bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Natriuretic Activity in the Plasma of Hypervolaemic Rats
Authors: Veress A. T. , Milojevic S. , Sonnenberg H.
Published: August 2015

1. Plasma from hypervolaemic rats was fractionated on a G-200 Sephadex column. In addition to three different protein peaks, a fourth non-protein fraction was obtained. Each of the four peaks was desalted, freeze-dried, reconstituted and injected into normal anaesthetized rats. Significant natriuretic responses resulted, from injection, of the middle protein peak and of the small-molecular-weight peak. It was concluded that a natriuretic humoral factor was present in the blood of hypervolaemic rats, and that this factor was of low molecular weight but normally occurred bound to plasma protein.

2. The renal response to injection of non-protein fraction, obtained from either hypervolaemic donors or from iso- or hypo-volaemic donors, was compared in two groups of bioassay rats to test whether the natriuretic factor was present only in plasma of the blood-volume-expanded animals. Both types of reconstituted fraction caused diuresis, natriuresis and kaliuresis in bioassay animals. Only the natriuretic response was statistically greater when the fraction obtained from hypervolaemic plasma was used. In addition to non-specific increase in fluid and ion excretion, possibly due to the extraction and/or methodological procedures, these results demonstrate that blood-volume expansion releases a humoral natriuretic factor into plasma. Since there were no increases in filtration rate, the factor specifically inhibited tubular sodium re-absorption.

3. To determine the maximum possible effect of the non-protein factor, the dose given to bioassay rats was tripled. There was no further increase in sodium excretion, indicating that the effect was quantitatively limited and suggesting that the physiological importance of natriuretic hormone lies in long-term regulation of body-fluid balance.
Forearm Glucose Uptake in Cirrhosis and Its Relationship to Glucose Tolerance
Authors: Leatherdale B. A. , Chase R. A. , Rogers J. , Alberti K. G. M. M. , Davies P. , Record C. O.
Published: August 2015

1. Oral glucose-tolerance tests (100 g) were carried out in six patients with stable well-compensated cryptogenic cirrhosis and in 12 control subjects.

2. In confirmation of previous studies, patients with cirrhosis had high post-glucose serum insulin levels and were glucose intolerant (mean incremental glucose area 954 ± 186 compared with 482 ± 35 mmol 3 h−11−1 in controls; P<0.05)

3. Forearm arteriovenous differences of glucose and forearm blood flows were measured to estimate the proportion of the glucose load metabolized in peripheral tissues. Values in cirrhotic patients and control subjects (5614 ± 1630 compared with 5344 ± 672 μmol of glucose min−11−1 of forearm in 3 h) were similar despite higher glucose levels and sustained high insulin levels in the cirrhotic patients.

4. Peak lactate concentrations after glucose were of similar magnitude in the two groups (0.66 ± 0.12 compared with 0.62 ± 0.75 mmol/l) but in the patients with cirrhosis the peak occurred later and was more sustained.

5. The glucose intolerance of cirrhosis is primarily due to impaired hepatic retention of the glucose load. Insulin resistance in peripheral tissues-5-also be important since the higher insulin concentrations found in cirrhotic patients failed to enhance peripheral glucose uptake.
Importance of the Cyclic AMP Concentration for the Rate of Lipolysis in Human Adipose Tissue
Authors: Arner P. , Östman J.
Published: August 2015

1. The activation of lipolysis on incubation of human subcutaneous adipose tissue was examined in terms of the relationship between the release of glycerol and the concentration of tissue cyclic AMP.

2. A strong positive correlation was obtained between the maximum concentration of cyclic AMP and the rate of glycerol release in the presence of noradrenaline (r = 0.9), whereas, in the basal state, these two parameters were only weakly correlated (r = 0.45).

3. It appears that the noradrenaline-induced rate of lipolysis depends upon the maximal concentration of cyclic AMP that is present in human adipose tissue.
Myocardial Electrical Instability after Abrupt Withdrawal of Long-Term Administration of Propranolol to Guinea Pigs
Authors: Dennis S. C. , Manning A. S. , Hearse D. J. , Coltart D. J.
Published: August 2015

1. Abrupt termination of chronic propranolol therapy has been suggested to cause a ‘rebound’ phenomenon. To investigate this possibility guinea pigs were given propranolol orally for 21 days.

2. At various times over a 10 day period after the last dose hearts were removed and subjected to aerobic perfusion, ischaemia and reperfusion. Rhythm disturbances were measured and compared with corresponding values in control hearts from the control untreated animals.

3. Three to 6 days after termination of drug administration a pronounced increase in myocardial electrical instability was observed. During pre-ischaemic aerobic perfusion the incidence of arrhythmias was increased and during reperfusion the incidence of ventricular fibrillation rose dramatically.
Renin Precursor and Its Activation Mechanism in Hog Kidney
Authors: Murakami Kazuo , Takahashi Saori , Hirose Shigehisa , Takii Yukio , Inagami Tadashi
Published: August 2015

1. A completely inactive renin was isolated from hog kidney extract by affinity chromatography on pepstatin-aminohexyl-Sepharose and on an Affi-Gel Blue column.

2. This inactive renin had a molecular weight of 43 000 ± 1500 as determined by gel filtration on Ultrogel AcA 44. Upon activation with trypsin, its molecular weight fell to 41 000 ± 1400.

3. The inactive renin lacked the ability to bind renin-binding substance whereas trypsin-activated renin was able to bind the renin-binding protein and to form high-molecular-weight renin.

