bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Sodium-Potassium-Dependent ATPase Inhibition on Noradrenaline-Activated Calcium Sensitivity of Mesenteric Resistance Vessels in Adult Spontaneously Hypertensive Rats
Authors: Mulvany M. J. , Nyborg N. , Nilsson H.
Published: August 2015

1. We have investigated the noradrenaline-activated calcium sensitivity of 150 μm mesenteric resistance blood vessels from spontaneously hypertensive and control Wistar-Kyoto rats.

2. Under control conditions the spontaneously hypertensive rat blood vessels had a greater calcium sensitivity than the Wistar-Kyoto rat vessels.

3. In the presence of 1 mmol of ouabain/l, a treatment known to inhibit the sodium-potassium-dependent ATPase, the responses of the spontaneously hypertensive rat blood vessels were reduced more than those of the Wistar-Kyoto rat blood vessels, so that the responses of spontaneously hypertensive rat and Wistar-Kyoto rat blood vessels were then similar.

4. Similar results were obtained by removing external potassium, a procedure which should also inhibit the sodium-potassium-ATPase.

5. The results suggest that the greater noradrenaline-activated calcium sensitivity of spontaneously hypertensive rat blood vessels may be associated with an increased sodium-potassium-ATPase activity.
Pre- and Post-Junctional Adrenergic Mechanisms and Hypertension
Authors: Vanhoutte P. M. , Webb R. C. , Collis M. G.
Published: August 2015

1. The ability of the blood vessel wall to synthesize noradrenaline is augmented at the early stages of genetic hypertension in animals. It usually is normal, or reduced in chronic hypertension.

2. The exocytotic release of noradrenaline is greater than normal, in the early stages of a number of experimental models of hypertension.

3. Postjunctional receptors for noradrenaline are not uniform throughout the vascular tree. Their sensitivity changes during the development of high blood pressure.

4. In chronic hypertension neuronal uptake and the extraneuronal disposition of released noradrenaline is depressed in the heart, but accelerated in the blood vessel wall.

5. The adrenergic neuro-effector interaction undergoes a diverging long-term adaptation in the heart and the blood vessels of hypertensive animals. In the former this tends to increase, but in the latter to reduce, the efficiency of sympathetic nervous control.
Dissociation between Central and Peripheral Noradrenergic Activity in Essential Hypertension
Authors: Lake C. R. , Polinsky R. J. , Gullner H.-G. , Ebert M. H. , Ziegler M. G. , Bartter F. C. , Kopin I. J.
Published: August 2015

1. Eleven patients with essential hypertension and nine healthy normotensive volunteer subjects, all without a neurological disorder, had blood drawn and cerebrospinal fluid sampled for analysis of noradrenaline (NA).

2. Cerebrospinal fluid NA levels were elevated (P<0.01) in the hypertensive patients but plasma levels of NA were similar between groups.

3. The results suggest there is noradrenergic hyperactivity in the central nervous system which is not reflected in abnormal peripheral sympathetic nervous system function in this group of patients.
A Hierarchical Organization of Blood Pressure during Natural Behaviour in Rat and the Effects of Central Catecholamine Neurons Thereon
Authors: Ledoux J. E. , Tucker L. W. , Del Bo A. , Harshfield G. , Green Lori , Talman W. T. , Reis D. J.
Published: August 2015

1. Changes in arterial pressure associated with a repertoire of natural behaviour patterns in the rat were examined.

2. A hierarchy of such changes was found. Eating and drinking were associated with higher pressures than grooming and exploration, which in turn were associated with higher pressures than resting.

3. Desynchronized sleep was associated with higher pressures than slow-wave sleep.

4. Lesions of the catecholamine neurons of the A2 region of the medulla did not disrupt the normal hierarchy but resulted in an exaggerated pressor response.
Angiotensin Activates Sympathetic Reflexes in the Anaesthetized Cat
Authors: Clough D. P. , Hatton R. , Conway J. , Adigun S. A.
Published: August 2015

1. Lower-body subatmospheric pressure has been used to stimulate sympathetic reflexes in anaesthetized cats and the effects of an angiotensin converting enzyme inhibitor and [Sar1, Ala8]angiotensin II have been investigated on this reflex.

2. At the prevailing level of renin activity (2.9-3.2 ng of angiotensin I h−1 ml−1) the converting enzyme inhibitor had no effect on blood pressure yet it potentiated the initial fall in blood pressure caused by the reduced pressure and it impaired its recovery. After 10 min, therefore, blood pressure was still reduced after converting enzyme inhibitor treatment whereas in control experiments full recovery occurred within 30 s.

3. When converting enzyme inhibitor was given 75 s after the start of a 10 min period of reduced pressure, at a time when plasma renin activity had not been increased, it caused a greater and more sustained fall in pressure than it caused when administered alone. The angiotensin II antagonist, [Sar1,Ala8]angiotensin II, produced similar effects.

4. These findings suggest that the renin-angiotensin system interacts with the sympathetic nervous system to maintain systemic arterial pressure.
Blood Pressure and Heart Rate Responses to Centrally Administered Substance P Are Increased in Spontaneously Hypertensive Rats
Authors: Unger T. , Rockhold R. W. , Yukimura T. , Rettig R. , Ganten D.
Published: August 2015

1. The cardiovascular effects after intracerebroventricular injections of substance P were investigated in normotensive Wistar-Kyoto and in spontaneously hypertensive rats.

2. Substance P increased blood pressure in both rat strains. Wistar-Kyoto rats responded with moderate, dose-dependent blood pressure increases, and heart rate decreased; spontaneously hypertensive rats showed two- to three-fold increased pressor effects and, concomitantly, marked heart rate increases to intracerebroventricular injections of substance P.

