bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphology and Function of the Dog Ileum after Mechanical Occlusion
Authors: Mirkovitch V. , Cobo F. , Robinson J. W. L. , Menge H. , Gomba Sz.
Published: August 2015

1. Complete mechanical occlusion of the ileum was produced in dogs and the loops above and below the obstruction were examined functionally and morphologically 4 or 7 days later.

2. The intraluminal pressure in the occluded loop never exceeded 8 cm water.

3. The mucosa above the obstruction secreted water and ions into the lumen in vivo, though it absorbed glucose normally. Mucosal slices also absorbed amino acids and monosaccharides normally in vitro.

4. The mucosa below the obstruction absorbed ions and glucose in vivo and non-electrolytes in vitro to a slightly smaller extent than normal intestine.

5. The morphological changes above the occlusion included shorter, plumper villi and shorter crypts, a reduction in histochemically stainable brush-border enzymes, but an increase in acid phosphatase. Below the obstruction, there was atrophy of the villi and crypts and reductions in all enzymes studied.

6. The results suggest that the mucosa above the occlusion possesses an intact and almost normal epithelial layer, but that it has been stimulated to secrete in vivo, presumably by intraluminal factors. Below the obstruction, true atrophy of the mucosa has promptly developed.
Assessment of Responsiveness to Carbon Dioxide in Patients with Chronic Airways Obstruction by Rate of Isometric Inspiratory Pressure Development
Authors: Matthews A. W. , Howell J. B. L.
Published: August 2015

1. Responsiveness to CO2 was measured in forty patients with chronic airways obstruction in terms of ventilation and rate of isometric inspiratory pressure change [(dP/dt)max.].

2. The ventilatory response was below the normal range in eighteen out of twenty-two patients with normal arterial CO2 tensions and in all of eighteen patients with CO2 retention.

3. The (dP/dt)max. response was distributed throughout the normal range in all but one of the patients with normal arterial CO2 tension. In all the patients with CO2 retention the (dP/dt)max. response was either at or below the lower limit of the normal range.

4. Although the ventilatory responses correlated significantly with FEV1 there was no such correlation for the (dP/dt)max. responses.

5. The (dP/dt)max. response showed a significant negative correlation with Pa,co2.

6. It is believed that the (dP/dt)max. response to CO2 can be used to assess central CO2 responsiveness in subjects with airways obstruction independently of mechanical factors limiting their ventilation.
Post-Heparin Plasma Lipoprotein Lipase and Hepatic Lipase in Normal Subjects and in Patients with Hypertriglyceridaemia: Correlations to Sex, Age and Various Parameters of Triglyceride Metabolism
Authors: Huttunen J. K. , Ehnholm C. , Kekki M. , Nikkilä E. A.
Published: August 2015

1. A selective immunochemical method was used to measure post-heparin plasma lipoprotein lipase and hepatic lipase activity in eighty-two normal subjects and in twenty patients with type IIb, IV or V hypertriglyceridaemia. In twenty-six normal subjects the activity of post-heparin plasma lipases was compared with the kinetic parameters of endogenous plasma triglyceride metabolism.

2. The activity of post-heparin lipoprotein lipase was significantly higher in normal females than in males, whereas the activity of hepatic lipase showed an opposite sex ratio. The activity of lipoprotein lipase decreased with age both in males and females, whereas no significant age variation was observed in the activity of hepatic lipase.

3. In normal subjects a highly significant negative correlation was present in both sexes between the activity of post-heparin plasma lipoprotein lipase and fasting serum triglyceride concentration, but not between the activity of post-heparin hepatic lipase and serum triglycerides.

4. The fractional removal rate of endogenous triglycerides was positively correlated to the activity of lipoprotein lipase but not to the activity of hepatic lipase. No relationship was found between the activities of post-heparin plasma lipases and the absolute turnover of serum triglycerides.

5. The mean activity of post-heparin plasma lipoprotein lipase was significantly lower in subjects with hyperprebetalipoproteinaemia than in normal individuals. However, many hypertriglyceridaemic patients had lipoprotein lipase within the normal range and there was no correlation between serum triglyceride concentration and the activity of post-heparin lipases.

6. All three patients with fasting chylomicronaemia had low post-heparin lipoprotein lipase activity. Several subjects with high post-heparin plasma hepatic lipase activity were present in the group with hyperprebetalipoproteinaemia, but the mean value of the hepatic lipase was not significantly different from normal.
Effect of Phenobarbitone on Plasma Lipids in Normal Subjects
Authors: Durrington P. N. , Roberts C. J. C. , Jackson Lyn , Branch R. A. , Hartog M.
Published: August 2015

1. Phenobarbitone in a dose of 180 mg daily was administered to ten normal subjects for 3 weeks. There was a significant increase in total plasma cholesterol, plasma low-density-lipoprotein cholesterol, plasma low-density-lipoprotein (LDL) triglycerides and plasma LDL protein. The increase in plasma LDL cholesterol accounted for the increase in total plasma cholesterol. There was a significant reduction in the ratio of LDL cholesterol to LDL protein.

2. No significant changes were observed in total plasma triglycerides, plasma very-low-density-lipoprotein (VLDL) triglycerides, plasma VLDL cholesterol or plasma VLDL protein.

3. Evidence that drug-metabolizing enzymes were induced by phenobarbitone was provided by an increase in antipyrine clearance. No relationship was observed between changes in plasma cholesterol and changes in antipyrine clearance. Serum γ-glutamyl transpeptidase was also increased after phenobarbitone administration, the increase being unrelated to changes in antipyrine clearance or plasma cholesterol.
Renal Haemodynamics and Plasma Renin in Patients with Essential Hypertension
Authors: Pedersen E. B. , Kornerup H. J.
Published: August 2015

1. Blood pressure, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in twenty-three patients with essential hypertension and in twenty-one control subjects. Plasma renin concentration was measured in all the hypertensive patients and in fifteen control subjects.