4. Chymotrypsin as well as trypsin could activate the inactive renin although less effectively.

5. The active renins generated from the inactive renin by the action of different proteolytic enzymes differed in their net charge, reflecting the specificities of the proteases used; the isoelectric points of the native, the trypsin-activated and the chymotrypsin-activated forms of renin occurred at pH 5.3, 5.1 and 4.8 respectively.
Elevation of Plasma Neurotensin in the Dumping Syndrome
Authors: Blackburn A. M. , Christofides N. D. , Ghatei M. A. , Sarson D. L. , Ebeid F. H. , Ralphs D. N. L. , Bloom S. R.
Published: August 2015

1. The pathophysiology of the dumping syndrome is poorly understood. Plasma levels of four small intestinal hormones have been measured after an oral glucose provocation test in 19 patients with dumping symptoms and in matched controls.

2. Plasma levels of neurotensin, a newly discovered highly potent, hypotensive ileal peptide, were significantly increased in symptomatic patients compared with those of controls [20 min rise of 43 ± 6.0 (mean ± sem) pmol/l in 19 symptomatic patients, 8.0 ± 5.5 pmol/l in 20 postoperative symptom-free patients, and 4.1 ± 3.5 pmol/l in 20 pre-operative patients with duodenal ulcer, P < 0.01].

3. The rise in enteroglucagon was greater than normal but of similar magnitude to that seen in several other gastrointestinal conditions not associated with dumping symptoms.

4. The release of both gastric inhibitory peptide and motilin did not differ significantly from that of controls.
An Inactive, Prorenin-like Substance in Human Kidney and Plasma
Authors: Atlas S. A. , Laragh J. H. , Sealey Jean E. , Hesson T. E.
Published: August 2015

1. Plasma prorenin (inactive renin), which accounts for about 70% of the total renin in human plasma, was almost completely separated from active renin by affinity chromatography on Cibacron blue F3G-A-agarose. The slight residual renin activity present in the prorenin peak can be removed on concanavalin A-Sepharose, demonstrating that prorenin is completely inactive.

2. The renin activity of both human renal cortical extract and renal perfusate increased after incubation with trypsin. This trypsin-activable renin accounted for 15 and 40% of the total renin in extract and perfusate respectively.

3. Trypsin-activable renin from both renal extract and renal perfusate was, like plasma prorenin, almost completely separated from active renin on Cibacron blue F3G-A-agarose. After additional chromatographic steps, the trypsin-activable renin from renal cortical extract was found to be completely inactive.

4. We conclude that human kidney contains, and is able to release, a trypsin-activable renin that resembles plasma prorenin. It may differ from many of the 60 000 molecular-weight forms of renin previously identified in renal extracts, since these possess considerable intrinsic renin activity and probably represent a complex of renin with a binding protein.
Baroreflex Sensitivity Changes during the Development of Goldblatt Two-Kidney One-Clip Hypertension in Rats
Authors: Jones J. V. , Floras J. S.
Published: August 2015

1. The time course of changes in baroreceptor reflex sensitivity during the development of renovascular hypertension was studied in male Wistar rats in which the left renal arteries were constricted by silver wire clips of 0.18 mm internal diameter.

2. Groups of animals were studied at 3, 7, 14 and 25 days after induction of renovascular hypertension. Rats of comparable ages were included as controls. There was a significant decrease in mean baroreflex sensitivity from 0.950 ± 0.157 ms/mmHg (n = 8) in the normal control group to 0.537 ± 0.105 ms/mmHg (n = 8) in the 3 day hypertensive group (P < 0.05). Baroreflex sensitivity in the 3 day hypertensive rats was independent of the level of arterial pressure achieved in individual animals.

3. These changes in baroreflex sensitivity at 3 days precede the development of left ventricular hypertrophy and, as previously shown in this model, also precede structural vascular adaptation and resetting of the carotid sinus baroreceptor threshold.

4. A further loss of baroreflex sensitivity, which may be structurally based, occurred later. Baroreflex sensitivity in the 14 day hypertensive rats fell to 0.182 ± 0.039 ms/mmHg (n = 8) compared with the 3 day hypertensive rats (P < 0.01).
A Comparison of Multiple Forms of Renin in Rat Renal Perfusate with those in Renal Extract
Authors: Nakane Haruyuki , Nakane Yoko , Misumi Jiro , Saruta Takao , Corvol Pierre , Menard Joël
Published: August 2015

1. Physicochemical properties of renin secreted by isolated perfused rat kidney were examined and the results compared with those obtained for the renin in renal extract.

2. In renal extract, two high-molecular-weight reruns (molecular weight 65 000 and 55 000) and one low-molecular-weight renin (molecular weight 39 000) were found. Their relative proportion varied depending on extraction conditions. By acidification, high-molecular-weight renins were converted into low-molecular-weight renin without marked changes in activity.

3. In renal perfusate only low-molecular-weight renin was found after renin stimulation by isoprenaline or anoxia. Inactive renin was not found.

4. Renin in renal extract and perfusate samples were both found to consist of at least four isoenzymes having different isoelectric points (pI). The pI patterns were identical in renal extract and perfusate samples: pI 5.7 (60-70%), 5.5 (15-25%), 5.3 (5-10%) and 5.0-5.2 (2-5%).

5. These results indicate that the native renin secreted by rat kidney consists entirely of the low-molecular-weight and active form comprising multiple isoenzymes with a stable pI pattern.
Immunochemical Differences between Angiotensin I-Forming Enzymes in Man
Authors: Menard J. , Galen F.-X. , Devaux C. , Kopp N. , Auzan Colette , Corvol P.
Published: August 2015

1. Human plasma, amniotic fluid and acidified amniotic fluid were incubated at pH 5.5 with the same concentrations of human plasma renin substrate and rat plasma renin substrate. They produced three to eight times more angiotensin I with human than with rat renin substrate. By contrast, human brain extracts generated 20 times more angiotensin I when incubated with rat plasma renin substrate than with human plasma renin substrate.