3. Sino-aortic baroreceptor denervation rendered Wistar-Kyoto rats supersensitive to intracerebroventricular substance P to a similar degree as unoperated spontaneously hypertensive rats. Sino-aortic denervation had no effect on the blood pressure responses to the peptide in spontaneously hypertensive rats.

4. The central pressor actions of substance P could be markedly attenuated. by intracerebroventricular pretreatment with the derivative of γ-aminobutyric acid, baclofen.

5. We conclude that the baroreceptor reflex is disturbed in spontaneously hypertensive rats. Substance P may contribute to the pathogenesis of hypertension. The effector pathways appear to be different from angiotensin.
Plasma Catecholamines and Plasma Renin Activity at Birth and during the First Days of Life
Authors: Leonetti G. , Bianchini C. , Picotti G. B. , Cesura A. , Caccamo Letizia , Marini A.
Published: August 2015

1. Plasma noradrenaline and adrenaline concentrations and plasma renin activity were measured in 21 mothers at delivery and in their babies at birth (umbilical cord blood) and on days 1 and 5 of extrauterine life.

2. At birth plasma renin activity was significantly higher in the newborn than in mothers. Plasma renin activity increased further, but not significantly, on day 1 of life and significantly decreased on day 5. On day 5, 10 min head-up tilting caused no change in plasma renin activity.

3. Plasma noradrenaline in the newborn was higher than in mothers at birth and significantly decreased thereafter. Plasma adrenaline levels at birth were similar in the newborn and their mothers and significantly lower in the newborn in subsequent days. Tilting caused no increase in either plasma adrenaline or noradrenaline levels.

4. No correlation was found between plasma noradrenaline and adrenaline levels and plasma renin activity, or between noradrenaline, adrenaline or plasma renin activity and blood pressure.
Effects of Tonin on Vascular Smooth Muscle of the Hypertensive Rat and Normal Rabbit
Authors: Garcia R. , Schiffrin E. L. , Thibault G. , Boucher R. , Genest J.
Published: August 2015

1. The response of arterial smooth muscle to noradrenaline was studied in one-clip hypertensive rats with or without the contralateral/kidney and in normotensive rabbits.

2. Strips of aorta from one-kidney, one-clip hypertensive animals were less responsive to noradrenaline than normotensive control rats. The contractile response of strips from two-kidney, one-clip hypertensive animals was not different from the control group. These results suggest that the mechanisms responsible for the lesser reactivity in the one-kidney hypertensive group are not a consequence of elevated blood pressure itself, but may be related to the intrinsic contractility of aortic smooth muscle.

3. Tonin potentiated the contraction induced by noradrenaline in aortic strips from hypertensive and normotensive rats. However, this effect was more important in the one-kidney, one-clip hypertensive animals. In the aortic and mesenteric strips from normal rabbits, tonin produced not only potentiation to noradrenaline but direct contraction.

4. The potentiation to noradrenaline and the direct effect of tonin were not affected by a variety of antagonists but were blocked by a calcium ion antagonist, verapamil, suggesting that tonin may act directly on vascular smooth muscle through mechanisms which might be mediated by calcium ions.
Haemodynamics of Stable Renal Transplant Recipients
Authors: Kim K. E. , Bates O. , Lyons P. , Pitone J. , Martinez E. W. , Valvo E. , Sabanayagam P. , Bower R. , Swartz C. , Onesti G.
Published: August 2015

1. Haemodynamics, blood volume, plasma renin concentration and creatinine clearance were evaluated in 24 stable renal transplant recipients.

2. The mean cardiac index of the transplant recipients was not different from that of the normal subjects.

3. The transplant recipients comprised eight hypertensive and 16 normotensive patients. The mean cardiac index was the same in eight hypertensive and 16 normotensive patients. Thus the hypertension of stable renal transplant recipients is sustained by a high total peripheral resistance.

4. The mean blood volume, plasma renin concentration and creatinine clearance were similar in eight hypertensive and 16 normotensive patients. Therefore the hypertension of stable renal transplant recipients is not related to blood volume expansion, elevated peripheral renin or low creatinine clearance. The cause of the elevated total peripheral resistance in hypertension in stable renal transplant recipients remains to be elucidated.
Haemodynamic Changes Associatedc with Obesity and High Blood Pressure in Crats with Ventromedial Hypothalamic Lesions
Authors: Reisin E. , Suarez D. H. , Frohlich E. D.
Published: August 2015

1. The haemodynamic and plasma volume changes associated with obesity and high blood pressure were studied in nine male rats with electrolytic ventromedial hypothalamic lesions and their paired sham-operated controls. Body weight and arterial pressure were greater in the rats with ventromedial hypothalamic lesions (565 ± 16 vs 462 ± 14 g, P<0.001; 128 ± 3 vs 118 ± 3 mmHg, P<0.05, respectively). Cardiac output was slightly elevated, and that portion of cardiac output distributed to the kidneys was reduced (P<0.001). Plasma volume was contracted in the rats with ventromedial hypothalamic lesions (21.0 ± 0.1 vs 2.8 ± 0.1 ml/100 g, P<0.001).

2. The haemodynamic characteristics of rats in which obesity and mild hypertension have been induced by electrolytic ventromedial hypothalamic lesion are similar to mild obesity essential hypertension in men.
Abnormal Left Ventricular Relaxation in Hypertensive Patients
Authors: Fouad F. M. , Tarazi R. C. , Gallagher J. H. , MacIntyre W. J. , Cook S. A.
Published: August 2015

1. The maximum rates of left ventricular ejection and filling were derived (Fourier analysis) from the left ventricular volume curve (99mtechnetium-human serum albumin gated blood pool studies) in 12 normotensive subjects and 15 hypertensive patients of matched age groups.