2. GFR and RPF were similar in the hypertensive group and in the control group, whereas the renal vascular resistance was significantly higher in the hypertensive patients. GFR and RPF decreased with increasing blood pressure in both groups. Increasing age induced a further reduction in GFR and RPF in the control subjects but not in the hypertensive patients.

3. Plasma renin concentration in the hypertensive group did not differ from that in the control subjects. The concentration was not correlated to age in either the hypertensive or normal group.

4. Plasma renin index was positively correlated to GFR and RPF and inversely correlated to filtration fraction and renal vascular resistance.

5. It is concluded that GFR and RPF depend on blood pressure in both hypertensive patients and normotensive control subjects. In contrast to the control group, the age effect was negligible in the hypertensive group. It is suggested that renin release depends on changes in renal vascular resistance in the arterioles at the glomerulus and the results support the baroreceptor theory of renin release.
The Relation between Potassium in Body Fluids and Total Body Potassium in Healthy and Diabetic Subjects
Authors: Boddy K. , Hume R. , White C. , Pack A. , King P. C. , Weyers E. , Rowan T. , Mills E.
Published: August 2015

1. The concentration of potassium in the erythrocytes and the plasma of forty-one normal subjects and twenty-five diabetic patients was measured and the results were used to calculate the total amount of potassium in the erythrocyte mass and the total amount of potassium in the plasma. The total body potassium was measured in a whole-body monitor.

2. In normal subjects a close correlation was found between total erythrocyte potassium and total body potassium and also between total plasma potassium and total body potassium.

3. The regression relation between total body potassium and total erythrocyte potassium in normal subjects was used to predict the total body potassium in diabetic patients. There was reasonable agreement between the measured and predicted total body potassium but there was poor agreement between the measured total body potassium and that predicted from the patient's height and age or height, weight and age.
Effect of Sotalol on Haemodynamics and Renin—Angiotensin—Aldosterone System in Hypertensive Patients
Authors: Verniory A. , Staroukine M. , Delwiche F. , Telerman M.
Published: August 2015

1. Twenty-three hypertensive patients were treated by sotalol, a pure beta-adrenergic receptor blocking agent. The drug produced a significant decrease of blood pressure in nineteen patients.

2. On average, cardiac index decreased but not significantly; heart rate decreased and stroke index increased significantly. Total peripheral resistance varied in both directions.

3. Sotalol determined a fall in plasma renin concentration (only significant in the high-renin group), a fall in plasma angiotensin II concentration and in urinary excretion rate of aldosterone accompanied by a rise in plasma potassium concentration.

4. The fall of blood pressure was not correlated with the decreases of renin and angiotensin II concentrations or excretion rate of aldosterone. However, in the placebo period plasma angiotensin II concentration was significantly correlated with total peripheral resistance; during sotalol treatment the variations of these two parameters seemed also to be correlated.

5. There was a poor correlation between decreases of cardiac output and of blood pressure; it was impossible to foresee the magnitude of the lowering of the blood pressure from the initial cardiac index.

6. The association of a diuretic with sotalol enhanced the hypotensive effect of the beta-receptor blocking drug, without significant increase of plasma renin and angiotensin II concentrations.
The Effect of the Porphyrogenic Compound, Hexachlorobenzene, on the Activity of Hepatic Uroporphyrinogen Decarboxylase in the Rat
Authors: Elder G. H. , Evans J. O. , Matlin S. A.
Published: August 2015

1. A new method for the measurement of uroporphyrinogen decarboxylase (EC 4.1.1.37) in rat liver homogenates, with 5-carboxyl porphyrinogen as substrate, is described.

2. The administration of a diet containing 0·3% (w/w) hexachlorobenzene produces porphyria in female Wistar rats after a delay of at least 4 weeks. The development of porphyria is accompanied by a progressive fall in hepatic uroporphyrinogen decarboxylase activity to 18% of control values after 11 weeks. The features of hexachlorobenzene porphyria are consequences of this enzyme defect.

3. Feeding with hexachlorobenzene did not lead to the accumulation of iron in the liver. It is suggested that hexachlorobenzene or a metabolite acts directly to decrease the activity of the enzyme.
The Renin—Angiotensin System and the Pathogenesis of Vascular Disease in Malignant Hypertension
Authors: Giese J.
Published: August 2015

1. The syndrome of malignant hypertension in man and animals has three fundamental components: high blood pressure, activation of the renin—angiotensin system and the rapid development of necrotizing arteriolar disease.

2. The high blood pressure can be associated with different conformations of the arteriolar microcirculation. The emergence of an arteriolar reaction pattern characterized by the formation of focal dilatations, with intervening constricted segments, is of fundamental pathophysiological importance.

3. Activation of the renin system is reflected in an increased renin secretion rate from the kidneys and an increased rate of angiotensin II generation in the pulmonary vascular bed.

4. The crucial pathogenetic process, leading eventually to severe arteriolar wall damage, is a penetration of plasmatic macromolecules into the wall of distended arteriolar segments, as observed in states of severe experimental hypertension.

