bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Antidiuretic Effect of Chronic Hydrochlorothiazide Treatment in Rats with Diabetes Insipidus: Renal Mechanisms
Authors: Shirley D. G. , Walter S. J. , Laycock J. F. 
Published: August 2015

1. Brattleboro rats with hereditary diabetes insipidus were maintained in metabolism cages for 12–14 days. During the final 5–7 days hydrochlorothiazide was added to the food of half the animals, resulting in a sustained antidiuresis. At the end of this time all rats were anaesthetized and their renal function was investigated.
2. Water, sodium and potassium excretion rates during anaesthesia were similar to their respective values during the final period in metabolism cages.
3. Total glomerular filtration rate and superficial nephron filtration rate were similar in untreated and thiazide-treated animals. Fractional fluid reabsorption in proximal convoluted tubules, as measured by tubular fluid/plasma inulin concentration ratios in late surface convolutions, was moderately increased in the thiazide-treated rats, and was associated with a small reduction in the volume of fluid delivered to more distal nephron segments.
4. The osmolality of renal papillary interstitial fluid from thiazide-treated rats was considerably greater than that from untreated animals. There was also a small increase in papillary fluid sodium concentration.
5. It is concluded that the mechanism of the sustained antidiuresis during chronic hydrochlorothiazide administration in diabetes insipidus differs from that of the acute response. The changes in proximal tubular function during chronic thiazide treatment only partially account for the reduction in urine volume; it seems probable that the raised papillary osmolality, by enhancing water reabsorption at sites beyond the proximal tubule, makes a greater contribution to the antidiuresis.
Beneficial Effect of Low Phosphorus Diet in Uraemic Rats: A Reappraisal
Authors: Laouari Denise , Kleinknecht Claire , Cournot-Witmer Giulia , Habib Renée , Mounier Françoise , Broyer Michel 
Published: August 2015

1. Diets deficient in phosphorus have been shown to preserve the renal function of uraemic rats, but the role of concomitant alterations in the intake of other nutrients caused by such diets was not elucidated.
2. Five groups of uraemic rats were compared. Three (A, B, C) received (ad libitum) diets deficient (0·03%), low (0·2%) or normal (0·5%) in P. Two groups (D, E) received restricted amounts of 0·2% and 0·5% P diets by pair-feeding with group A rats.
3. Phosphorus deficient diet resulted in marked anorexia, growth arrest, low P and high calcium plasma levels and severe rickets, but renal function became stabilized. Groups B and C had both higher total food intake and weight gain but a significantly higher mortality rate. After 36 weeks, mortality was 90% in these groups, and was 19%, 28% and 44% in groups A, D and E rats respectively, despite a higher P consumption in group E than in group B rats.
4. Normal P diet was associated with severe renal calcium deposits and high calcium heart content, which were related to the degree of hyperparathyroidism evaluated by bone histology.
5. Preservation of renal function was mainly mediated by reduction in some other components of the diet and not by P restriction itself. Normal P diet with restricted dietary allotments had little adverse effect on survival, and its influence on renal histology is not easy to explain.
6. Restriction in P sufficient to cause moderate hypophosphataemia, disappearance of phosphaturia and to prevent hyperparathyroidism without causing anorexia and other severe side effects, had little or no beneficial effect on renal deterioration.
The Responses to Water Deprivation in Lithium-Treated Patients with and without Polyuria
Authors: Morgan D. B. , Penney M. D. , Hullin R. P. , Thomas T. H. , Srinivasan D. P. 
Published: August 2015