2. Average values of cardiac output, ejection fraction, heart rate and left ventricular ejection rate were not significantly different in the two groups.

3. Hypertensive patients had a slower rate of left ventricular filling (P<0.05), suggesting diminished left ventricular compliance in hypertension.
Effect of β-Receptor-Blocking Agents on Cardiovascular Structural Changes in Spontaneous and Noradrenaline-Induced Hypertension in Rats
Authors: Yamori Yukio , Tarazi R. C. , Ooshima Akira
Published: August 2015

1. Continuous intravenous noradrenaline infusion for 1 week into rats by osmotic minipumps significantly increased blood pressure and left ventricular weight.

2. Concomitant α-receptor-blockade infusion significantly lowered blood pressure and the aortic weight without significant reduction in left ventricular weight.

3. Two β-receptor-blocking agents in noradrenaline-infused rats normalized left ventricular weight and significantly reduced the aortic weight, although blood pressure was still higher than control non-infused rats.

4. In 7-week-old spontaneously hypertensive rats, propranolol (perorally for 2 weeks) did not lower blood pressure but reduced significantly cardiovascular protein synthesis ([14C]lysine and [3H]uridine incorporation into non-collagen protein and RNA respectively) in both left ventricle and aorta. This effect was in contrast to hydrallazine, which normalized blood pressure but did not reduce cardiovascular protein synthesis.

5. Results suggest that β-receptors play a modulating role in the structural cardiovascular response to blood pressure.
Renal Blood Flow and Noradrenaline Secretion during Treatment with Propranolol
Authors: De Leeuw P. W. , Punt R. , Birkenhager W. H.
Published: August 2015

1. Fifty-five patients with uncomplicated essential hypertension were admitted to hospital, where 25 of them were treated with propranolol (average daily dose 240 mg) and 30 were left untreated.

2. In all of them renal arteriography was carried out, after which procedure renal plasma flow ([123I]hippuran clearance), cortical blood flow (xenon washout) and renal noradrenaline release were measured.

3. Compared with the untreated hypertensive patients, responders to propranolol (mean blood pressure ≤ 110 mmHg) during treatment showed enhanced cortical blood flow and reduced noradrenaline secretion. Non-responders had reduced cortical flow rates, but increased noradrenaline secretion.

4. Both in the untreated group and in the propranolol-treated group an inverse relationship between arterial noradrenaline concentration and cortical blood flow was found.

5. The results indicate that sympathetic activity may be an important determinant of renal blood flow in hypertension. The effectiveness of propranolol seems to depend upon a reduction in α-adrenergic tone.
Transluminal Balloon Dilatation of Renal Artery Stenosis Causing Hypertension: 18 Months' Experience
Authors: Yune H. Y. , Klatte E. C. , Grim C. E. , Weinberger M. H.
Published: August 2015

1. We have treated 25 patients with renovascular hypertension with balloon catheter dilatation.

2. In 17 patients, surgical treatment was thought to be either risky or difficult due to the presence of a serious medical condition or because of the peripheral location of the lesion.

3. Seventeen patients had atherosclerotic lesions, six patients had fibromuscular dysplasia and one patient had neurofibromatosis and one had stricture of an aorto-renal bypass graft.

4. Of the total group, six in the atherosclerotic group, three patients with fibromuscular dysplasia and the one with neurofibromatosis are normotensive without medications.

5. Five patients with atherosclerosis, two patients with fibromuscular dysplasia and the patient with aorto-renal bypass graft are either normotensive or have reasonable control of blood pressure with medication.

6. Four technical and treatment failures and three major medical complications were encountered. Recurrence of stenosis occurred in eight patients but none of these was in the fibromuscular dysplasia group.
Impaired Lipoprotein Lipase Activation by Uraemic and Post-Transplant Sera
Authors: Crawford G. A. , Mahony J. F. , Stewart J. H.
Published: August 2015

1. Lipoprotein lipase was separated from normal human post-heparin plasma by affinity chromatography and assayed with a 14C-labelled triolein emulsion. No enzyme activity was detected unless whole serum was included in the assay as a source of cofactor, apolipoprotein C-II.

2. After a 10 h fast, serum obtained from 46 normal subjects, eight patients with hypertriglyceridaemia but normal renal function, patients with chronic renal failure (24 undialysed, 20 haemodialysed) and 14 recipients of renal allografts, was added to incubation medium for the assay of lipoprotein lipase to determine the maximum activation of the enzyme.

3. When serum was obtained from normal subjects, maximum activation of the enzyme correlated positively with the concentration of triacylglycerol in the sample. Neither sex nor age had a significant effect on the maximum activation achieved by serum from control subjects.

4. The maximum lipoprotein lipase-activating capacity of serum from uraemic and transplant patients was significantly reduced when compared with serum from healthy controls or from the non-uraemic hypertriglyceridaemic patients.

5. Maximum enzyme activation correlated positively with high-density lipoprotein cholesterol in serum from undialysed patients, but did not correlate positively with total serum triacylglycerols in any of the patient groups. Only in transplant recipients was there a significant inverse relationship between serum creatinine concentrations and maximum enzyme activation.