2. Serial dilutions of anti-(human renin) antibody inhibited, in a dose-dependent manner, the production of angiotension I when plasma, amniotic fluid and brain extracts were incubated with human plasma renin substrate. They also inhibited the production of angiotensin I when plasma and amniotic fluid were incubated with rat plasma renin substrate. They were ineffective on the angiotensin I generation by human brain extracts acting on rat plasma renin substrate.

3. Affinity chromatography on an haemoglobin-Sepharose gel separated the fraction of brain extract acting on human renin substrate and inhibited by anti-(human renin) antiserum; this was not retained on the gel at pH 3.3. Part of the angiotensin I-forming activity detected by rat renin substrate hydrolysis was not retained on the gel and part was eluted at pH 8.5. These angiotensin I-forming activities did not hydrolyse human renin substrate, and were not neutralized by anti-(human renin) antibody.

4. These results demonstrate that a renin, immunochemically identical with renal, plasma and amniotic fluid renin, is present in the human brain. Other angiotensin I-forming activity, acting on an heterologous substrate at a more acidic pH, is also present in human brain.
Subcellular Fractionation Studies of Human Rectal Mucosa; Localization of the Mucosal Peptide Hormones
Authors: Dawson J. , Bryant M. G. , Bloom S. R. , Peters T. J.
Published: August 2015

1. Analytical subcellular fractionation techniques have been applied to endoscopic human rectal biopsies to study the localization of enteroglucagon, somatostatin, vasoactive intestinal peptide and the properties of the principal subcellular organelles.

2. The peptide hormones, detected by radioimmunoassay, showed particulate localizations with single peaks in the density gradients for enteroglucagon (modal density 1.25) and somatostatin (modal density 1.23). Vasoactive intestinal peptide showed a less discrete localization but demonstrated a major peak (modal density, 1.17) with a small subsidiary peak (modal density 1.24).

3. The following organelles, characterized by their marker enzymes, were located in the density gradients; plasma membrane (5′-nucleotidase), mitochondria (malate dehydrogenase), peroxisomes (catalase), lysosomes (β-N-acetyl-d-glucosaminidase), endoplasmic reticulum (neutral α-d-glucosidase) and cytosol (lactate dehydrogenase).

4. This technique can be used to investigate disease of the human rectum at a subcellular level.
Fat Metabolism in Heavy Exercise
Authors: Jones N. L. , Heigenhauser G. J. F. , Kuksis A. , Matsos C. G. , Sutton J. R. , Toews C. J.
Published: August 2015

1. To investigate differences between the metabolic effects of light and heavy exercise, five healthy males (mean maximal oxygen intake 3.92 litres/min) exercised for 40 min at 36% maximum power (light work) and 70% maximum power (heavy work) on separate days, after an overnight fast.

2. A steady state was achieved in both studies between 20 and 40 min in: oxygen intake (1.42 and 2.64 litres/min respectively); respiratory exchange ratio (0.89 and 1.01); plasma lactate concentration (1.78 and 9.94 mmol/l).

3. Plasma palmitate turnover rate (14C) was unchanged from resting values in light work but was decreased by 40% (from 104 ± 16 to 63 ± 8 μmol/min) in heavy work. Heavy work was associated with falls in the plasma concentrations of all free fatty acids measured: palmitic acid (C16:0), oleic acid (C18:1), stearic acid (C18:0), linoleic acid (C18:2) and palmitoleic acid (C16:1).

4. In contrast to the fall in palmitate turnover the increase in plasma glycerol was greater in heavy exercise (0.054–0.229 mmol/l) than in light exercise (0.053–0.094 mmol/l), suggesting that lipolysis was occurring which did not lead to influx of free fatty acids into plasma.

5. In light exercise fat metabolism may be controlled to favour adipose tissue lipolysis and extraction of free fatty acids by muscle from the circulation, whereas in heavy exercise adipose tissue lipolysis is inhibited and hydrolysis of muscle triglycerides may play a more important part.

6. The finding of a high respiratory exchange ratio may not exclude the use of fat as a major fuel source in exercise associated with lactate production.
Renin in Rat and Mouse Brain: Immunohistochemical Identification and Localization
Authors: Inagami T. , Celio M. R. , Clemens D. L. , Lau D. , Takii Y. , Kasselberg A. G. , Hirose S.
Published: August 2015

1. Localization of renin in rat and mouse brain was determined by immunohistochemical methods with specific anti-renin antibodies.

2. Renin-containing neuronal cells were found in the medulla oblongata, cerebellar nuclei and hypothalamus. Purkinje cells contained renin.

3. Glia-like cells contained renin. Some of them are closely associated with vascular walls and these vascular walls were renin positive.

4. The pineal gland, adenohypophysis and choroid plexus contained renin.

5. The extensive distribution of renin suggests functions other than those which have been associated with the hypothalamus.
Subcellular Localization of Serotonin and Motilin in the Human Jejunum
Authors: Dawson J. , Bryant M. G. , Cox A. G. , Christofides N. D. , Bloom S. R. , Peters T. J.
Published: August 2015

1. Analytical subcellular fractionation techniques have been applied to human jejunal homogenates to study the localization of serotonin and motilin.

2. Serotonin, detected by a fluorimetric assay, showed two distinct particulate distributions in the density gradients with modal densities of 1.14 and 1.20. Motilin, whether detected by N-terminal or C-terminal specific antibodies showed similar density distributions with a modal density of 1.20, coinciding with the denser peak of serotonin.

