bluuebunny/crossref_metadata_2025 huggingface dataset:
Dexamethasone, Aldosterone and Kallikrein Release by Isolated Rat Kidney
Authors: Vio C. P. , Roblero J. S. , Croxatto H. R.
Published: August 2015

1. The effect of d-aldosterone and dexamethasone on kallikrein release was studied in the isolated rat kidney perfused with modified Krebs-Henseleit buffer.

2. Animals received d-aldosterone or dexamethasone (10 μg/100 g body weight) daily for 3 days. Their isolated kidneys were then perfused with the same steroids at rates of 2.0–2.5 μg/min for 30 min.

3. Dexamethasone increased kallikrein release significantly (P < 0.001) both in urine and in venous outflow.

4. d-Aldosterone had no significant effect on kallikrein release, either in urine or in venous outflow.
Increased Hepatic Fibrogenesis in the Cholesterol-Fed Mouse
Authors: Lee S. P.
Published: August 2015

1. Mice when fed a cholesterol/choline-supplemented diet for 4 weeks developed histologically fatty livers. This lipid overloading was associated with an increase in hepatic concentration of connective tissues.

2. Both histological and biochemical abnormalities regressed on stopping the cholesterol diet for another 4 weeks. With continuing feeding for 24 weeks these abnormalities were sustained.

3. In the absence of available evidence that cholesterol is ‘toxic’ to the liver, it is concluded that lipid loading alone increases hepatic fibrogenesis.
Effect on Blood Lipids and Haemostasis of a Supplement of Cod-Liver Oil, Rich in Eicosapentaenoic and Docosahexaenoic Acids, in Healthy Young Men
Authors: Sanders T. A. B. , Vickers Marguerite , Haines A. P.
Published: August 2015

1. Twelve healthy male subjects took a daily supplement of 20 ml of cod-liver oil for 6 weeks. This provided 1.8 g of eicosapentaenoic acid (20:5ω3) and 2.2 g of docosahexaenoic acid (22:6ω3). The effects of the supplement on blood lipids, haemostatic variables, bleeding time and plasma vitamin A and carotene were studied. In seven subjects platelet aggregation induced by adenosine 5′-pyrophosphate (ADP) was also studied.

2. The proportions of 20:5ω3 and 22: 6ω3 in platelet and erythrocyte phosphoglycerides were substantially increased by the supplement mainly at the expense of ω6 polyunsaturated fatty acids.

3. Mean plasma triglyceride concentrations were reduced and those of high-density-lipoprotein (HDL) cholesterol were increased by the supplement.

4. The mean bleeding time was significantly prolonged after 3 weeks of taking the supplement, but had returned to the presupplementation value 5 weeks after withdrawal of the supplement.

5. The maximum estimated response to platelet aggregation induced by ADP was increased by the supplement.

6. The mean levels of antithrombin III (immunological) and blood pressure were lower at the end of the period of supplementation and remained so 5 weeks after withdrawal of the supplement. No significant changes in other variables were noted.
Cardiovascular Effects of Vasopressin Infused into the Vertebral Circulation of Conscious Dogs
Authors: Liard J. F. , Dériaz O. , Tschopp M. , Schoun J.
Published: August 2015

1. Seven conscious dogs received arginine-vasopressin infusions (100 and 1000 fmol min−1 kg−1) through catheters implanted in the left vertebral artery or the inferior vena cava while arterial pressure, cardiac output (electromagnetic flowmeter) and heart rate were measured.

2. Despite similar increases in plasma vasopressin concentrations, intravertebral administration induced a lesser increase in mean arterial pressure and a greater decrease in heart rate than the same infusion given intravenously.

3. These results suggest that vasopressin has an effect on structures of the central nervous system involved in cardiovascular control, possibly by affecting the baroreceptor reflex.
Characterization of Aggression-Provoked Renin from An Unknown Source in Male Mice
Authors: Poulsen K. , Pedersen E. B.
Published: August 2015

1. In male mice without kidneys and submaxillary, as well as sublingual, glands aggressive behaviour causes a vast release of renin [J. Bing & K. Poulsen (1979) Acta Physiologica Scandinavica, 107, 251–256].

2. This resulted in about an 800-fold increase in plasma renin concentration from the control level of 0.52 (range 0.15-0.8) Goldblatt unit (G.U.) × 10−3/ml to 430 (range 300–500) G.U. × 10−3/ml after aggression.

3. The aggression-provoked renin fulfil all the criteria so far studied for being active renin, identical with normal mouse plasma renin and pure submaxillary mouse renin.