5. Renin can induce vascular disease, but hypersecretion of renin is not a necessary condition for the development of hypertensive arteriolar necrosis.
Gas Exchange during Exercise in Healthy People: II. Venous Admixture
Authors: Harris E. A. , Seelye Eve R. , Whitlock R. M. L.
Published: August 2015

1. Venous admixture/cardiac output ratio (Q̇va/Q̇t) has been measured in twenty-four healthy volunteer subjects of both sexes aged 20–71 years, at rest and during the steady state of treadmill exercise at two rates of work, and breathing air and breathing oxygen.

2. With oxygen breathing, Q̇va/Q̇t was considerably less during exercise than during the time subjects were taking either normal or deep breaths of oxygen at rest, and did not significantly increase with the intensity of exercise. It is postulated that the increase in ventilation during exercise opens most or all of those alveoli which, during oxygen breathing at rest, close because of critically low ventilation/perfusion (V̇/Q̇) ratios.

3. With air breathing, Q̇va/Q̇t fell from rest to exercise (especially in older subjects), presumably due to improved ventilation of alveoli at the lung bases. With an increase in work rate Q̇va/Q̇t increased in all age groups. This increase was not due to increase in the shunt fraction (Q̇s/Q̇t), nor to limitation of diffusing capacity; it arose from an increase in V̇/Q̇ variance.

4. Equations have been derived for the prediction of normal Q̇va/Q̇t during exercise, with or without correction for the effects of increasing pulmonary capillary temperature. These effects do not materially influence the accuracy of prediction, but may be relevant to some of the interpretations. In particular, they provide a further indication that Q̇s/Q̇t probably cannot be measured by breathing oxygen at rest, even in deep breathing.
The Effect of Aluminium Hydroxide Orally on Calcium, Phosphorus and Aluminium Metabolism in Normal Subjects
Authors: Cam J. M. , Luck V. A. , Eastwood J. B. , de Wardener H. E.
Published: August 2015

1. Five normal subjects were given 100 ml of aluminium hydroxide gel per day for 28 days.

2. The phosphorus balance became more positive in one subject, less negative in two and changed from negative to positive in the other two subjects. This was accompanied by a rise in the concentration of the fasting morning plasma phosphorus. Calcium balance did not change.

3. The normal subjects absorbed 0·3–3·6 mmol of aluminium/day, which is significantly less than that absorbed by five patients with chronic renal failure, three of whom were studied before, and two after, the observations on the normal subjects had been completed.

4. In a further five normal subjects on 100 ml of aluminium hydroxide gel/day the 08.00 hours concentration of plasma phosphorus did not fall, though there was a fall at 11.00, 14.00 and 17.00 hours.
Tissue and Hepatic Subcellular Distribution of Liposomes Containing Bleomycin after Intravenous Administration to Patients with Neoplasms
Authors: Segal A. W. , Gregoriadis G. , Lavender J. P. , Tarin D. , Peters T. J.
Published: August 2015

1. Liposomes containing 111In-labelled bleomycin were injected intravenously into two patients. One patient had a hepatoma and the other had secondary adenocarcinomatous deposits in the liver.

2. The tissue distribution of 111In was determined by whole-body scanning and by measurement of the radioactivity in organs at autopsy.

3. Scans in vivo and post-mortem measurement of radioactivity indicated that liposomes accumulate predominantly in the liver, but that there is no selective uptake of liposomes by the malignant tissue.

4. The subcellular distribution of radioactivity in the liver was measured 90 min after injection by fractionation of percutaneous liver biopsies on sucrose density gradients.

5. Radioactivity within the liver was concentrated in lysosomes.

6. Electron microscopy of tissue obtained before the administration of liposomes revealed particles morphologically indistinguishable from liposomes in hepatoma cells and hepatocytes.
Regulation of the Human Pyruvate Dehydrogenase Complex
Authors: Stansbie D.
Published: August 2015

1. The pyruvate dehydrogenase complex from human heart has been partially purified and shown to be regulated by a phosphorylation-dephosphorylation cycle similar to that previously found for other mammalian tissues.

2. Incubation of the complex with ATP (2 mmol/l) led to its inactivation associated with the concomitant incorporation into the protein of 32P from the terminal phosphate group of the ATP. Pyruvate, ADP, thiamin pyrophosphate and dichloroacetate diminished the rate of inactivation by ATP.

3. Pyruvate dehydrogenase phosphatase from human heart requires Mg2+ for activity and is sensitive to Ca2+ at concentrations of a few μmol/l. Similar ionic requirements of the skeletal muscle phosphatase have been demonstrated in a crude tissue extract.

4. The activity of pyruvate dehydrogenase in human adipose tissue was less than 10% of typical values in rats. This could be due to the high level of dietary fat consumed by humans, which is known to repress the enzyme activity in rats.
The Safety Assessment in the Dog of a Charcoal Haemoperfusion Column
Authors: Kolthammer J. C. , Watson P. A. , Lang S. , Fennimore J.
Published: August 2015

1. The safety of a carbon haemoperfusion column, Haemocol, has been studied in beagle dogs.

2. Only minor changes in physiology, haematology and plasma chemistry were detected, except those associated with an improvement in clinical status.

3. It is concluded that haemoperfusion through this column is a safe and simple procedure, which merits evaluation in the treatment of severe drug overdose in man.
Accelerated Hypertension in the Rat: Relation between Renin, Renal Vascular Lesions, Salt Intake and Blood Pressure
Authors: Chusilp Sauwaluck , Hua A. S. P. , Kincaid-Smith Priscilla
Published: August 2015

1. Complete ligation of the aorta between the origins of the two renal arteries in the rat produces a predictable form of accelerated hypertension. Changes in the blood pressure, plasma renin activity and renal histological lesions have been studied.