3. These results lend support to the histochemical suggestions that motilin is located in a serotonin-containing granule.
Immunocytochemical Localization of Angiotensin II and Vasopressin in Rat Hypothalamus: Evidence for Production in the Same Neuron
Authors: Kilcoyne M. M. , Hoffman D. L. , Zimmerman E. A.
Published: August 2015

1. By immunoperoxidase technique, immunoreactive angiotensin II (ANG II) was located in the cell bodies of many magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus and their pathways to median eminence and posterior pituitary gland in the rat.

2. Like vasopressin and its neurophysin, but not oxytocin, ANG II was also found in parvocellular neurons in the suprachiasmatic nucleus.

3. Analysis of these peptides in the same magnocellular neurons reveals that ANG II is localized primarily in vasopressin cells.

4. Like vasopressin and its precursor, ANG II is deficient in homozygous Brattleboro rats with diabetes insipidus.

5. In adrenalectomized rats increases in vasopressin and its neurophysin in median eminence are associated with increases in ANG II.

6. The data suggest that the ANG II demonstrated shares antigenic determinants with the vasopressin precursor, or is regulated in a similar way to vasopressin in the same neurons.
Hypotensive Effects of Captopril, Saralasin and Bromocriptine in Spontaneously Hypertensive Rats
Authors: Hutchinson J. S. , Doyle A. E.
Published: August 2015

1. Neurosecretion of peptides from superfused neurohypophyses in vitro was inhibited by dopamine.

2. This inhibition was dose-dependent.

3. Intravenous injection of the dopamine agonist, bromocriptine, lowered blood pressure in spontaneously hypertensive rats within 15 min.

4. Saralasin or captopril also lowered blood pressure of spontaneously hypertensive rats, but progressively over a period of 3 h.

5. The results suggest that dopamine and angiotensin have opposite effects on the neurosecretion of vasopressin.

6. Vasopressin appears to be involved in maintenance of blood pressure in the spontaneously hypertensive rat but is apparently not the only factor.
Dopaminergic Control of Aldosterone Secretion is Independent of the Renin—Angiotensin System in Rats
Authors: Sowers J. R. , Tuck M. L. , Barrett J. , Sambhi M. P. , Golub M. S.
Published: August 2015

1. In rats, intra-arterial metoclopramide, a dopamine antagonist, resulted in an elevation of plasma aldosterone at 5 min and plasma renin activity at 10 min and peak aldosterone and renin responses at 10 and 30 min respectively.

2. Pre-administration of l-dopa blunted and delayed aldosterone and renin responses to metoclopramide, indicating that metoclopramide-induced plasma aldosterone and plasma renin activity increments are mediated by a direct effect of blockade of dopamine receptors rather than other effects of this drug.

3. Pre-administration of angiotensin converting enzyme inhibitor, captopril (SQ 14 225) and the angiotensin II antagonist, saralasin, as well as bilateral nephrectomy did not significantly affect the aldosterone response to metoclopramide, Thus dopaminergic modulation of aldosterone secretion occurs independently of alterations in the renin-angiotensin system.

4. Modulating effects of dopamine on plasma aldosterone are probably mediated by direct effects as well as by interaction with other factors influencing aldosterone secretion at the adrenal zona glomerulosa.
Influence of Sodium on Experimental Renovascular Hypertension in Rats
Authors: Taquini C. M. , Gallo A. , Basso N. , Taquini A. C.
Published: August 2015

1. Rats on normal sodium diet (group 1) and on chronically maintained low sodium diet (group 2) were studied during a control period, after clipping the renal artery (two-kidney, one-clip hypertension) and after nephrectomy (one-kidney, one-clip hypertension).

2. The low sodium diet neither prevented the development nor changed the severity of two-kidney, one-clip hypertension, and the latter was not accompanied by an increase in plasma renin activity.

3. After nephrectomy arterial pressure further increased and plasma renin activity decreased in group 1, and both remained unchanged in group 2.

4. Blood volume was the same in both groups 10 days before and 10 days after nephrectomy.

5. Sodium does not seem to be ‘necessary’ in the two-kidney, one-clip hypertension although it may play an enhancing role in the one-kidney model.
An Inherited Sodium Ion-Potassium Ion Cotransport Defect in Essential Hypertension
Authors: Garay R. P. , Dagher G. , Meyer P.
Published: August 2015

1. In erythrocytes, the extrusion of a cell sodium load is accomplished by the ouabain-sensitive sodium-potassium pump and by the frusemide-sensitive sodium-potassium cotransport, which operate against the passive sodium permeability. All these three components of the cell sodium balance were studied in essential hypertension (410 subjects were investigated).

2. An abnormally low rate of net sodium extrusion by the sodium-potassium cotransport system was observed in essential hypertensive patients and in a high proportion of their young normotensive offspring. A normal cotransport system found in secondary hypertensive subjects devoid of familial history of hypertension confirmed that the abnormal cotransport system is not the consequence of high blood pressure per se.

3. A 20–40% increase in the rate of net sodium extrusion by the sodium-potassium pump seems to compensate for the abnormal cotransport in erythrocytes from some young normotensive subjects born of essential hypertensive parents and from some benign essential hypertensive subjects.

4. No difference could be detected between the passive sodium permeability of erythrocytes from hypertensive subjects and in those from normotensive controls.

5. In conclusion, essential hypertension seems to be associated with an inherited defect in the sodium-potassium cotransport system. We propose therefore the laboratory study of this system for: (i) the distinction between essential and secondary hypertension and (ii) the preventive investigation of young normotensive subjects in hypertensive families.
Calcium Accumulation and Calcium Binding by the Cell Membranes of Cardiomyocytes and Smooth Muscle of Aorta in Spontaneously Hypertensive Rats
Authors: Orlov S. N. , Postnov Yu. V.
Published: August 2015

1. The ability of isolated membrane fractions of cardiomyocytes, aortic smooth muscle and erythrocytes from spontaneously hypertensive rats to bind calcium was investigated isotopically.