6. Although lipoprotein lipase activation was impaired in uraemic subjects and renal transplant recipients, this appeared to be due more to the presence of an inhibitor than to cofactor deficiency.
Portal Vein Prostacyclin Activity in Experimental Portal Hypertension in Rats
Authors: Hamilton G. , Rosza I. , Hutton R. , Chow F. P. R. , Dandona P. , Hobbs K. E. F.
Published: August 2015

1. Portal hypertension was produced experimentally in rats by partial ligation of the portal vein.

2. One week later portal veins of these animals were shown to release significantly greater amounts of prostacyclin than control animals.

3. It is postulated that if this response occurs in man, local vasodilatation and inhibition of platelet aggregation may be exacerbatory factors in the severity of haemorrhage from oesophageal varices that complicate portal hypertension.
Identification of N-Monoacetylcystine in Uraemic Plasma
Authors: Gejyo F. , Ito G. , Kinoshita Y.
Published: August 2015

1. An unidentified ninhydrin-positive substance of an acidic nature was detected in the plasma of uraemic patients. This substance was isolated from haemodialysate by ion-exchange chromatography and gel filtration, and identified as a sulphur-containing amino acid: N-monoacetylcystine.

2. The quantitative determination of sulphur amino acids in plasma revealed that the plasma levels of cysteic acid, homocysteic acid, taurine, cystine and cystathionine as well as N-monoacetylcystine in uraemic patients were markedly higher than in normal subjects (P < 0.001 for each). However, the plasma levels of methionine in uraemic patients were within normal limits.
Human Parathyroid Gland Adenylate Cyclase Activity: Inhibition by 24,25-Dihydroxycholecalciferol in vitro
Authors: Cloix J. F. , Ulmann A. , Monet J. D. , Funck-Brentano J. L.
Published: August 2015

1. Plasma membranes were prepared from parathyroid adenomas in patients with primary hyperparathyroidism and from hyperplastic glands obtained from patients with chronic renal insufficiency. The basal and isoproterenol- or sodium fluoride-stimulated adenylate cyclase activities were measured in membranes in the presence of several vitamin D3 metabolites.

2. 24,25-Dihydroxycholecalciferol (10 and 1000 pmol/l) decreased isoproterenol- and sodium fluoride-stimulated adenylate cyclase activities in membranes prepared from parathyroid glands. 1,25-Dihydroxycholecalciferol (1000 pmol/l) inhibited the isoproterenol-stimulated adenylate cyclase activity. 25-Hydroxycholecalciferol and vitamin D3 had no effect on adenylate cyclase activities. Basal adenylate cyclase activity was not affected by any of the vitamin D3 metabolites tested.

3. These results indicate that 24,25-dihydroxycholecalciferol inhibits the isoproterenol- and sodium fluoride-stimulated adenylate cyclase activities in parathyroid tissues. Such an inhibition could explain the very rapid decrease in parathyroid hormone secretion after 24,25-dihydroxycholecalciferol administration that has been previously reported.
The Role of Histamine Receptors in Asthma
Authors: Eiser Noemi M. , Mills Jane , Snashall P. D. , Guz A.
Published: August 2015

1. Eighteen non-asthmatic and 18 asthmatic subjects underwent challenge with increasing doses of histamine from a dosimeter—nebulizer system. Half the subjects in each group were atopic and half non-atopic. Bronchial response was monitored with serial measurements of specific airways conductance (sGaw) and a dose-response curve was constructed for each challenge. In addition, the nine atopic asthmatic patients underwent antigen challenges with a similar technique. In each subject the challenges were repeated, on separate days, after intravenous injections of either sodium chloride solution (150 mmol/l: saline) placebo, chlorpheniramine (an H1-receptor antagonist), cimetidine (an H2-receptor antagonist) or after both antagonists together. Baseline bronchial tone was always comparable within subjects immediately before challenge.

2. Cimetidine had no significant effect on baseline sGaw in any group, whereas chlorpheniramine raised baseline sGaw in the asthmatic subjects. Placebo did not alter the mean dose-response curves for histamine or antigen. However, there was a small, but significant, shift of the curves to the right after cimetidine and a much larger shift to the right with chlorpheniramine, whether given alone or with cimetidine. The effect of the histamine antagonists on histamine and antigen responses was very similar and there was no difference in the pattern of response among normal subjects as compared with asthmatics or among atopic as compared with non-atopic subjects.

3. In conclusion, the same pattern of histamine receptors exists in the airways of asthmatic and normal subjects. Histamine-induced bronchoconstriction is mediated predominantly via the H1-receptors, with little, if any, contribution from the H2-receptors. Histamine appears to be an important mediator in the immediate allergic response in airways since this response is blocked by an H1-receptor antagonist.
Cardiac Function in Chronic Bronchitis: Effects of Pacing and Plasma Expansion
Authors: Valette H. , Raffestin B. , Lockhart A.
Published: August 2015

1. We have investigated left ventricular function in 25 selected patients with chronic bronchitis by use of atrial pacing and plasma volume expansion. Nine subjects had a past history of acute respiratory failure. None had either clinical or electrocardiographic signs of coronary heart disease. Paradoxical pulse was absent, since the difference between the highest and lowest systolic arterial pressure throughout the respiratory cycle was 5.4 ± 1.5 mmHg.

2. During atrial pacing, at a mean rate of 145 ±15, about 80% of the predicted maximal rate, none of the patients showed anginal pain or ventricular repolarization abnormality. Cardiac output remained unchanged compared with control values.