4. It generates angiotensin I with renin substrate and Km (1.2 μmol/l) is the same. It is neutralized by pepstatin but not by inhibitors of metallo-, thiol and serine proteinases, indicating that it is an aspartate proteinase (acidic proteinase).

5. It is a 40 000-mol.wt. renin, which has full enzymatic activity with a specific enzymatic activity of 0.32 G.U./μg, identical with that of normal plasma renin.

6. Its enzymatic activity is neutralized by a specific antibody against pure submaxillary renin. It is measurable in the direct renin radioimmunoassay with a dilution curve which parallels that of the standards. It demonstrates complete antigenic identity with pure submaxillary renin in crossed immunoelectrophoresis.

7. Its origin is unknown.
A Non-Invasive γ-Camera Technique for the Measurement of Intrarenal Flow Distribution in Man
Authors: Gruenewald S. M. , Nimmon C. C. , Nawaz M. K. , Britton K. E.
Published: August 2015

1. A new method, based on the transit time of o-iodohippurate sodium (Hippuran) through the kidney, is proposed as an accurate non-invasive means of measuring the intrarenal flow distribution in man.

2. Data from [123I]Hippuran γ-camera renography are utilized in this method which employs region of interest selection, deconvolution, cross-correlation and curve subtraction to obtain the spectrum of transit times through the cortical and juxtamedullary nephrons.

3. In 12 normal subjects the mean percentage cortical flow was 83.9% (sem 0.7%) which is approximately the anatomical proportion of cortical nephrons in the human kidney.

4. Cortical flow as a percentage of total was significantly reduced in 21 hypertensive patients, all of whom had no evidence of primary renal disease (mean 74.6%, sem 1.5%).

5. In both the normotensive and hypertensive groups there was a good correlation between the results obtained from the left and right kidneys of the same patient showing the parallel physiological response of the two kidneys (mean difference 4%, P < 0.001).

6. Reduction in the distribution of flow to the cortical nephrons in the essential hypertensive patients supports the hypothesis that renal autoregulation is important in this syndrome.
Urine Free Dopamine in Normal Primigravid Pregnancy and Women Taking Oral Contraceptives
Authors: Perkins C. M. , Hancock K. W. , Cope G. F. , Lee M. R.
Published: August 2015

1. Urine free dopamine was estimated at predetermined points of the menstrual cycle in normal volunteer subjects and in women taking a combined oral contraceptive.

2. There was no alteration in 24 h urine dopamine during the normal menstrual cycle but, in contrast, combined oral contraceptives produced a fall which recovered premenstrually.

3. In 19 primigravid subjects 24 h urine free dopamine was estimated at monthly intervals throughout pregnancy and at the time of the postnatal examination.

4. Urine dopamine was elevated throughout pregnancy when compared with postnatal values. Women receiving an oral progestogen contraceptive at the time of the postnatal examination showed a further fall in urine dopamine.
Methods to Assess Breathlessness in Healthy Subjects: A Critical Evaluation and Application to Analyse the Acute Effects of Diazepam and Promethazine on Breathlessness Induced by Exercise or by Exposure to Raised Levels of Carbon Dioxide
Authors: Stark R. D. , Gambles S. A. , Lewis J. A.
Published: August 2015

1. Methods were devised and evaluated for inducing breathlessness by submaximal graded exercise in healthy subjects while objective measurements of cardiorespiratory function were made. Breathlessness was assessed with serial visual analogue scales (VAS), but with various measures to enhance repeatability.

2. A high level of reproducibility was obtained in spite of the subjective nature of the assessment. Individual responses were described by the relationship between breathlessness and ventilation. The sensitivity of the method was demonstrated by the use of inspiratory resistances which disturbed this relationship and caused greater breathlessness for a given level of ventilation.

3. These methods were applied to six healthy subjects to analyse the effects of acute doses of diazepam and promethazine on breathlessness induced by graded exercise or by rebreathing carbon dioxide in a double-blind study.

4. During exercise, diazepam and promethazine did not reduce breathlessness, although there was a minor trend with promethazine. During exposure to elevated levels of carbon dioxide, diazepam and promethazine had no effect on breathlessness. Diazepam and promethazine produced similar levels of sedation, but neither drug had significant effects on the ventilatory response to carbon dioxide. These preliminary findings contrast with those reported for chronic diazepam in ‘pink puffers’.

5. Raised levels of carbon dioxide caused greater breathlessness in relation to ventilation than did exercise.
Direct Measurement of the Hepatointestinal Extraction of Zinc in Cirrhosis and Hepatitis
Authors: Keeling P. W. N. , Ruse W. , Bull J. , Hannigan B. , Thompson R. P. H.
Published: August 2015

1. 65Zn was injected intravenously during transjugular liver biopsy and, from simultaneous hepatic and peripheral venous blood samples, hepatointestinal 65Zn extraction was calculated. Hepatic zinc content was measured in biopsy specimens.