2. Plasma membranes of aortic smooth muscle and erythrocytes of spontaneously hypertensive rats possess a lower calcium-binding ability than preparations from normotensive controls.

3. Sarcoplasmic reticulum from the myocardium of spontaneously hypertensive rats had a lower ability to accumulate calcium.

4. Changes in the calcium-binding ability of the erythrocyte membrane of spontaneously hypertensive rats was related to the diminution of the amount of exchangeable calcium on the inner part of the membrane. The latter may be the cause of the increase of erythrocyte membrane permeability for sodium in spontaneously hypertensive rats and in patients with essential hypertension.
Increased Adrenaline, β-Adrenoreceptor Stimulation and Phospholipid Methylation in Pineal Gland of Spontaneously Hypertensive Rats
Authors: Saavedra J. M.
Published: August 2015

1. In pineal glands of adult spontaneously hypertensive rats (Okamoto strain), dopamine levels increased 34%, adrenaline concentrations increased 152% and noradrenaline levels decreased by 26%, when compared with Wistar-Kyoto normotensive controls.

2. These results are consistent with the hypothesis of an increased uptake of peripheral adrenaline resulting in increased release of noradrenaline from pineal sympathetic nerves in hypertensive rats.

3. The activity of pineal N-acetyltransferase was increased fourfold in hypertensive rats, indicating increased stimulation of pineal β-adrenoreceptors.

4. Methylation of pineal membrane phospholipids was also increased (100-320%) in hypertensive rats.

5. These results indicate a correlation in vivo between increased β-adrenoreceptor stimulation and increased methylation of membrane phospholipids in the rat pineal gland, which could result in changes in membrane fluidity and affect the coupling of the β-adrenoreceptors to the adenylate cyclase.
Early Changes in Noradrenaline Content of Some Brain Nuclei in Spontaneously Hypertensive Rats
Authors: Le Quan-Bui Kim Hanh , Elghozi Jean-Luc , Devynck Marie-Aude , Meyer Philippe
Published: August 2015

1. The noradrenaline content of individual brain nuclei was measured by using high-pressure liquid chromatography coupled with electrochemical detection.

2. This study was performed on spontaneously hypertensive rats during the development of hypertension (4 and 12 weeks) and also on deoxycorticosterone-salt hypertensive rats after 1 and 4 weeks of treatment.

3. In young spontaneously hypertensive rats a significant decrease in noradrenaline content was observed in some medullary and hypothalamic nuclei which are involved in cardiovascular regulation. No change was observed after deoxycorticosterone-salt treatment.

4. It is proposed that a change in adrenergic activity, restricted to brain cardiovascular centres, could represent a mechanism triggering spontaneous hypertension.
The Role of Endogenous Opiates in the Area Postrema Pressor Pathway
Authors: Szilagyi Julianna E. , Ferrario C. M.
Published: August 2015

1. Intra-vertebral artery-administered angiotensin II acts at the area postrema to facilitate central sympathetic vasomotor activity. Recent evidence suggests a possible role of the opiate system in the mechanism of action of angiotensin II at the level of the brain stem.

2. In these experiments, we show that the morphine antagonist naloxone reduces significantly the magnitude of the pressor response to vertebral artery-infused angiotensin II.

3. Morphine, in contrast, doubled the peak of the vertebral response to identical doses of the peptide. Neither naloxone nor morphine affected the pressor responses to intravenously administered angiotensin II.

4. The data suggest that the endogenous opiate system in the medulla modulates the cardiovascular effects of angiotensin II at the level of the area postrema.
Central and Regional Normetadrenaline in Evaluation of Neurogenic Aspects of Hypertension: Aid to Diagnosis of Phaeochromocytoma
Authors: Dequattro V. , Sullivan P. , Foti A. , Bornheimer J. , Schoentgen Sarah , Versales Gilda , Levine D. , Kobayashi K.
Published: August 2015

1. Free normetadrenaline concentrations in plasma of patients with phaeochromocytoma were elevated 20–1000-fold as compared with values in primary hypertensive subjects.

2. Spinal fluid normetadrenaline was 1.8-16% of the simultaneous plasma values in patients with phaeochromocytoma, whereas levels in spinal fluid exceeded those of plasma in primary hypertension.

3. Spinal fluid noradrenaline was 7.9-58% of simultaneous values of plasma noradrenaline in patients with phaeochromocytoma, whereas values in plasma and cerebrospinal fluid were similar in primary hypertension.

4. Plasma noradrenaline and normetadrenaline levels were both elevated in veins from regions subsequently found to harbour chromaffin tumours.

5. The excessive amounts of normetadrenaline produced in phaeochromocytoma enters plasma but not spinal fluid and can be used for diagnosis and localization of phaeochromocytoma.
Increased Sympathetic Activity and Blood Pressure in Young Asymptomatic Men with ‘Organic’ T-Wave Aberrations in the Electrocardiogram
Authors: Atterhog J.-H. , Eliasson K. , Hjemdahl P.
Published: August 2015

1. Twelve asymptomatic young men with ‘primary’ T-wave aberrations in the electrocardiogram (group T) and 13 matched controls were subjected to a mental stress test, isometric exercise and a cold pressor test.