1. Urine osmolality and plasma and urine arginine vasopressin (AVP) were measured before, during and at the end of 23 h of water deprivation in four groups of subjects. There were eight non-polyuric manic-depressive patients taking lithium (the lithium group), seven manic-depressive patients taking other psychotropic drugs but not lithium (the other drug group), seven healthy subjects (the control group) and three lithium-treated patients with polyuria (the polyuric lithium group).
2. The lithium group had a resistance to the effect of AVP on the renal tubule with a fivefold increase in AVP excretion at a given urine osmolality. However, their water homoeostasis was intact as they lost no more weight during water deprivation than did the control group.
3. The relationship beween urine osmolality and AVP excretion has been defined from these results and the effect of lithium treatment on it has been characterized. The results suggest that lithium competitively inhibits the effect of AVP on the renal concentrating mechanism but does not decrease the ‘theoretical’ maximum urine osmolality.
4. The other drug group had a high basal urine flow which was due to a primary increase in water intake. The responsiveness of the renal concentrating mechanism to AVP was the same in this group as in the control group.
5. The polyuric lithium group had the highest basal urine flow and lost the greatest amount of weight during water deprivation. Neither urine osmolality nor AVP excretion was at a maximum in the basal state, as both increased during water deprivation. These relationships between urine osmolality and AVP excretion indicated a much greater resistance to AVP than in the other lithium-treated patients.
6. We suggest that these patients are polyuric as they become thirsty and drink before their AVP secretion increases to levels high enough to overcome the resistance to AVP. The results suggest, however, that in the basal state their water intake may be more than the minimum determined by the resistance to AVP.
Characterization of Renal Prostaglandin E Responsiveness in Decompensated Cirrhosis: Implications for Renal Sodium Handling
Authors: Epstein Murray , Lifschitz Meyer , Ramachandran M. , Rappaport Kenneth 
Published: August 2015

1. It has been suggested that endogenous renal prostaglandin E (PGE) constitutes a determinant of renal haemodynamics and renal sodium handling in patients with cirrhosis. We have accordingly assessed the effects of augmenting endogenous prostaglandins on renal function. We utilized water immersion to the neck since previous studies demonstrated that the redistribution of blood volume and concomitant central hypervolaemia thus induced produces a prompt and marked augmentation of PGE excretion in normal man.
2. Thirteen cirrhotic patients were studied twice while in balance on a daily 10 mmol of sodium/100 mmol of potassium diet during control and during water immersion. Urinary PGE was determined hourly for 6 h.
3. Cirrhotic patients manifested a wide continuum of responses characterized by either a sluggish or barely discernible natriuretic response (n = 5) or an appropriate natriuretic response (n = 8).
4. Water immersion to the neck resulted in a highly significant increase in mean UPGEV, which was threefold that manifested by normal subjects studied under identical conditions. Furthermore, cumulative sodium excretion during immersion correlated with PGE excretion (P &lt; 0·05).
5. These findings, together with the results of studies utilizing prostaglandin synthase inhibitors, are consistent with the postulate that renal PGE may play a role in the alterations of renal function in decompensated cirrhosis.
Role of Enhanced Sympathetic Nervous System Activity and Reduced Na+,K+-Dependent Adenosine Triphosphatase Activity in Maintenance of Elevated Blood Pressure in Obesity: Effects of Weight Loss
Authors: Sowers J. R. , Whitfield L. A. , Beck F. W. J. , Catania R. A. , Tuck M. L. , Dornfeld L. , Maxwell M. 
Published: August 2015

1. To investigate factors regulating blood pressure in obesity we have compared Na+ transport mechanisms and plasma noradrenaline (NA) responses to upright posture and isometric hand grip exercise in obese patients with transport mechanisms and NA responses in age, sex and race matched non-obese subjects. In the obese subjects we examined the effects of caloric restriction and weight reduction over a 12 week period on intracellular erythrocyte cation concentrations, Na+,K+-dependent ATPase activity and 86Rb uptake as well as responses of NA, plasma renin activity (PRA), aldosterone and mean arterial pressure to posture and isometric exercise.
2. Obese patients had greater (P &lt; 0.05) basal supine plasma NA as well as enhanced NA responses to upright posture and exercise. Supine plasma NA as well as NA responses were reduced (P &lt; 0.05) after 4 weeks caloric restriction and PRA and aldosterone responses were decreased (P &lt; 0.05) after 8 weeks caloric restriction. Plasma NA at the onset of the diet correlated (r = 0.68, P &lt; 0.01) with blood pressure, and decrements in NA and blood pressure were also related (r = 0.60, P &lt; 0.01). Reductions in supine PRA and supine plasma NA during wieght loss were correlated (r = 0.55, P &lt; 0.05) and the reduction in PRA may therefore be secondary to a decrease in sympathetic nervous system activity.
3. The intracellular Na+/K+ ratio in erythrocytes was greater in the obese patients than in non-obese controls whereas erythrocyte Na+,K+-ATPase activity and 86Rb uptake in obese patients was reduced (P &lt; 0.01). There were significant negative correlations between Na+,K+-ATPase activity and 86Rb uptake and the degree of obesity. Although Na+,K+-ATPase and 86Rb increased and intracellular Na+ decreased during the 12 weeks of weight loss, they remained altered compared with values in non-obese subjects.
Riboflavin Analogues: A Novel Class of Antihypertensive Drugs
Authors: Trachewsky D. , Kem D. C. 
Published: August 2015