2. Group 1 rats and their control group (group 2) received tap water, and group 3 and its control group (group 4) received sodium chloride solution (0·154 mol/l) in place of tap water, for 4 weeks before aortic ligation. In the experimental groups 1 and 3, complete ligation was carried out. In groups 2 and 4 the aorta and renal arteries were exposed, but not ligated. Interlobular artery lesions were studied on a blind basis and graded 0–4 according to severity.

3. Groups 1 and 3 developed severe hypertension. In group 1 the raised mean arterial pressure showed a significant correlation with increased plasma renin activity. Both mean arterial pressure and plasma renin activity also showed a significant correlation with changes in interlobular arteries. In group 3 the raised mean arterial blood pressure did not show a significant correlation with the depressed plasma renin activity, or with changes in interlobular arteries. A significant correlation was, however, found between plasma renin activity and interlobular artery lesions in group 3.

4. These results suggest that the renin-angiotensin system may influence renal vascular lesions through some mechanism independent of the blood pressure.
The Pathogenesis of Hypertensive Vascular Changes in the Rat: Microscopic and Ultrastructural Correlation in Vivo
Authors: Hobbs J. B. , Chusilp S. , Hua A. , Kincaid-Smith P. , McIver M. A.
Published: August 2015

1. This study describes the changes observed in the rat microcirculation in vivo in the transparent tissue chamber of the rat back, during the florid hypertension produced by ligation of the rat aorta between both renal arteries.

2. Besides providing a new model for analysis of the action of therapeutic agents in hypertension, direct evidence of the variation in blood flow in hypertension is discussed. Fixation of the chamber tissues allows direct ultrastructural correlation with the altered function of particular vessels observed and recorded cinemicroscopically in vivo.
Inter-Relationship between Autoregulation of Glomerular Filtration Rate, Tubuloglomerular Feedback and Juxtaglomerular Renin Activity in Normotensive and Hypertensive Rats
Authors: Schnermann J. , Ploth D. W. , Dahlheim H.
Published: August 2015

1. Reduction of renal perfusion pressure from 133 mmHg to 117 mmHg in control rats did not induce a significant change of kidney glomerular filtration rate (GFR) or nephron GFR determined in distal tubules. In contrast, nephron GFR measured in proximal tubular segments (NGFR-P) fell significantly.

2. Qualitatively the same response of filtration rate to changes of arterial blood pressure was found in the chronically clipped kidneys of Goldblatt hypertensive rats after acute removal of the clip.

3. In contrast, autoregulation of kidney GFR, NGFR-D and NGFR-P was abolished in the contralateral kidneys of Goldblatt hypertensive rats.

4. Microperfusion studies showed that tubuloglomerular feedback regulation of NGFR was present in the renin-rich ischaemic kidneys of Goldblatt rats after removal of the constricting clip, but greatly attenuated in the renin-depleted contralateral kidneys.

5. These data indicate that tubuloglomerular feedback participates in establishing renal autoregulation, possibly by mediation of the renin-angiotensin system.
The Role of Sodium Retention in Goldblatt 2-Kidney Hypertension in the Rat
Authors: Thurston H. , Swales J. D.
Published: August 2015

1. Infusion of angiotensin II antagonist failed to restore the blood pressure of short-term Goldblatt 2-kidney hypertensive rats to normal levels before and after sodium restriction.

2. The blood pressure of both normal and sodium-restricted Goldblatt 2-hypertensive rats remained elevated 6 h after bilateral nephrectomy.

3. The residual hypertension found during antagonist infusion and after bilateral nephrectomy is not maintained by the renin—angiotensin system or sodium retention.
Cardiac Output Changes during Experimental Renal Hypertension in the Rabbit
Authors: Fletcher P. J. , Korner P. I. , Angus J. A. , Oliver J. R.
Published: August 2015

1. The haemodynamic changes during the development of hypertension in rabbits have been studied for 1 week before and 4–5 weeks after sham-operation (thirteen rabbits) or bilateral renal cellophan wrapping (thirteen rabbits), Doppler flowmeters being used to measure cardiac output.

2. There was a significant but transient rise in cardiac output on post-operative day 4 in six of thirteen sham-operated rabbits and six of thirteen renal-wrap rabbits before development of hypertension. Both groups showed the same rise in mean cardiac output of 10%. The rise in cardiac output was more transient than in other species, and was not essential for subsequent development of hypertension.
Delayed Onset and Reduced Severity of Adrenal-Compression Hypertension in Rats Treated with Digitoxin
Authors: Hall C. E. , Ayachi S. , Hall O.
Published: August 2015

1. Bilateral compression of adrenal glands combined with unilateral nephrectomy and followed by imposition of a high sodium chloride intake caused severe hypertension in all rats, accompanied by enlargement of the heart, kidneys and adrenal glands, atrophy of the thymus and severe nephrosclerosis.

2. Digitoxin treatment delayed the onset, reduced the incidence and ameliorated the magnitude of the hypertensive response in such rats; it also reduced the degree of cardiac hypertrophy, the severity of nephrosclerosis and completely prevented enlargement of the adrenals and kidneys or atrophy of the thymus.
Follow-up of Renin in Essential Hypertension
Authors: Birkenhäger W. H. , Kho T. L. , Schalekamp M. A. , Zaal G. A. , Wester A. , De Leeuw P.W. , Vandongen R. , Fawzi-Meninger T. D.
Published: August 2015

1. Twenty-three subjects with essential hypertension were followed for a period of up to 7 years. They were untreated during the investigations.

2. Plasma renin concentration was found to decrease temporarily in some subjects. The ultimate change was a gradual rise. In those subjects who suffered myocardial infarction renin tended to rise more sharply.