2. Plasma catecholamines and haemodynamics were studied.

3. Group T had signs of increased sympathetic activity at rest and enhanced sympatho-adrenal reactivity during stress.

4. Systolic blood pressure was consistently elevated in group T.

5. The T-wave aberrations may be explained by the increased sympathetic activity.

6. Several similarities exist between group T and borderline hypertensive subjects.
Is Substance P the Transmitter at the First Synapse of the Baroreceptor Reflex in Rats and Cats?
Authors: Haeusler G. , Osterwalder R.
Published: August 2015

1. Substance P, injected into a lateral brain ventricle of urethane-anaesthetized rats, caused dose-dependent increases in blood pressure and heart rate.

2. By contrast, exposure of the obex region of the medulla oblongata to pieces of filter paper soaked in substance P-containing solution resulted in falls of blood pressure and heart rate in both rats and cats.

3. A more precise application of substance P to the first synapse of the baroreceptor reflex by micro-injection into defined areas of the nucleus of the solitary tract also led to an activation of the baroreceptor reflex.

4. Capsaicin, which is known to release substance P from primary afferents, mimicked the sympatho-inhibitory and cardiovascular effects of substance P when applied locally to the nucleus of the solitary tract.

5. The results are compatible with a transmitter or neuromodulatory role for substance P at the first synapse of the baroreceptor reflex.
Reno-Renal and Reno-Adrenal Reflexes in the Rat
Authors: Recordati G. , Genovesi S. , Cerati D. , Di Cintio R.
Published: August 2015

1. Experiments were carried out to investigate whether the activation of renal chemoceptive receptors by natural stimuli might induce reflex alterations of efferent postganglionic activity to the ipsilateral kidney and preganglionic activity to the ipsilateral adrenal.

2. In anaesthetized rats with intact nervous system back-flow of urine and occlusion of the renal artery were accompanied by increments in efferent sympathetic activity both to the kidney and adrenal without concomitant changes in heart rate and blood pressure.

3. Greater excitatory responses in nerve activity to the same test stimuli were observed in rats with the spinal cord cut at C1.

4. These results indicate that the natural activation of renal chemoceptive receptors might induce reno-renal and reno-adrenal excitatory reflexes which are likely to be integrated at spinal and supraspinal levels.
Regional Blood Flows in High-Cardiac-Output Hypertension
Authors: Liard J. F.
Published: August 2015

1. Mean arterial pressure, cardiac output (electromagnetic flow-meter) and regional blood flows (15 μm radioactive microspheres) were measured repeatedly in eight dogs receiving a salt and water load after renal mass reduction as well as in six control animals.

2. As previously observed, hypertension developed in the salt-loaded dogs with an initial increase in cardiac output followed by a secondary rise in total peripheral resistance.

3. Much of the early increase in cardiac output was distributed to the skeletal muscle vascular bed.

4. Total peripheral resistance changes did not reflect the resistance of individual vascular beds in the early stages of salt and water load hypertension; indeed, resistance in the muscle vascular bed was decreased and that in the splanchnic area and the bone increased on the first day of salt and water load when total peripheral resistance was unchanged.
Alterations in Cardiac Function and Cardiopulmonary Blood Volume in Chronic Sodium Depletion in Dogs
Authors: Lynn M. P. , Fouad F. , Cook S. A. , Napoli Carmen A. , Ferrario C. M.
Published: August 2015

1. Chronic sodium depletion in dogs is associated with a blunting of the pressor response to carotid occlusion. After section of the vagus nerves this pressor response reverts to normal although atropine is without effect, suggesting a possible role for increased activity of cardiopulmonary vagal afferents in suppressing sympathetic outflow. Since increases in central blood volume stimulate vagal afferents, cardiopulmonary haemodynamics were studied by radioisotope dilution before and after 3 and 4 weeks of dietary sodium restriction together with frusemide.

2. Sodium depletion was associated with significant decreases in cardiac output, ejection fraction and total blood volume; the cardiopulmonary blood volume increased but the change was not statistically significant (P<0.2). These changes were accompanied by a significant increase in the ratio cardiopulmonary blood volume/total blood volume and a decrease in the ratio cardiac output/cardiopulmonary blood volume.

3. Results indicate that sodium depletion may be accompanied by a paradoxical translocation of blood to the cardiopulmonary region in part due to depressed ventricular performance.
Total Body Potassium Falls with Age
Authors: Rajagopalan B. , Thomas G. W. , Beilin L. J. , Ledingham J. G. G.
Published: August 2015

1. Plasma volume, 24 h urine sodium and total body potassium were similar among 89 previously untreated patients with mild hypertension and 89 control subjects matched for age and sex.

2. Total body potassium correlated with renin activity in both hypertensive patients and controls.

3. Renin activity and total body potassium fell significantly with age in both groups.

4. The relationship between renin and total body potassium was no longer present when the effects of age were allowed for in a partial correlation.
β-Adrenoreceptor-Blocking Agents and the Blood-Brain Barrier
Authors: Cruickshank J. M. , Neil-Dwyer G. , Cameron M. M. , McAinsh J.
Published: August 2015

1. Sixteen neurosurgical patients received (oral) β-adrenoreceptor-blocking agents (β-receptor blockers) for 3–22 days.

2. Lipophilic β-receptor blockers (propranolol) and metoprolol appeared in cerebrospinal fluid at concentrations similar to the free drug plasma concentration.

3. Cerebrospinal fluid concentrations of β-receptor blockers were poor predictors of brain concentrations

4. Both lipophilic β-receptor blockers appeared in high concentrations in the brain: the brain/plasma ratio was approximately 15:1.

5. Hydrophilic atenolol appeared at low concentrations in brain tissue (about 20 times lower than the lipophilic β-receptor blockers): the brain/plasma ratio was approximately 0.1:1.