3. Plasma volume expansion was achieved by intravenous injection of 1 litre of gelatin over 30 min. Cardiac output, pulmonary wedge pressure and right atrial pressure rose as reported in literature for normal subjects. In four patients cardiac output did not increase although wedge pressure and right atrial pressure did; two of these four patients also had an overshoot in pulmonary wedge pressure just after atrial pacing, suggesting left ventricular dysfunction. Three out of 25 patients had high control right atrial pressures, probably in relation to impaired right ventricular function. No paradoxical pulse occurred during plasma volume expansion. Therefore competition for space in the pericardium between ventricles was unlikely.

4. Our data suggest that left ventricular dysfunction is rare in patients with chronic obstructuve pulmonary disease. There was no significant difference between subjects with and without a past history of acute respiratory failure.
Angiotensin II and Sodium as Determinants of the Agonistic-Antagonistic Balance of Saralasin's Actions
Authors: Fagard R. , Amery A. , Lijnen P.
Published: August 2015

1. To study which factors determine the balance between the antagonistic and agonistic effects of the angiotensin II analogue [Sar1,Ala8]angiotensin II (saralasin) in man, saralasin was infused in subjects on a ‘normal’ sodium intake (group 1) and during sodium restriction with appropriately elevated plasma angiotensin II levels (group 2), and in sodium-restricted subjects in whom plasma angiotensin II was suppressed by converting-enzyme inhibition with captopril (group 3).

2. The saralasin-induced increase of plasma aldosterone concentration in group 1 was different (P<0.005) from the decrease in group 2, whereas saralasin produced a significant increase of plasma aldosterone in group 3. For the three groups combined the changes of plasma aldosterone were significantly related to control angiotensin II levels, but not to the 24 h urinary sodium excretion. The data suggest that it is the rise of angiotensin II in response to the sodium restriction and not the sodium restriction per se that is associated with the antagonistic action of saralasin on the adrenal receptors.

3. On average mean intra-arterial pressure at 30 min was not affected by saralasin in group 1, had decreased in group 2 and increased (P<0.001) by 4.4 mmHg in group 3. Overall the changes of arterial pressure were significantly related to control angiotensin II, but not to the 24 h sodium excretion, suggesting that the angiotensin II levels predominantly determine the agonistic-antagonistic balance of saralasin's actions on arterial pressure.

4. Although saralasin did not affect plasma renin activity in group 1, plasma renin rose in group 2 and was reduced by 40% (P<0.001) in group 3. For the three groups together the changes of plasma renin activity were significantly related to the changes of mean arterial pressure both on single and multiple regression analyses. The changes of pressure ‘explain’, however, only a fraction of the changes of plasma renin; it is suggested that saralasin has an agonistic effect on the renal receptors involved in the direct suppression of renin by angiotensin II in low-sodium, low-angiotensin conditions and that an antagonistic effect may contribute to the saralasin-induced rise of renin during sodium restriction with appropriate angiotensin II levels.
Effect of the Converting-Enzyme Inhibitor SQ 14 225 (captopril) in Early One-Kidney, One-Clip Hypertension in the Rat
Authors: Vandongen R. , Tunney Anne , Martinez Patricia
Published: August 2015

1. Arterial plasma renin activity was significantly elevated in rats with one-kidney, one-clip hypertension of less than 3 weeks duration.

2. Intraperitoneal injection of the angiotensin-converting enzyme inhibitor SQ 14 225 (captopril) caused a dose-related decrease in systolic blood pressure in hypertensive rats. The lowest dose of captopril used (3.5 mg/kg) inhibited conversion of exogenous angiotensin I and maximally potentiated the depressor response to bradykinin, but failed to restore blood pressure to that of the normotensive controls.

3. Removal of the solitary clipped kidney also did not restore blood pressure to normal. Injection of captopril (3.5 mg/kg) 24 h after nephrectomy, when no circulating renin activity was detectable, lowered blood pressure further in hypertensive but not in similarly nephrectomized controls.

4. These results indicate that raised blood pressure in early one-kidney, one-clip hypertension in the rat cannot be entirely attributed to the renin-angioterisin system, even when plasma renin activity is significantly increased.

5. This study has also confirmed a hypotensive action of captopril in anephric rats when plasma renin activity is undetectable.
Inactive Renin in Rabbit Plasma: Effect of Frusemide
Authors: Richards H. K. , Lush D. J. , Noble A. R. , Munday K. A.
Published: August 2015

1. An inactive form of renin exists in rabbit plasma. This can be activated, and therefore measured, after acidification (pH 2.8).

2. The effect of frusemide diuresis, with replacement of volume losses, on plasma levels of active and inactive renin was studied over a 3 1/2 h time course. Plasma active renin increased during frusemide diuresis but inactive renin disappeared from the circulation. The time courses for the changes in the two forms of renin were similar.

3. The peak of the frusemide-induced changes in renal function (urine flow, sodium and potassium excretion and creatinine clearance) preceded the maximum changes in the two forms of renin by 90 min.

4. The response of plasma levels of inactive renin to physiological stimuli depends on the nature of the stimulus, as well as its duration. Some form of sodium-sensitive mechanism may control the activation of inactive renin.
Role of the Malate-Aspartate Shuttle in Renal Sodium Transport in the Rat
Authors: Ross B. , Silva Patricio , Bullock Sarah
Published: August 2015

1. Experiments were designed to establish the relationship between renal gluconeogenesis and sodium transport. Six inhibitors of gluconeogenesis, with different sites of action, were tested in the isolated perfused rat kidney in which renal function, and in particular Na+ reabsorption, was followed.

2. In kidneys from fed or starved rats specific inhibitors of gluconeogenesis neither inhibited nor stimulated Na+ reabsorption; gluconeogenesis and sodium reabsorption are therefore independent of one another under these conditions.