1. Riboflavin analogues were tested in three hypertensive rat models: the DOCA-salt hypertensive rat, spontaneously hypertensive rats (SHR) and Dahl S rats.
2. When 1.6 mg of 7,8-dimethyl-10-formyl-methylisoalloxazine (FMI) or 7,8-dimethyl-10-(2′-hydroxyethyl)isoalloxazine (HEI) was administered with 3.0 mg of DOCA twice weekly for 9 weeks, the systolic blood pressure (SBP) of the unanaesthetized rats rose to only 136 ± 5 mmHg compared with 165 ± 5 mmHg during DOCA treatment alone. The analogues blunted the retention of iliopsoas muscle Na+ and water due to DOCA.
3. In subsequent studies, the more potent riboflavin analogue 7,8-dimethyl-10-(3-chlorobenzyl)isoalloxazine (CBI) was employed. Administration of 0.5 mg of CBI/100 g body wt. twice weekly for 7 weeks lowered the SBP of the unanaesthetized SHR from 188 ± 7 mmHg to 148 ± 2 mmHg. The rats tolerated the medication well. CBI was more effective than hydrochlorothiazide, which at 2.2 mg/100 g body wt. daily only lowered the SBP to 167 ± 5 mmHg. The combined administration of CBI and hydrochlorothiazide produced an additive effect in that the SBP was reduced to 126 ± 4 mmHg.
4. CBI treatment resulted in a 36% and 11% decrease in the iliopsoas muscle Na+ concentration and water content respectively, suggesting that the untreated SHR is retaining Na+. The hydrochlorothiazide-treated SHR exhibited elevated levels of serum aldosterone. There was a profound suppressive effect of CBI on the secondary hyperaldosteronism generated by hydrochlorothiazide which was also reflected in the iliopsoas muscle K+ concentration.
5. In contrast to the SHR, the administration to the Dahl S rats of CBI for 8 weeks at 0.5 mg/100 g body wt. twice weekly reduced neither their SBP nor their iliopsoas muscle Na+ and water contents.
6. These results are consistent with our hypothesis that the antihypertensive actions of the riboflavin analogues are closely associated with their ability to modify the effects of mineralocorticoids on Na+ balance. These data suggest that riboflavin analogues also decrease aldosterone production and may function as dual-mechanism diuretic agents with K+ sparing properties and thus act as a novel class of antihypertensive drugs.
Acute Reduction in Inactive Renin after Stimulation of Active Renin by Converting Enzyme Inhibition (CEI) in Man
Authors: Hsueh W. A. , Goldstone R. , Carlson E. J. , Horton R. 
Published: August 2015

1. Administration of a single dose of captopril, 50 mg, to normal man (n = 7) on a low salt intake induced a 12.5 ± 0.9-fold rise in active renin. The rise in active renin was associated with a reciprocal decrease in circulating inactive renin to 10% or less of control levels.
2. Repeated administration of captopril (50 mg p.o. q 6 h × 3 days) to normal man resulted in increases in both active and inactive renin concentration in plasma.
3. When a single dose of captopril was administered to three patients with hyporeninaemic hypoaldosteronism, no changes in their circulating levels of active or inactive renin occurred.
4. These observations suggest that renal conversion of inactive to active renin may be important in active renin production.
Reversible Renal Nerve Denervation in the Cat: Effects on Haemodynamic and Excretory Functions of the Ipsilateral and Contralateral Kidneys
Authors: Golin R. , Stella A. , Zanchetti A. 
Published: August 2015