6. Central nervous system-related side effects associated mainly with lipophilic β-receptor blockers possibly result from high brain tissue concentrations.
α- and β-Adrenoreceptor-Mediated Control of Brain Noradrenaline Neurons and Antihypertensive Therapy
Authors: Svensson T. H. , Almgren O. , Dahlof C. , Elam M. , Engberg G. , Hallberg H. , Thoren P.
Published: August 2015

1. The central noradrenergic nucleus locus coeruleus seems to participate in arousal reactions and cardiovascular modulation. Using single cell recording techniques and biochemical assays, we have studied locus coeruleus neuronal regulation and its interaction with antihypertensive treatments.

2. Acute (5 μg/kg intravenously) or chronic clonidine treatment (2 μg/ml in drinking water for 2 weeks) significantly reduced locus coeruleus neuronal activity, probably via activation of α2-receptors within the nucleus. Termination of the chronic regimen increased the noradrenaline cell firing rates above baseline, a finding possibly related to the withdrawal syndrome.

3. In spontaneously hypertensive rats the activation of locus coeruleus neurons by yohimbine, an α2-receptor antagonist, was increased compared with that in normotensive (Wistar-Kyoto) control rats, implying an altered α2-receptor-mediated control of the central noradrenaline neurons.

4. Chronic treatment with dl-propranolol (5 or 10 mg/kg daily for 1 week) but not d-propranolol or acutely given dl-propranolol significantly reduced neuronal activity in the locus coeruleus, an effect which may relate to mental and cardiovascular actions of β-receptor-blocking drugs.

5. In contrast, chronically given salbutamol, a β2-receptor agonist (5 mg/kg subcutaneously for 2 weeks), increased brain noradrenaline utilization. Thus β-receptors probably participate in the control of brain noradrenaline neurons.
Influence of Breath Holding at Total Lung Capacity on Maximal Expiratory Flow Measurements
Authors: Higenbottam T. , Clark T. J. H.
Published: August 2015

1. Forced exhalations performed from volumes below total lung capacity, so-called partial expiratory flow-volume curves, are suggested to be more sensitive in detecting airways bronchoconstriction than maximal expiratory flow-volume curves begun at total lung capacity.

2. In eight healthy men both maximal and partial expiratory flow-volume curves were measured where breath was held at total lung capacity or 70% of vital capacity respectively, for either 0 or 15 s before performing the forced exhalation. An histamine aerosol was used to provoke bronchoconstriction.

3. The results showed that the 15 s breath hold caused greater reduction in expiratory flow rates after histamine for both maximal and partial expiratory flow-volume curves than either manoeuvres performed with no breath hold.

4. A breath hold of 15 s at total lung capacity appeared to make the maximal expiratory flow-volume curve as sensitive as a partial expiratory flow-volume curve in detecting the response to histamine as well as providing measurements of forced expiratory volume in 1 s and vital capacity. Forced spirometry after a 15 s breath hold at total lung capacity therefore provides an easy and sensitive technique for detecting bronchoconstriction.
Renin in the Mouse Kidney Has a Molecular Weight of 40 000
Authors: Poulsen K. , Nielsen A. H.
Published: August 2015

1. Mouse kidney was homogenized in a mixture of serine-metallo- and thiol-enzyme inhibitors. The homogenate proteins were separated with respect to size and charge by gel filtration, agarose electrophoresis and polyacrylamide-gel electrophoresis.

2. Renin was localized by its enzymatic activity by using the antibody trapping radioimmunoassay for angiotensin I, before and after acid treatment and limited proteolysis. Renin was also localized by its antigenic properties by using antirenin antibodies elicited against pure mouse submaxillary renin. The antibody cross-reacted fully with mouse kidney renin and with high-molecular-weight renin forms in mouse plasma.

3. In the kidney only fully enzymically active 40 000 renin could be detected enzymically and antigenically. No high-molecular-weight renin or inactive renin was demonstrable.

4. Two electrophoretically different renin forms were seen in accordance with renin being a glycoprotein. They were both fully enzymically active with identical specific enzymatic activities.

5. The mouse kidney renin had a specific enzymatic activity identical with that of pure mouse submaxillary renin, being 0.4 Goldblatt unit/μg.
Effect of a Long-Term Fat-Modified Diet on Serum Lipoprotein Levels of Cholesterol and Triglyceride in Patients on Home Haemodialysis
Authors: Wass V. J. , Jarrett R. J. , Meilton V. , Start M. K. , Mattock M. , Ogg C. S. , Cameron J. S.
Published: August 2015

1. Changes in serum total and lipoprotein fraction triglyceride and cholesterol levels were studied in 24 adults on home haemodialysis. Half the patients were randomly allocated to a low cholesterol (mean 200 mg/day), fat-modified diet (mean polyunsaturated/saturated fat ratio of 1.0 with a mean of 43% of the total energy content derived from fat).

2. Before dietary manipulation, triglyceride levels in all lipoprotein fractions were significantly higher (P < 0.02) than in a control group of age and sex matched normal subjects. Total cholesterol, very-low-density-lipoprotein (VLDL) and low-density-lipoprotein (LDL) cholesterol were also significantly raised (P < 0.02), but high-density-lipoprotein (HDL) cholesterol was normal. In the patients on a fat-modified diet triglyceride levels did not alter in any of the lipoprotein fractions. Total cholesterol and LDL cholesterol levels fell significantly into the normal range (P < 0.002 and < 0.001 respectively) but VLDL and HDL cholesterol levels did not change.