3. Inhibitors of transaminase or malic dehydrogenase inhibited gluconeogenesis from lactate and pyruvate respectively; the transaminase inhibitor significantly inhibited oxidation of lactate and glucose.

4. Sodium reabsorption was inhibited by a transaminase inhibitor when glucose or lactate was the sole substrate, and by inhibition of malic dehydrogenase when pyruvate was the substrate.

5. These results indicate that the malate-aspartate shuttle controls Na+ reabsorption in the intact kidney by regulating substrate oxidation (and the provision of energy) rather than by any direct involvement of gluconeogenesis in Na+ transport.
Effects of Methandienone on the Performance and Body Composition of Men Undergoing Athletic Training
Authors: Hervey G. R. , Knibbs A. V. , Burkinshaw L. , Morgan D. B. , Jones P. R. M. , Chettle D. R. , Vartsky D.
Published: August 2015

1. In a previous study of the effects of methandienone (Dianabol) on men undergoing athletic training, strength and performance increased, but not significantly more when the subjects were taking the drug than when they were taking placebo. The subjects did, however, gain more weight on the drug, with increases in total body potassium and muscle dimensions. It remained an open question whether the muscles had gained normal tissue or intracellular fluid.

2. In an attempt to distinguish between these possibilities the trial has been repeated, using as subjects seven male weight-lifters in regular training, and including measurements of total body nitrogen. As before, a dose of 100 mg of methandienone/day was given alternately with the placebo in a double-blind crossover experiment. The treatment periods lasted 6 weeks and were separated by an interval of 6 weeks. Body weight, potassium and nitrogen, muscle size, and leg performance and strength increased significantly during training on the drug, but not during the placebo period.

3. The finding of increased body nitrogen suggested that the weight gain was not only intracellular fluid. The increases in body potassium (436 ± sem 41 mmol) and nitrogen (255 ± 69 g) were too large in proportion to the weight gain (2.3 ± 0.4 kg) for this to be attributed to gain of normal muscle or other lean tissue, and imply gain of nitrogen-rich, phosphate-poor substance. Although this action of methandienone might be described as anabolic, the weight gain produced is not normal muscle.
Effect of Magnesium Deficiency and Excess on Renal Tubular Potassium Transport in the Rat
Authors: Carney S. L. , Wong N. L. M. , Dirks J. H.
Published: August 2015

1. Dietary magnesium deficiency is commonly associated with significant potassium depletion although the mechanisms responsible are unknown. Because the kidney has an important role in both magnesium and potassium homeostasis, clearance and micropuncture experiments were performed on thyroparathyroidectomized magnesium-deficient, normal and hypermagnesaemic rats to study the effect of body magnesium status on renal potassium handling.

2. Dietary magnesium restriction that reduced total-body magnesium by 30% did not alter renal potassium excretion despite a 10% reduction in total-body potassium. Graded magnesium infusions increased the fractional excretion of potassium in both magnesium-depleted and normal rats. However, the increase in the dietary depleted group was significantly less than in the control group (5-10 and then 13% compared with 7-19 and then 28% respectively). These changes in urine potassium excretion followed alterations in distal-tubule function. Parathyroid hormone did not alter potassium excretion in any of the experimental groups in contrast with its effect on magnesium excretion.

3. These data support the concept of distal tubular control of renal potassium homeostasis. The body magnesium status appears to exert some control over cellular potassium content and to alter indirectly distal-tubule potassium excretion.
Relations between Sodium Transport and Sodium Concentration in Human Erythrocytes in Health and Disease
Authors: Cumberbatch M. , Morgan D. B.
Published: August 2015

1. We have examined the inter-relationships between erythrocyte sodium content and sodium transport in a group of healthy subjects and in groups of patients with disorders known to change the sodium content of erythrocytes.

2. In the healthy subjects the sodium content of erythrocytes was inversely related to both the permeability of the erythrocyte membrane to sodium (as measured by the unidirectional, ouabain-sensitive, sodium efflux) and the total activity of the sodium pumps (as measured by the rate constant of ouabain-sensitive sodium efflux). There was a correlation between the total activity of the sodium pumps and the membrane permeability to sodium.

3. Changes in the erythrocyte sodium content were due to a decrease in the activity of the sodium pumps (as in hypokalaemia and digoxin treatment), or a decrease in the permeability of the erythrocyte membrane to sodium (as in chronic renal failure) or a reduction of both the membrane permeability and the number of sodium pumps (as in hyperthyroidism or elderly patients).

4. One interpretation of the results in the healthy subjects is that there are two components of sodium influx; one associated with the sodium pumps in what we have called ‘membrane-units’ and the other determined by the ground permeability of the membrane.

5. On the basis of this model we suggest that in the geriatric and hyperthyroid patients there is a reduction in the number of ‘membrane-units’, that in hypokalaemia and during digoxin treatment there is inhibition of the sodium-pump component of the ‘membrane-units’ and that in chronic renal failure there is a decrease in the permeability of the membrane to sodium.
The Effect of Aging on β-Adrenoceptor-Stimulated Cyclic AMP Formation in Human Lymphocytes
Authors: Kraft C. A. , Castleden C. M.
Published: August 2015

1. Responsiveness of the β-adrenoceptor adenylate cyclase system was measured in lymphocytes from healthy young and old subjects by incubating the cells with isoprenaline in the presence of a phosphodiesterase inhibitor and by measuring production of adenosine 3′:5′-cyclic monophosphate (cyclic AMP) with a competitive binding assay.