3. A relationship was established with the rise in renal vascular resistance, which almost invariably occurred over the years.
Renin—angiotensin and Kallikrein—kinin Systems in Sodium Homeostasis and Hypertension in Rats
Authors: Johnston C. I. , Matthews P. G. , Dax E.
Published: August 2015

1. Urinary kallikrein excretion was measured in rats by an enzyme kinetic method employing radioimmunoassay of generated bradykinin.

2. Rats given a sodium load (NaCl solution, 20 g/l, to drink) for 28 days showed acute and prolonged significant falls in urinary kallikrein excretion associated with suppression of plasma renin and angiotensin.

3. Conversely sodium-depleted rats showed increases in urinary kallikrein excretion, associated with rises in plasma renin and angiotensin.

4. A close and significant direct relation between plasma renin activity and urinary kallikrein excretion was demonstrated.

5. The diuresis and natriuresis induced by frusemide in rats was associated with increased urinary kallikrein excretion and acute rises in plasma renin.

6. In chronic renal hypertensive rats urinary kallikrein excretion was increased only in the animals with two-kidney Goldblatt hypertension. This group was also the only group that demonstrated a significant rise in plasma renin activity.
Anti-hypertensive Lipid from Tissue Culture of Renomedullary Interstitial Cells of the Rat
Authors: Muirhead E. E. , Rightsel W. A. , Leach B. E. , Byers L. W. , Pitcock J. A. , Brooks B.
Published: August 2015

1. Allogenic transplants of cultured renomedullary interstitial cells exert a powerful anti-hypertensive action. The blood pressure of hypertensive animals usually drops slowly over 8–12 h whereas the pulse is unchanged or reduced.

2. Lipids derived from the cultured cells exert a similar anti-hypertensive action.

3. The anti-hypertensive action of transplanted cultured cells almost certainly results from the secretion of a substance(s) that acts in the manner of a hormone. The tissue culture lipid is a prime candidate hormone.

4. The relationship of the kidney to the hypertensive state is considered to entail pro- and antihypertensive actions. The pro-hypertensive actions include (a) activation of the renal pressor system (mainly renin—angiotensin), (b) failure to prevent sodium and fluid overloading because of either an injured or absent kidney or the excessive action of mineralocorticoids (mainly aldosterone). The antihypertensive actions of the kidney include (a) the relief of sodium and fluid overloading through diuresis—natriuresis and (b) the action of the renomedullary interstitial cell hormone (the antihypertensive renomedullary hormone).
Deoxycorticosterone Hypertension in the Pig
Authors: Terris J. M. , Berecek K. H. , Cohen E. L. , Stanley J. C. , Whitehouse W. M. , Bohr D. F.
Published: August 2015

1. Deoxycorticosterone acetate (DOCA) implantation (100 mg/kg) caused mean arterial pressure to rise in 5–10 days from control pressures of 100–115 mmHg to stable hypertensive valnes of 140–160 mmHg in approximately 1 month. In six of seven pigs elevations of mean arterial pressure were entirely the result of increased total peripheral resistance.

2. Single implants maintained serum DOCA at approximately ten times normal concentration for up to 90 days.

3. Moderate but variable decreases in serum aldosterone followed implantation.

4. Hypokalaemia, polydipsia and suppressed plasma renin activity were evident by the fifth post-implantation day and persisted thereafter. No consistent change occurred in serum sodium.

5. Noradrenaline or angiotensin caused increases in total peripheral resistance at lower threshold infusion rates in hypertensive pigs compared with control animals.

6. In isolated, perfused hind-limb preparations, hypertensive vascular beds were characterized by both functional (increased vascular smooth muscle sensitivity) and structural (elevated resistance of maximally dilated vascular bed) changes. ‘Protection’ from increased arterial wall stresses in hypertensive pigs prevented structural, but not functional, alterations.
Increased Renal Sensitivity to Aldosterone in the Potassium-Loaded Rat
Authors: Adam W. R. , Funder J. W.
Published: August 2015

1. The renal response to aldosterone (urinary sodium and potassium excretion) was determined in adrenalectomized rats previously fed either a high potassium diet or a control diet. High K+ rats showed an enhanced response to aldosterone at all doses tested.

2. This enhanced response to aldosterone required the presence of the adrenal glands during the induction period, could be suppressed by a high sodium intake, but could not be induced by a low sodium diet.

3. No difference between high K+ and control rats could be detected in renal mineralocorticoid receptors, assessed by both in vivo and in vitro binding of tritiated aldosterone.

4. The method of the induction, and the mechanism of the enhanced response, remain to be defined.
Cardiac Reflexes Conducted by Vagal Afferents in Normotensive and Renal Hypertensive Dogs
Authors: Kezdi P.
Published: August 2015

1. The renal sympathetic reflex responses to transient balloon occlusion of the descending aorta (systemic baroreceptor activation) and the ascending aorta (cardiac stretch-receptor activation) have been studied together with blood pressure increases after successive cutting of carotid sinus, aortic and vagus nerves in acute experiments in the dog.

2. Results from these experiments provide evidence for cardiac vagal afferent participation in the tonic regulation of systemic blood pressure.

3. In other experiments the reflex pressure-response curve of the isolated gracilis muscle at constant flow to transient ascending aorta occlusion was measured. This curve was moved to the right in renal hypertensive dogs as compared with normotensive dogs. The threshold response of left ventricular vagal afferent nerves was shifted to higher left ventricular pressure in the former.

