samples were taken for assay of plasma aldosterone and atrial natriuretic peptide.

2. Altitude and the exercise in ascent resulted in a marked decrease in 24 h urine volume and sodium excretion. Aldosterone levels were elevated on the first day and atrial natriuretic peptide levels were higher on both altitude days compared with control.

3. Acute mountain sickness symptom scores showed a significant negative correlation with 24 h urinary sodium excretion on the first altitude day. Aldosterone levels tended to be lowest in subjects with low symptom scores and higher sodium excretion. No correlation was found between changes in haemoglobin concentration, packed cell volume, 24 h urine volume or body weight and acute mountain sickness symptom score.

4. Atrial natriuretic peptide levels at low altitude showed a significant inverse correlation with acute mountain sickness symptom scores on ascent.
Genetic Factors in the Development of Nephropathy in Diabetic Lewis and Da Rats
Authors: Payton Colin D. , Boulton-Jones J. M.
Published: August 2015

1. Streptozotocin was used to induce diabetes in two inbred strains of rats, Lewis and DA, known to have different glomerular properties.

2. Dietary protein intake, weight and plasma glucose were monitored during the course of the experiment, and, at regular intervals, urine collections were made utilizing metabolic cages.

3. No significant differences were found in protein intake or plasma glucose between the two strains.

4. Proteinuria was higher in the diabetic Lewis rats than in the diabetic DA rats, and the difference became progressively greater with the passage of time. After 6 months of diabetes, the median values for proteinuria were 19.9 mg/24 h in the Lewis rats and 9.0 mg/24 h in the DA rats.

5. Electron microscopic examination revealed a greater degree of mesangial expansion in the glomeruli of the Lewis rats than in those of the DA rats after 6 months of diabetes. The median fractional mesangial area was 44.8% in the diabetic Lewis rats and 31.4% in the diabetic DA rats.

6. These results suggest that Lewis rats possess an inherited susceptibility to diabetic nephropathy, and that DA rats are relatively resistant. These differences in susceptibilities support the hypothesis that inherited glomerular properties determine an individual's susceptibility to diabetic nephropathy.