2. The two groups did not differ significantly in the levels of cyclic AMP produced or in the concentration of isoprenaline required to give half-maximal stimulation of the cells (ED50).
The Effects of Sustained Lung Inflation on the Pattern of Breathing in Man
Authors: Pearson S. B. , Heath J. R.
Published: August 2015

1. Continuous positive-pressure breathing (CPPB) at airway pressures of 0.65–1.00 kPa above ambient pressure has been used to produce a sustained inflation of the lungs of approximately 1 litre in six normal male subjects.

2. Lung inflation produced a reduction in the ventilatory response to carbon dioxide inhalation by slow rebreathing in oxygen over approximately 45 min, with a reduction in the slope of the VE/Pet,CO2 and VT/Pet,CO2 relations (Pet,CO2, = end-tidal Pco2).

3. The pattern of breathing is altered, so that for any given expired minute ventilation (VE), tidal volume (VT) is reduced with a fall in breath duration (Tt) resulting from a decrease in inspiratory time (Ti) with no change in expiratory time (Te).

4. The break point on the VT/Ti relation is lowered.
Metabolism of Antithrombin III in Cirrhosis and Carcinoma of the Liver
Authors: Chan Vivian , Lai C. L. , Chan T. K.
Published: August 2015

1. The metabolism of human antithrombin III (ATIII) was studied by using 125I-labelled tracer.

2. The plasma half-life (t0.5) was 2.71 ± 0.26 days in normal subjects and was similar in patients with cirrhosis or primary carcinoma of liver.

3. Patients with cirrhosis had low ATIII levels, decreased intravascular mass, total body mass and decreased absolute catabolic rate, suggesting decreased synthesis. The positive correlation of ATIII level with fractional catabolic rate (K10) indicated that the decreased catabolism might exert a positive inhibition on ATIII production.

4. These abnormalities were more exaggerated in patients with macronodular cirrhosis associated with hepatitis surface antigen or in those with ascites.

5. In cirrhotic patients with ascites an additional extravascular pool of ATIII was present which did not turn over at the same rate as the intravascular pool.

6. Patients with primary carcinoma of liver had moderately low ATIII, but normal intravascular mass and total body mass because of the increased plasma volume and normal absolute catabolic rate.

7. The negative correlation of ATIII levels with K10 suggested that the low levels could be due to increased catabolism or consumption.

8. One patient with disseminated malignancy and active superficial thrombophlebitis had normal ATIII metabolism.
Pubertal Induction of Sweat Gland Activity
Authors: Rees J. , Shuster S.
Published: August 2015

1. To study the difference in sweat rate between men and women the rates of cholinergic-induced sweating were measured in normal people before and after puberty and in response to androgens and anti-androgens.

2. Sweat rate in men was more than double that in women.

3. This difference did not occur in prepubertal boys and girls in whom the rate, corrected for surface area, was comparable with that in women.

4. Application or injection of androgen locally did not stimulate sweat production in the adult female.

5. Anti-androgen topically or systemically did not decrease sweat rate in men.

6. It is concluded that the rate of sweat rate in men is caused by androgen-induced gene expression at puberty and not by androgen modulation in adult life.
Changes in Renal and Urinary Kallikrein Activity by Mannitol-Induced Osmotic Diuresis
Authors: Bönner G. , Marin-Grez M. , Beck D. , Deeg M. , Gross F.
Published: August 2015

1. Osmotic diuresis was induced in male Sprague-Dawley rats by a 30% (w/v) mannitol solution injected three times at 15-min intervals. Kallikrein excretion increased for a short period after the first two injections, but, despite marked diuresis, the increment of kallikrein excretion after the second injection was less marked than after the first and no enhanced kallikrein excretion was observed after the third injection of mannitol.

2. Urinary kallikrein excretion correlated only with urinary potassium excretion. No correlation was found with either urine volume or urinary sodium excretion.

3. At the end of the osmotic diuresis kallikrein activity was significantly reduced both in the urine and in the renal cortex. At that time plasma aldosterone concentration was slightly greater in the mannitol-treated than that in the control group, but the difference did not reach statistical significance.

4. In this experiment no relationship was observed between the activity of the renal kallikrein-kinin system and the plasma aldosterone concentration.

5. The transient increase in urinary kallikrein excretion is interpreted as a wash-out effect of renal kallikrein, which is followed by a diminished kallikrein activity in urine and in renal cortex.
The Effects of Meclofenamate, Captopril and Phentolamine on Organ Blood Flow in the Conscious Rabbit
Authors: Banks R. A. , Beilin L. J.
Published: August 2015

1. Systemic and regional vascular changes were measured in conscious rabbits after intravenous sodium meclofenamate, captopril and phentolamine. These drugs were used respectively to inhibit prostaglandin synthesis and angiotensin-converting enzyme, and to block α-adrenoceptors.

2. Meclofenamate reduced renal and adrenal blood flow by 11 and 28% respectively, and doubled hepatic artery flow. The effect on renal and adrenal flow persisted in the presence of phentolamine.

3. Captopril decreased estimated peripheral resistance and increased cardiac output without changing arterial pressure. Kidney and adrenal flow increased by 70 and 21% respectively.

4. Phentolamine reduced arterial pressure and doubled flow to skeletal muscle and increased hepatic artery flow to the liver.

5. Splenic blood flow was unaffected by meclofenamate, captopril or phentolamine alone. Meclofenamate given after captopril caused a halving of splenic flow and a rise in arterial pressure; these effects were prevented by phentolamine.