3. These findings indicate resetting of ventricular receptors in hypertensive animals.
Baroreflex Control of Coronary Conductance in Normotensive and Renal Hypertensive Conscious Dogs with Complete Heart Block
Authors: White S. W. , Porges W. L. , Reid J. V. O. , Bhagat C. I.
Published: August 2015

1. The autonomic and local control of the circumflex coronary bed evoked through acute rises in aortic pressure (aortic balloon inflation) was analysed in conscious, normotensive and hypertensive dogs in complete heart block with ventricles paced at 100 beats/min.

2. In normotensive dogs there was an initial rise (6–12 s) in circumflex conductance preceding a fall in conductance as aortic pressure increased and was sustained. The initial rise, but not the later fall, in circumflex conductance was partly due to a cholino-receptor and partly due to α-adrenoreceptor mechanisms. Local constrictor mechanisms were responsible for the later fall in conductance.

3. The initial cholinoreceptor component of the rise in circumflex conductance is initiated through arterial baroreflex mechanisms.

4. The initial autonomic mechanisms regulating circumflex conductance appear to be absent in renal hypertension.

5. The absence of the transient autonomic rise in circumflex flow and conductance in response to rapid elevations in aortic pressure in certain forms of hypertension, e.g. during tachyarrhythmias and behavioural disturbances, may result in myocardial ischaemia when it is least appropriate.
Valsalva Vasoconstrictor Reflex in Human Hypertension and after β-Adrenoreceptor Blockade in Conscious Rabbits
Authors: Korner P. I. , Blombery P. A. , Bobik A. , Tonkin A. M. , Uther J. B.
Published: August 2015

1. A Valsalva-like manoeuvre was used to elicit graded rises in total peripheral resistance (TPR) in conscious rabbits. The rises were reflex and mediated through sympathetic constrictors. Propranolol infused at different rates reaching plasma concentrations up to 240 (sem 33) ng/ml had no effect on this reflex but reduced mean arterial pressure. However, the response was attenuated by clonidine in a dose-dependent manner.

2. Valsalva manoeuvres were used to elicit graded sympathetically mediated rises in TPR index in twenty-nine subjects with mean arterial pressure ranging from 75 to 165 mmHg. Absolute sensitivity of the constrictor response increased with rising resting TPR index, resulting in some enhancement of constrictor responses in the hypertensive subjects. It seems likely that non-autonomic factors (e.g. vessel structure) rather than hyperactive neural constrictor effects are involved in the enhanced constrictor responses in essential hypertension.
Effect of Angiotensin II on Noradrenaline Content in the Rat Hypothalamus
Authors: Iijima M. , Kitamura Y. , Yamamoto N. , Kawamura H. , Yasugi T. , Hatano M.
Published: August 2015

1. Intravenous administration of angiotensin II reduced the adrenaline content, increased the catechol-O-methyltransferase activity, and decreased the monoamine oxidase activity of the rat hypothalamus.

2. Intraventricularly administered angiotensin II reduced the noradrenaline content to a smaller extent.

3. The change produced by intravenous administration of angiotensin might be indirectly caused by a response to angiotensin.
Neural and Non-Neural Mechanisms in Spontaneous Hypertension
Authors: Yamori Y.
Published: August 2015

1. The pathogenesis of hypertension in spontaneously hypertensive rats (SHR) is considered to consist of neurogenic and non-neurogenic factors, both of which contribute to initiation and maintenance mechanisms.

2. Neurogenic factors have been demonstrated by the destruction of the central nervous system, sympathectomy, recording of sympathetic discharge, hind-limb perfusion and study of noradrenaline. These factors are mainly involved in the initiation of hypertension, and they appear to diminish in importance after the establishment of hypertension, as indicated by the noradrenaline-turnover study.

3. The non-neurogenic factors have been demonstrated haemodynamically by increased peripheral vascular resistance remaining even after sympathectomy. They have also been demonstrated histologically by the narrowing of resistance arteries with medial hyperplasia or hypertrophy. These factors appear to participate in maintenance mechanisms.

4. Increased incorporation of labelled amino acid into non-collagenous and collagenous protein of the arterial walls precedes medial hypertrophy and hypertensive arteriosclerosis. It seems to play a role therefore both during neurogenic initiation and later non-neurogenic maintenance of blood pressure.

5. Non-collagenous protein metabolism of arterial walls is increased in young SHR, and it is partly dependent on neural innervation as detected by surgical or pharmacological sympathectomy. It indicates a close linkage between neurological and structural changes in the initiation of spontaneous hypertension.
Sympathotonia in Primary Hypertension and in a Caricature Resembling Dysautonomia
Authors: Dequattro V. , Campese V. , Miura Y. , Esler M.
Published: August 2015

1. Plasma catecholamines and adrenergic correlates of cardiac function were compared in young men with borderline hypertension, classified according to renin status (group 1). Plasma catecholamines were increased and cardiac pre-ejection periods were shortened in ‘high’-renin patients.

2. Plasma catecholamines were raised in 70% of ‘high’-renin patients with primary hypertension (group 2), were related directly with age in normotensive females and were related inversely with catecholamine responses to postural stress in both normotensive and hypertensive subjects (P < 0·01).

3. The raised catecholamines of four ‘high’-renin patients with pronounced features of sympathetic nerve activity-caricatures were elevated further during hypertensive periods. Mean arterial blood pressures were reduced 20–30% after either α- or β-receptor blockade. Catecholamines were reduced after β-receptor blockade.