1. In anaesthetized cats, reversible nenal nerve denervation (cooling of the renal nerves on one side at 4°C for 16 min) was performed and its effects on haemodynamic and excretory functions of the ipsilateral and the contralateral kidneys were studied.
2. Renal nerve cooling did not cause any change in arterial pressure. Slight increase in blood flow, no change in glomerular filtration rate and a large increase in water and sodium excretion occurred in the ipsilateral kidney; simultaneously, no change in blood flow, a slight and transient decrease in glomerular filtration rate, and a significant decrease in diuresis and natriuresis were observed in the contralateral kidney.
3. Ipsilateral and contralateral renal changes were equally evident in the early (minutes 0 to 8) and late phases (minutes 8 to 16) of the cooling period.
4. When renal nerve cooling was repeated after surgical denervation of the contralateral kidney all contralateral effects were abolished.
Interaction of the Sympathetic Nervous System with Vasopressin and Renin in the Maintenance of Blood Pressure in Rats
Authors: Hatzinikolaou Peter , Gavras Irene , North William G. , Brunner Hans R. , Gavras Haralambos 
Published: August 2015

1. Anephric and intact rats were submitted sequentially to catecholamine depletion (‘chemical sympathectomy’) vasopressin inhibition and angiotensin blockade whilst blood pressure and plasma levels of each hormone were monitored.
2. Depletion of catecholamines to 15–25% of baseline levels was associated with significant fall of blood pressure. A close correlation existed between these variables.
3. Chemical sympathectomy caused stimulation of plasma vasopressin, which reached excessively high levels in anephric animals. These were inversely correlated with the levels of depleted catecholamines.
4. Vasopressin inhibition after chemical sympathectomy caused profound and lasting hypotension in anephric rats but only a transient small fall in blood pressure in intact rats. Angiotensin blockade after chemical sympathectomy in intact rats caused a transient small fall in blood pressure; subsequent vasopressin inhibition in these rats caused profound lasting hypotension.
5. It is concluded that resting blood pressure is mainly sustained by the sympathetic nervous system, whereas renin and vasopressin are important back-up mechanisms to maintain compromised blood pressure.
Changes in Blood Pressure, Body Fluids, Circulating Angiotensin II and Aldosterone, with Improved Diabetic Control
Authors: O'hare J. A. , Ferriss J. B. , Twomey B. M. , Gonggrijp H. , O'sullivan D. J. 
Published: August 2015

1. We studied 12 normotensive non-ketotic diabetic patients during poor metabolic control, with sustained hyperglycaemia, and again, after an interval of 3 weeks, when metabolic control was improved. On each occasion we measured blood pressure, total exchangeable sodium, plasma volume, transcapillary escape rate of albumin, and plasma concentrations of angiotensin II and aldosterone.
2. With improved diabetic control there was a small but significant fall in arterial pressure. Total exchangeable sodium was normal when control was poor but rose significantly to above normal with improved control.
3. Plasma volume also rose significantly with improved control, and the transcapillary escape rate of albumin fell and the intravascular mass of albumin rose.
4. Plasma angiotensin II and aldosterone concentrations were significantly above normal during poor metabolic control, but fell to normal with improved control.
5. These findings indicate a resetting of the relationship between blood pressure and exchangeable sodium when diabetic control improves. The association between exchangeable sodium and concentrations of angiotensin II and aldosterone also appears altered in diabetic patients. These changes associated with varying metabolic control must be considered when studying cardiovascular disease in diabetic patients.
Pain and Fatigue after Concentric and Eccentric Muscle Contractions
Authors: Newham D. J. , Mills K. R. , Quigley B. M. , Edwards R. H. T. 
Published: August 2015