2. On the same occasion samples of liver tissue were taken and their zinc content was measured by atomic absorption spectrophotometry.

3. Seven patients with cirrhosis had significantly lower hepatic zinc content and hepatointestinal zinc extraction than six control patients with mild liver disease. Six patients with chronic hepatitis had a mean hepatointestinal zinc extraction higher than control patients, whereas their mean hepatic zinc content was lower, although the former difference did not achieve statistical significance.

4. These results demonstrate that hepatointestinal extraction of zinc is impaired in cirrhosis, but not in chronic hepatitis.
Abnormal Calcium Handling by Isolated Cardiac Plasma Membrane from Spontaneously Hypertensive Rats
Authors: Pernollet Marie-Gabrielle , Devynck Marie-Aude , Meyer P.
Published: August 2015

1. Calcium handling by heart sarcolemmal vesicles from young spontaneously hypertensive rats (SHR) and normotensive Wistar—Kyoto (WKY) control rats were compared.

2. Calcium binding was significantly altered in SHR membranes at the physiological cytosolic Ca2+ concentrations which occur in resting and excited cells.

3. ATP-dependent calcium accumulation occurred at a higher rate in SHR than in WKY rat membrane vesicles.

4. Na+-dependent calcium extrusion of loaded vesicles was higher in SHR than in WKY rat membrane vesicles.

5. These alterations may play a significant role in the pathogenesis of hypertension.
Urinary Crystal Growth: Effect of Inhibitor Mixtures
Authors: Werness P. G. , Bergert Jan H. , Lee Karen E.
Published: August 2015

1. The crystal growth inhibitory activity of mixtures of known inhibitors and of mixtures of known inhibitors with normal urine was determined in calcium oxalate monohydrate and hydroxyapatite seeded crystal growth systems.

2. The inhibitory activity of the mixtures was compared with the measured activity of the individual components of the mixtures. All mixtures had inhibitory activity equal to the sum of the activities of their components, with the exception of RNA/urine mixtures in the calcium oxalate monohydrate system.

3. RNA/urine mixtures had inhibitory activity toward calcium oxalate monohydrate crystal growth which was less than would be predicted from the activity of the RNA and of the urine which were added. This reduced inhibitory activity was shown to be due probably to hydrolysis of RNA by the ribonuclease activity normally present in urine.

4. The results of these experiments make it possible to determine quantitatively the contribution of various naturally occurring urinary crystal growth inhibitors to the total measured inhibition observed in urine.
Paraventricular—Suprachiasmatic Lesions Prevent Salt-Induced Hypertension in Dahl Rats
Authors: Azar Silvia , Ernsberger P. , Livingston Suzanne , Azar P. , Iwai J.
Published: August 2015

1. We studied the effects that lesions produced in the paraventricular and suprachiasmatic nuclei and intervening periventricular area had on 24 h mean circadian blood pressures in Dahl salt-sensitive and -resistant rats and their sham-operated controls. We measured blood pressures while the animals were on a low salt diet and after 1, 5 and 13 weeks of 8% NaCl diet.

2. Salt-sensitive rats with lesions had lower blood pressures than salt-sensitive sham-operated controls at all points of the study. In contrast, identical lesions in salt-resistant rats produced a transient pressor response to the diet. Twenty-four hour mean heart rate, determined after 13 weeks of 8% NaCl intake, was low only in salt-sensitive rats with lesions. Sodium intake and excretion per kg of body weight, as well as plasma sodium concentrations, were similar in all groups.

3. We conclude that the anteromedial hypothalamic area, which includes the paraventricular nucleus, the suprachiasmatic nucleus and the intervening periventricular area, participates in the development of Dahl hypertension. We suggest that a multifactorial mechanism is involved: (a) the facilitatory role of this region in ACTH release, (b) this region's participation in the baroreceptor reflex via vasopressinergic efferents to the nucleus of the tractus solitarius, and (c) the roles of the paraventricular and suprachiasmatic nuclei in the regulation of salt and water balance.
Effect of Adrenalectomy on the Development of Isolation-Induced Hypertension in Rats
Authors: Gardiner S. M. , Milmer K. E. , Bennett T.
Published: August 2015

1. Male Wistar rats develop systolic arterial hypertension when housed in glass metabolism cages. The present experiments were designed to investigate the involvement of the adrenal glands in this form of hypertension.