4. There appears to be a spectrum of neurogenic ‘gain’ in primary hypertension; it is suppressed in ‘low’-renin hypertension, directly related to blood pressure in ‘normal’-renin hypertension, increased in ‘high’-renin hypertension and achieves a maximum in caricatures. Neurogenic factors seem to be important in the cause and maintenance of ‘high’- and ‘normal’-renin hypertension respectively. The caricatures may be examples of a severe form of hypothalamic stimulation.
Plasma Noradrenaline and Renovascular Hypertension in the Rat
Authors: Reid J. L. , Dargie H. J. , Franklin S. S. , Fraser Beverly
Published: August 2015

1. Plasma noradrenaline was measured in groups of rats up to 4 weeks after application of a renal artery clip.

2. When renal artery clipping was accompanied by contralateral nephrectomy (one-kidney model) plasma noradrenaline was significantly higher in hypertensive rats than in sham-operated control rats at 7, 14 and 28 days.

3. Plasma noradrenaline was not altered at any time examined in the two-kidney model (unilateral clip and contralateral kidney left in situ).

4. Neurogenic mechanisms mediated by the peripheral sympathetic nervous system appear to participate in the development of one-kidney renovascular hypertension, but do not play a significant role in the two-kidney model.
Interaction of Angiotensin II with Catecholamines in the Circulation of the Dog and Cat
Authors: Ng K. K. F. , Duffy S. , Louis W. J. , Doyle A. E.
Published: August 2015

1. The blood-bathed organ technique was employed to study the effects of angiotensin II and catecholamines on an isolated everted rat aorta bathed in the extracorporeal circulating blood of adult dogs and cats.

2. When the injections were made into the bathing blood close to the everted rat aorta, angiotensin II was half as potent as adrenaline or noradrenaline on a molar basis.

3. After intravenous injections, the vasoconstrictor potency of angiotensin was twenty times that of adrenaline or noradrenaline on the everted rat aorta. The increase in potency was due to the interaction of angiotensin II with catecholamines on the preparation.

4. Intravenous phenoxybenzamine abolished the potentiated vasoconstrictor effect of angiotensin II on the blood-bathed everted rat aorta, but it did not abolish the pressor effect of angiotensin II on the cardiovascular system of the animals. The results suggest that catecholamines released into the circulating blood by intravenous angiotensin II do not play an important role in the pressor effect of angiotensin II.
Catecholamines, Blood Pressure, Renin and Myocardial Function in the Spontaneously Hypertensive Rat
Authors: Oparil Suzanne , Erinoff Lynda , Cutilletta A.
Published: August 2015

1. Neither nerve-growth-factor antiserum (NGFAS) administered subcutaneously nor 6-hydroxydopamine administered intraventricularly to immature spontaneously hypertensive rats (SHR) inhibited the development of the hypertensive syndrome. In contrast, NGFAS did not affect blood pressure in normotensive Kyoto/Wistar rats.

2. Peripheral vascular resistance was increased and cardiac index decreased in both NGFAS and 6-hydroxydopamine-treated SHR despite preservation of normal blood pressure.

3. NGFAS treatment did not influence the development of left ventricular hypertrophy in SHR, despite the lowering of blood pressure. In contrast, 6-hydroxydopamine caused an attenuation in the development of left ventricular hypertrophy.

4. Indices of left ventricular contractility were depressed by NGFAS treatment but not by 6-hydroxydopamine.

5. Plasma renin activity was unaffected by NGFAS treatment and increased by 6-hydroxydopamine.
Haemodynamic Long-Term Effects of β-Receptor-Blocking Agents in Hypertension: A Comparison between Alprenolol, Atenolol, Metoprolol and Timolol
Authors: Lund-Johansen P. , Ohm O. J.
Published: August 2015

1. Oxygen consumption and central haemodynamics were recorded at rest and during exercise in fifty-one men with essential hypertension (W.H.O. stage I) and repeated after 1 year on a single drug: alprenolol (n = 10), atenolol (13) metoprolol (12) and timolol (16).

2. Mean arterial pressure was significantly reduced in all groups at rest (11–18%) and during exercise (5–11%). Heart rate was significantly reduced in all groups (20–28%) at rest and (17–26%) during exercise. Owing to increase in supine resting and exercise stroke volume in the alprenolol and atenolol group, cardiac index decreased less than heart rate-in contrast to the timolol group where cardiac index was decreased 26–32%. The calculated post-treatment total peripheral resistance was significantly increased at rest and during exercise in the timolol group. In the other groups the total peripheral resistance was significantly increased at rest when sitting, but not at rest when supine and during exercise.

3. It is concluded that the major haemodynamic changes induced in subjects with moderate and mild essential hypertension by these different β-receptor blockers are the same, but that minor differences exist with respect to effect upon stroke volume and total peripheral resistance.
Clinical Evaluation of Atenolol in Hypertension
Authors: Hansson L. , Karlberg B. E. , Åberg H. , Westerlund A. , Henningsen N. C. , Jameson S.
Published: August 2015

1. Atenolol (ICI 66.082, Tenormin) is a new β-adrenoreceptor-blocking agent, devoid of intrinsic sympathomimetic and membrane-stabilizing properties. It does not cross the blood—brain barrier.

2. Atenolol given to hypertensive patients in initial open trials reduced arterial blood pressure significantly.

3. A double-blind comparison between atenolol and placebo in forty-five patients with essential hypertension demonstrated that atenolol gave a statistically significant reduction of blood pressure (Δ 28/15 mmHg, P < 0·005).

4. The optimum anti-hypertensive dose of atenolol in patients with mild to moderately severe essential hypertension was 200 mg daily.

5. Atenolol was compared with propranolol in thirty patients with essential hypertension. No statistically significant differences of anti-hypertensive effect were observed between the two drugs.

6. Long-term results (up to 2 years) in 117 hypertensive patients indicate that drug tolerance is good. No serious toxic effects were observed.