6. The results point to a continuing effect of prostaglandin synthesis in maintaining blood flow to the kidney and adrenal gland independent of α-adrenoceptor activation in resting conscious rabbits. An important modulating effect of prostaglandins on sympathetic vascular tone in the spleen is suggested.
Changes in Vascular Ionic Composition at Different Stages of DOC-Salt Hypertension in the Rat
Authors: Villamil M. F. , Amorena C. , Ponce J. , Müller A. , Taquini A. C.
Published: August 2015

1. Sequential changes in the ionic composition of the aorta and skeletal muscle were followed during 1, 2 and 4–6 weeks in 30 rats given deoxycorticosterone (DOC) and salt supplemented with potassium chloride. Twenty-one rats, drinking water, were used as controls.

2. Twenty-five per cent of the test rats were hypertensive after 1 week, 60% after 2 weeks and 100% after 4–6 weeks.

3. Muscle potassium fell in all test rats by an average of 15%. In contrast, aortic potassium fell by 19% only in those rats which did not develop hypertension after 1 week.

4. Total and non-inulin sodium and water of the aorta were normal in rats which remained normotensive after 1 or 2 weeks and high in those which became hypertensive during the same period.

5. Total sodium and water content of the aorta were also high in rats which were hypertensive at 4–6 weeks. However, because of simultaneous expansion of the inulin space, non-inulin fractions were normal in this group.

6. Results suggest that vascular ionic changes participate in the pathogenesis of DOC-salt hypertension through more than a single mechanism.
Venous Plasma Histamine in Exercise- and Hyperventilation Induced Asthma in Man
Authors: Barnes P. J. , Brown M. J.
Published: August 2015

1. Venous plasma histamine was measured by a specific and sensitive radioenzymatic assay in seven male extrinsic asthmatic and six age-matched non-atopic non-asthmatic male subjects during exercise and voluntary isocapnic hyperventilation.

2. There was no change in peak expiratory flow in normal subjects with exercise or hyperventilation, but asthmatic subjects showed a 29.4 ± sem 5.8% fall after exercise and a 29.0 ± 5.4% fall after matched hyperventilation.

3. Plasma histamine was significantly higher (P < 0.05) in asthmatic (6.2 ± 0.95 nmol/l) than that in normal subjects (3.4 ± 0.61 mmol/l) and showed a significant (P < 0.01) rise (to 14.4 ± 1.83 nmol/l) during exercise in asthmatic, but not in normal subjects. This suggests that discharge of mast-cell mediators may occur during exercise in asthmatic subjects who develop exercise-induced asthma.

4. With hyperventilation there was no change in plasma histamine in either asthmatic or normal subjects, but this does not exclude the possibility that mediators may be released locally in the airways.
Role of the Brain Iso-Renin-Angiotensin System in Experimental Hypertension in Rats
Authors: Suzuki Hiromichi , Kondo Kazuoki , Handa Michiko , Saruta Takao
Published: August 2015

1. To examine the possible participation of the brain iso-renin-angiotensin system in the control of blood pressure, as well as in the regulation of plasma renin activity, saralasin and captopril were injected into the cerebral ventricles of three types of experimental hypertensive rats with different plasma renin profiles.

2. Injection of saralasin and captopril into the cerebral ventricles resulted in a significant decrease in blood pressure of two-kidney, one-clip Goldblatt hypertensive rats (11 ± 2 and 9 ± 3 mmHg respectively) and that of spontaneously hypertensive rats (13 ± 2 and 12 ± 2 mmHg respectively), but in deoxycorticosterone (DOC)-salt hypertensive rats injection of these two agents showed a significant increase in blood pressure (13 ± 2 and 12 ± 3 mmHg respectively).

3. The plasma renin activity was markedly decreased after injection of saralasin and captopril into the cerebral ventricles of two-kidney, one-clip Goldblatt hypertensive rats. Conversely, in DOC-salt hypertensive rats, the plasma renin activity was markedly increased after injection of these two agents. In spontaneously hypertensive rats these agents caused no significant change in plasma renin activity.

4. These findings suggest that the brain iso-renin-angiotensin system participates in the central regulation of blood pressure and may be responsible for modulation of the peripheral renin-angiotensin system.
Inhibition of the Renin-Angiotensin-Aldosterone System by l-Dopa with and without Inhibition of Extracerebral Dopa Decarboxylase in Man
Authors: Barbieri C. , Caldara R. , Ferrari C. , Crossignani Rosa Maria , Recchia M.
Published: August 2015

1. The present study was undertaken to investigate the possibility that central nervous system mono-aminergic pathways may play a role in the control of the renin-angiotensin-aldosterone system in man.

2. Eight normal subjects received in a randomized order placebo, l-dopa (500 mg, orally) and l-dopa (100 mg, orally) plus carbidopa (35 mg, orally) after pretreatment with carbidopa (50 mg every 6 h for four doses).

3. l-Dopa administration elicited a significant fall in plasma renin activity (PRA) (P < 0.01 at 120, 150 and 180 min) and in plasma aldosterone levels (P < 0.05 at 90, 120, 150 and 180 min); L-dopa plus carbidopa induced a decrease in PRA (P < 0.05 at 120 and 150 min, P < 0.01 at 180 min) and in plasma aldosterone concentration (P < 0.05 at 30 and 60 min, P < 0.01 at 90 and 120 min), in comparison with placebo administration; between-drugs analysis revealed no difference in the decreases in PRA and plasma aldosterone levels induced by the two regimens.

4. Since l-dopa, as well as l-dopa plus carbidopa, has been shown to augment catecholamine levels in the brain of various animal species, the present data suggest that in man PRA and plasma aldosterone concentration might be inhibited by increased central nervous system catecholamine levels.