bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium and lithium handling in the isolated hypertensive rat kidney
Authors: Firth J. D. , Raine A. E. G. , Ledingham J. G. G. 
Published: August 2015

1. Isolated kidneys taken from spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY) were perfused over a range of perfusion pressures.
2. Lithium clearance was used as an index of proximal tubule sodium handling.
3. When the perfusate contained an oncotic agent (albumin, 6.7 g/dl) the SHR kidneys performed differently from the WKY kidneys with a reduction in inulin clearance, sodium excretion, fractional sodium excretion and fractional lithium excretion [at 105 mmHg (14 kPa) perfusion pressure, SHR 6.0 ± 1.1% vs WKY 12.6 ± 2.4% (mean ± sem); at 150 mmHg (20 kPa), SHR 17.1 ± 1.6% vs WKY 27.0 ± 2.3%]. Calculated indices of distal tubular function showed no major differences between SHR and WKY.
4. When kidneys were perfused without oncotic agent in the perfusate the differences between SHR and WKY in tubular handling of sodium and lithium were largely abolished.
5. These findings are consistent with the hypothesis that increased sodium reabsorption occurs in the proximal tubules of the kidneys of SHR and suggest that this is an intrinsic property of the kidney, not immediately dependent on neural or humoral factors. Increased sodium reabsorption in the proximal tubule may contribute significantly to the existence of hypertension in the SHR.
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 &lt; 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 &lt; 0.01) and a proportionally greater rise in heart rate (P &lt; 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 &lt; 0.025); this diminution in response was greatest in patients who had initially been most sensitive to ANG II (P &lt; 0.02).
4. The evoked increment in plasma aldosterone during ANG II infusion was considerably reduced (P &lt; 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 &lt; 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 &lt; 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.