3. Hypertriglyceridaemia is the most common lipid abnormality in patients with renal failure and a long-term fat-modified diet is, therefore, of limited therapeutic importance in these patients unless there is a low HDL/LDL cholesterol ratio.
Effect of Hydrochlorothiazide on 1,25-dihydroxyvitamin D3-induced Changes in Calcium Metabolism in Experimental Hypoparathyroidism in Rats
Authors: Rizzoli R. , Hugi K. , Fleisch H. , Bonjour J.-P.
Published: August 2015

1. Chronic administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can normalize plasma calcium in human hypoparathyroidism and in thyroparathyroidectomized animals. The effect of 1,25(OH)2D3 on plasma calcium is associated with an increase in urinary calcium excretion. In an attempt to prevent this increase, thyroparathyroidectomized rats receiving 1,25(OH)2D3 were also treated with hydrochlorothiazide for 9–11 days.

2. Calcium clearance studies show that hydrochlorothiazide stimulated the tubular reabsorption of calcium in thyroparathyroidectomized rats treated with 1,25(OH)2D3.

3. Calcium balance and kinetic studies indicated that hydrochlorothiazide decreased 1,25(OH)2D3-induced hypercalciuria in thyroparathyroidectomized rats. Hydrochlorothiazide did not affect the 1,25(OH)2D3-induced increase in plasma calcium. The hypocalciuric effect of hydrochlorothiazide was not associated with significant changes in calcium deposition into or release from bone.

4. In thyroparathyroidectomized rats treated with 1,25(OH)2D3 the hypocalciuric effect of hydrochlorothiazide was associated with a fall in intestinal calcium absorption. Overall, the calcium balance was unaffected.

5. Thus it appears that hydrochlorothiazide reduces the 1,25(OH)2D3-induced hypercalciuria in parathyroid hormone-deficient animals by decreasing intestinal calcium absorption.

Despite the decreased absorption, hydrochlorothiazide does not reduce the 1,25(OH)2D3-induced increase in plasma calcium.
Local Regulation of Blood Flow in Subcutaneous Tissue in Patients with Acute Myocardial Infarction
Authors: Skagen K. , Henriksen O. , Amtorp O. , Fog-Møller F. , Lam H.
Published: August 2015

1. Local regulation of subcutaneous blood flow in the forearm was studied in the acute phase of myocardial infarction. Blood flow was measured by the local 133Xe-washout technique.

2. Plasma concentrations of noradrenaline and adrenaline were increased on day 1, suggesting an increase in sympathetic neuronal activity, but gradually returned to normal thereafter.

3. Subcutaneous blood flow on day 1 was far below normal (38%) and steadily increased to reach normal at day 7 after coronary occlusion. The sympathetic vasoconstrictor activity that caused the initial reduction in flow could be blocked by proximal nervous blockade, increasing the subcutaneous blood flow by 130, 63 and 14% on days 1, 3 and 7 respectively after coronary occlusion. A normal response to decrease in arterial perfusion pressure was observed, suggesting that intrinsic vascular reactions responsible for autoregulation of blood flow were not affected by the increase in sympathetic vasoconstrictor activity. The vasoconstrictor response to increase in venous transmural pressure could not be demonstrated on day 1 after coronary occlusion but gradually reappeared during the following days.

4. Abolition of the vasoconstrictor response is most likely to be due to a centrally elicited increase in sympathetic activity, as a normal vasoconstrictor response was obtained after proximal nervous blockade. Thus the local sympathetic reflex mechanism underlying the vasoconstrictor response appears to be suppressed by a centrally elicited increase in sympathetic discharge rate.
Tubular Handling of Phosphate along the Nephron of Thyroparathyroidectomized Rats Injected with Ethane-1-Hydroxy-1,1-Diphosphonate
Authors: Mühlbauer R. C. , Bonjour J.-P. , Fleisch H.
Published: August 2015

1. Previous studies have shown that in thyroparathyroidectomized rats injection of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at doses that inhibit bone mineral retention (0.16 mmol = 10 mg of phosphorus/kg body wt. per day subcutaneously) leads to a decrease in the net tubular reabsorption of phosphate.

2. In the present work the tubular response to EHDP (0.16 mmol/kg body wt.) injected subcutaneously for 9 days has been localized by free-flow micropuncture in thyroparathyroidectomized rats.

3. The results show that the net tubular reabsorption of phosphate along the first portion of the (early) proximal tubule was markedly depressed in the EHDP-injected thyroparathyroidectomized rats compared with that in the pair-fed thyroparathyroidectomized control animals. In this latter group the delivery of phosphate to the distal tubule was larger than in the final urine, confirming previous reports. In the EHDP-injected thyroparathyroidectomized rats no difference in delivery of phosphate was found between the distal tubule and the final urine, suggesting that diphosphonate inhibited net reabsorption of phosphate in the terminal nephron.

4. The sites of the EHDP-induced changes in the tubular handling of phosphate were similar to those previously determined for the adaptive response to an increase in the supply of phosphate.
Effect of Head-Up Tilt on Subcutaneous Blood Flow during the Course of Acute Myocardial Infarction
Authors: Skagen K.
Published: August 2015

1. Central and local regulation of subcutaneous blood flow in the forearm was studied in the acute phase of myocardial infarction.

2. Blood flow was measured by the local 133Xe-washout technique.

3. The vasoconstrictor response to increase in venous transmural pressure was not present on day 1 after coronary occlusion but gradually recurred during days 2, 3 and 7.

4. Passive 30° head-up tilt induced a vasoconstriction in subcutaneous tissue. There was no difference in this response at any time during the course of acute myocardial infarction. The vasoconstriction could be blocked by proximal nervous blockade.

5. Thus a decrease in baroreceptor activity induced by head-up tilt enabled a marked neurogenically mediated vasoconstriction in subcutaneous tissue, indicating that orthodromic impulse activity in sympathetic fibres can be further increased even on day 1 of acute myocardial infarction.