1. Normal subjects performed a step test in which the quadriceps of one leg contracted concentrically while the contralateral muscle contracted eccentrically.
2. Maximal voluntary force and the force:frequency relationship were altered bilaterally as a result of the exercise, the changes being greater in the muscle which had contracted eccentrically. Recovery occurred over 24 h.
3. Electromyographic studies using three sites on each muscle showed an increase in electrical activation during the exercise only in the muscle which was contracting eccentrically. Recovery followed a time course similar to that of the contractile properties.
4. Pain and tenderness developed only in the muscle which had contracted eccentrically. Pain was first noted approximately 8 h after exercise and was maximal at approximately 48 h after exercise, at which time force generation and electrical activation had returned to pre-exercise values.
5. Eccentric contractions cause more profound changes in some aspects of muscle function than concentric contractions. These changes cannot be explained in simple metabolic terms, and it is suggested that they are the result of mechanical trauma caused by the high tension generated in relatively few active fibres during eccentric contractions.
Release of a 6-Oxoprostaglandin E1-like Substance from Human Platelets
Authors: Lofts F. J. , Moore P. K. 
Published: August 2015

1. Human platelet-rich plasma incubated at 37°C generates an antiaggregatory prostaglandin which is spasmogenic on gastrointestinal smooth muscle.
2. Platelet-rich plasma from female donors generated more biological activity and was more sensitive to the anti-aggregatory activity of added prostaglandin I2 (PGI2) compared with that from age-matched male controls.
3. After thin-layer chromatography of extracted platelet-rich plasma, biological activity was detected in a zone which co-chromatographed with 6-oxoprostaglandin E1.
4. Neither extracted platelet-rich plasma nor authentic 6-oxoprostaglandin E1 were inactivated following incubation with purified 15-hydroxyprostaglandin dehydrogenase.
5. The relevance of these findings for regulating platelet reactivity is discussed.
The Influence of Different Types of ω3 Polyunsaturated Fatty Acids on Blood Lipids and Platelet Function in Healthy Volunteers
Authors: Sanders T. A. B. , Roshanai Farah 
Published: August 2015

1. Five healthy subjects took a daily supplement of 20 ml of linseed oil for 2 weeks. After a break of at least 6 weeks, the same subjects took a similar amount of MaxEPA (a fish oil fraction) for 2 weeks. The linseed oil supplement provided 9.38 g of linolenic acid (18:3 ω3) and the MaxEPA supplement provided 3.03 g of eicosapentaenoic acid (20:5 ω3) and 2.93 g of docosahexaenoic acid (22:6 ω3). The effects of the supplements on plasma lipid concentrations and on the fatty acid composition of platelet phosphoglycerides were studied.
2. In a second experiment, five male subjects took 5, 10 and 20 g of MaxEPA/day in random order for 3 week periods; each experimental period was separated by a break of at least 6 weeks. These doses of MaxEPA provided 0.83, 1.67 and 3.33 g of 20:5 ω3 and 0.80, 1.61 and 3.22 g 22:6 ω3 respectively. The effects of these supplements on plasma lipid concentrations, the fatty acid composition of platelet phosphoglycerides, template bleeding time and platelet aggregation induced by collagen and the prostaglandin analogue compound U46619 were studied.
3. In the platelet lipids, the proportion of 20:5 ω3 was increased by the 20 ml linseed oil supplement but the increase was small compared with the increase brought about by even 5 g of MaxEPA/day. The proportion of arachidonic acid (20:4 ω3) was substantially decreased by the MaxEPA supplement but not by the linseed oil supplement. The ratio of 20:4 ω6/20:5 ω3 fell from 32:1 in the control periods to 11:1 with 5 g, 7:1 with 10 g and 5:1 with 20 g of MaxEPA/day. The MaxEPA supplement also led to increases in the proportions of 22:5 ω3 and 22:6 ω3 and decreases in those of 20:3 ω6 and 22:4 ω6.
4. Bleeding times tended to be prolonged with the MaxEPA supplement but did not follow any dose-dependent trend. Platelet aggregation induced by both collagen and compound U46619 was not inhibited in vitro.
5. Plasma triglyceride concentrations were lowered by the MaxEPA supplement but not by the linseed oil supplement. Plasma triglyceride concentrations were substantially lowered by 10 g and 20 g of MaxEPA/day. Total plasma cholesterol concentrations were slightly lowered and HDL cholesterol concentrations were slightly increased by 20 g of MaxEPA/day. No other significant differences were noted.