7. In four of twelve hypertensive patients with obstructive airways disease atenolol had to be withdrawn owing to deterioration of ventilatory function.
A Controlled Study on the Anti-Hypertensive Effect of a new β-Adrenoreceptor-Blocking Drug, Metoprolol, in Combination with Chlorthalidone
Authors: Jäättelä A. , Pyörälä K.
Published: August 2015

1. A double-blind cross-over evaluation of the anti-hypertensive effect of metoprolol vs placebo was carried out in a series of twenty-three patients with mild or moderate essential hypertension who were receiving 25 mg of chlorthalidone daily as their basic treatment. An individually determined dose of metoprolol (75–300 mg) was used.

2. Metoprolol, as compared with placebo, produced a statistically significant reduction of blood pressure, both in supine and standing positions.

3. During the double-blind cross-over study mild side effects were more common at the beginning of metoprolol/chlorthalidone treatment than during placebo/chlorthalidone, but these tended to diminish or disappear with time.

4. Metoprolol in combination with chlorthalidone appears to be an effective and well-tolerated treatment for mild and moderate hypertension in patients not responding to chlorthalidone alone.
Clinical and Haemodynamic Study of Atenolol (Tenormin) in Essential Hypertension
Authors: Jensen H. Æ. , Rasmussen K. , Mosbæk N.
Published: August 2015

1. The β1-adrenoreceptor-blocking agent atenolol was studied in the treatment of twelve out-patients with essential hypertension.

2. With a mean dose of 110 mg of atenolol daily (range 75–200 mg/day) we observed a pronounced decrease in blood pressure.

3. Only minimal side effects were seen.

4. Cardiac output decreased from 4·6 to 3·4 l/min during treatment. This decrease did not correlate with the decrease in blood pressure but correlated well with the changes in calculated total peripheral resistance.
Comparison of Metoprolol and Propranolol in Modification of Haemodynamic and Renin-Aldosterone Responses to Tilting in Humans
Authors: Viol G. W. , Smith E. K. M. , Fitzgerald J. D.
Published: August 2015

1. Acute oral administration of metoprolol and propranolol to ten normal males resulted in equal reduction in heart rate both supine and after passive tilting to 60°.

2. Tilted systolic blood pressure was reduced by both agents but metoprolol alone reduced supine systolic blood pressure.

3. Tilted but not supine diastolic blood pressure was reduced by both agents.

4. Metoprolol and propranolol both reduced the rise in plasma renin activity induced by tilting.

5. No effect of tilting was observed on plasma aldosterone.
Differential Effects of Acute and Chronic β-Adrenoreceptor Blockade on Blood Pressure and the Renin—Angiotensin—Aldosterone System in Essential Hypertension
Authors: Kolloch R. , Stumpe K. O. , Vetter H. , Gramann W. , Krück F.
Published: August 2015

1. Serial measurements of plasma renin activity (PRA), plasma aldosterone concentration (PA) and blood pressure were performed overnight in patients with borderline (group 1) and sustained essential hypertension (group 2) before and after acute and chronic administration of either propranolol or pindolol.

2. Group 1 patients exhibited a typical rhythm of recumbent PRA with low values before midnight and large increases early in the morning.

3. In contrast, no rhythm and very low PRA values were observed in patients of group 2. Blood pressure was higher in group 2 than in group 1. There was a significant correlation between the hyporeninaemic and hypotensive effect of either acute (r = 0·79) or chronic (r = 0·4) β-receptor blockade.

4. In group 1, after β-receptor blockade the day—night profile of renin was similar to that observed in group 2 before treatment. Thus, in this latter subgroup, low-renin profiles might reflect reduced β-adrenoreceptor activity.

5. Plasma aldosterone was lower in group 2 but appeared to be inappropriately high relative to renin.

6. The data suggest that in hypertensive patients classified according to their blood pressure and recumbent PRA profiles a significant relationship exists between changes in PRA and arterial pressure. Thus patients with high PRA respond better to treatment than patients with low renin. We conclude that in the patients studied sympathetic nervous system activity mainly determined renin values as well as anti-hypertensive effectiveness of the β-blocking drugs.
β-Receptor-Blockade Hypotension and the Central Nervous System
Authors: Lewis P. J.
Published: August 2015

1. Intravenous infusion of propranolol (3·86 μmol h—1 kg—1) for 2 h lowered arterial pressure in the conscious rabbit whereas similar infusions of practolol (37·6 μmol h—1 kg—1) did not.

2. The fall in blood pressure produced by propranolol was accompanied by a decrease in splanchnic nerve activity. Practolol did not change splanchnic nerve activity.

3. A centrally mediated decrease in sympathetic nervous activity makes an important contribution to the hypotensive action of propranolol in the rabbit. This effect is not shown by practolol.
Within-Patient Comparisons between Different Anti-Hypertensive Drugs
Authors: Harvald B.
Published: August 2015

1. By substituting one anti-hypertensive drug for the other in a panel of hypertensive patients equipotent doses have been determined.

2. Thus 40 mg of propranolol is equivalent to 4·5 mg of pindolol, 98 mg of practolol, 128 mg of alprenolol, 49 mg of metoprolol, 42 mg of tolamolol and 4·4 mg of timolol.

3. Bendorfluazide (10 mg) is eqivalent to 1·6 mg of bumetanide, 20 mg of chlorthalidone, 35 mg of mefruside and 3·5 mg of amiloride together with 35 mg of hydrochlorthiazide.

4. Methyldopa (250 mg) is equivalent to 6 0 mg of debrisoquine and 0·5 mg of St 600 (Boehringer), which is a clonidine-like substituted imidazoline.