2. Rats were bilaterally adrenalectomized and maintained by either salt supplementation (1% sodium chloride solution instead of tap water to drink) or steroid replacement (corticosterone solution in the drinking water).

3. Adrenalectomized rats treated as above did not develop hypertension in response to isolation, whereas sham-operated rats (drinking either 1% saline or tap water) did.

4. Hypertension in the sham-operated rats was not accompanied by a renal retention of sodium and water.

5. It is concluded that increased adrenal activity is involved in the development of isolation-induced hypertension, but not by causing a fluid retention and hence volume expansion. The relative contributions of adrenal medullary and cortical activity remain to be determined.
Accentuated Hypotensive Effect of Sodium Nitroprusside in Man after Captopril
Authors: Jennings G. L. , Gelman J. S. , Stockigt J. R. , Korner P. I.
Published: August 2015

1. The effects of graded intravenous infusions of sodium nitroprusside on resting blood pressure and heart rate and on the reflex changes in these variables evoked by a standardized Valsalva manoeuvre were studied in six normal subjects. The effects of nitroprusside on the above variables were also studied after pre-treatment with captopril, to allow assessment of the role of angiotensin II.

2. Nitroprusside given in doses ranging from 7.5 to 150 μg/min elicited dose-related decreases in resting blood pressure and rise in heart rate and in plasma renin activity (PRA). After pretreatment with captopril, nitroprusside could not be given at doses above 60 μg/min without producing an unacceptable fall in blood pressure. The rise in heart rate in response to a given dose of nitroprusside was little altered after captopril.

3. Blood pressure and heart rate were studied during the last 10 s of the Valsalva manoeuvre. Before captopril the normal response (maintenance of blood pressure with tachycardia) was not altered by any dose of nitroprusside. Captopril alone also had no effect on the response but, with captopril plus high dose nitroprusside, mean arterial pressure during the manoeuvre decreased significantly, indicating impairment of reflex constrictor response.

4. These findings support the proposition that the angiotensin II response normally limits the fall in blood pressure during vasodilator therapy. We conclude that the greater fall in blood pressure and the impaired constrictor response to the Valsalva manoeuvre during nitroprusside infusion at moderate doses, in the presence of captopril, is due to the effect of the latter on the renin—angiotensin system.

5. A practical consequence of the present findings is that combined use of captopril and arterial vasodilators requires reduction in the dose of the latter drug. Awareness of this interaction may avert hypotension and could also allow nitroprusside infusion for longer periods without toxicity.
Chemical Denervation Does Not Affect the Medial Hypertrophy and Increased Calcium Sensitivity of Mesenteric Resistance Vessels from Spontaneously Hypertensive Rats
Authors: Mulvany M. J. , Korsgaard N. , Nyborg N. , Nilsson H.
Published: August 2015

1. The properties of isolated 150-μm mesenteric resistance vessels from chemically denervated 5-month spontaneously hypertensive and normotensive Wistar—Kyoto rats have been examined.

2. Chemical denervation reduced the blood pressure of both strains of rats, but the denervated spontaneously hypertensive rats were still hypertensive with respect to their denervated Wistar—Kyoto controls.

3. Chemical denervation did not affect the morphological characteristics or calcium sensitivity of the resistance vessels.

4. The results suggest that the media hypertrophy and increased calcium sensitivity seen in resistance vessels from non-denervated spontaneously hypertensive rats are intrinsic defects unrelated to either blood pressure or neurogenic influences.
A Comparison of Physical Characteristics of Active Renin Isolated from Aorta, Plasma and Kidney of the Rat
Authors: Barrett J. D. , Eggena P. , Krall J. F. , Sambhi M. P.
Published: August 2015

1. Renin-like enzymes have been isolated from aorta, plasma and kidney tissue of the rat. The enzymes have been compared with respect to pH optima, molecular weight and isoelectric points.

2. Two distinct molecular-weight forms were isolated from plasma. The high-molecular-weight enzyme (mol. wt. > 150 000) appeared to be homogeneous with respect to isoelectric point (pI = 5.3), whereas the dominant lower-molecular-weight form (mol. wt. 44 000) demonstrated isoelectric heterogeneity.

3. The renin-like enzyme isolated from aortic tissue has mol. wt. 44 000 and also demonstrated isoelectric heterogeneity (pI = 5.0, 5.3). Plasma renin was significantly reduced after bilateral nephrectomy (30 h); however, the activity and relative proportions of the two aortic enzymes were not significantly altered.

4. Renin, isolated from kidney homogenates, either in the presence or absence of a variety of proteolytic enzyme inhibitors, had a significantly lower molecular weight (38 000) than the plasma enzyme but demonstrated a similar pattern of isoelectric heterogeneity.

5. in contrast with renin extracted from kidney, approximately 30% of the renin released from kidney cortical slices into Krebs-Ringer bicarbonate had mol. wt. 44 000. Only the 38 000 mol. wt. form was detected after storage of this medium and no change in total renin activity was evident. This suggests that the 38 000 mol. wt. form may be a methodological artifact due to the release of other proteolytic enzymes.

6. With homologous substrate, all fractionated enzymes showed a pH optimum between pH 7.0 and 7.5.

7. The present study indicates that the predominant form of renin released from rat kidney into blood has mol. wt. 44 000. The microheterogeneity of the plasma enzyme with respect to isoelectric point is similar to that of kidney renin. One form of renin (mol. wt. 44 000, pI = 5.0) may be common to kidney, plasma and aorta. The second aortic enzyme (pI = 5.3), however, may be of local origin.
Partial Replacement of Sodium by Potassium in the Diet Restores Impaired Noradrenaline Inactivation and Lowers Blood Pressure in Stroke-Prone Spontaneously Hypertensive Rats
Authors: Dietz R. , Schömig A. , Rascher W. , Strasser R. , Ganten U. , Kübler W.
Published: August 2015

1. Partial replacement of sodium by potassium in the diet attenuates the rise in blood pressure in stroke-prone spontaneously hypertensive rats (SHR-SP).

2. The blood pressure-lowering effect of potassium cannot be ascribed to a reduction in intravascular volume.

3. The increased dietary intake of potassium leads to a reduced stimulation of the sympathoneuronal and sympathoadrenal system by cold compared with the response of sodium-loaded rats.

4. The impaired inactivation of noradrenaline observed in sodium-loaded SHR-SP is improved in SHR-SP on a potassium-substituted diet.

5. It is concluded that changes in dietary intake of sodium and potassium modulate sympathetic activity and the metabolism of noradrenaline, both of which are related to the development of hypertension in SHR-SP.
Peritubular Interaction of Unconjugated Bilirubin in Isolated Perfused Rat Kidney
Authors: Elias Maria Monica , Comin E. J. , Galeazzi Susana , Garay E. A. Rodriguez
Published: August 2015

1. the interaction of unconjugated bilirubin with peritubular cell membranes of the rat kidney was studied by means of an isolated rat-kidney preparation applying the multiple-indicator-dilution technique.

2. Inulin was used as an extracellular marker and p-aminohippuric acid as a model of organic anion that interacts with the peritubular membrane.

3. A single renal artery injection of a mixture containing inulin and unconjugated bilirubin was followed by the appearance of the two compounds in the venous effluent. the unconjugated bilirubin curve was always under the curve of inulin and its mean transit time was always less than that for inulin.

4. the cumulative venous recovery of inulin was higher than that of unconjugated bilirubin.

5. When unconjugated bilirubin uptake was plotted against the injected dose of pigment the relationship suggested a saturation phenomenon.

6. the recovery of p-aminohippuric acid was significantly increased when unconjugated bilirubin was added.

7. the results provide evidence for the interaction of unconjugated bilirubin with the peritubular cell membranes of rat kidney.
Kassinin and Substance P Stimulate Somatostatin Release in the Rat
Authors: Güllner H.-G. , Harris Virginia , Unger R. H.
Published: August 2015

1. the effect of the tachykinin dodecapeptide kassinin, which has been extracted from the skin of several African frogs, on somatostatin release was examined in the rat and compared with that of the neuropeptide substance P.

2. Equimolar doses of the two peptides were injected intravenously and the animals killed at specified intervals after injection. Somatostatin was measured by a specific radioimmunoassay.

3. Kassinin and substance P had no effect when given in low doses (0.1 and 1.0 μg). However, when administered in a dose of 10.0 μg, both peptides significantly increased plasma somatostatin, by 31 and 22% respectively.

4. These findings suggest that kassinin and substance P have common endocrine actions. the effect on somatostatin release may be specific for tachykinins, since other neuropeptides such as the enkephalins have no effect.
Possible Relationship between Psycho-Emotional Factors and Haemodynamic Patterns in the Pathogenesis of Mild Blood Pressure Elevation
Authors: Jern S. , Sivertsson R. , Hansson L.
Published: August 2015

1. Psycho-emotional profiles were compared with invasive haemodynamic findings in a population sample of 37 young men (mean age 27 years) with mild blood pressure elevation and in 21 matched normotensive controls.

2. In comparison with normotensive controls, subjects with hyperkinetic blood pressure elevation had higher irritability levels, more guilt feelings and more psychic distressful symptoms.

3. In subjects with blood pressure elevation and normokinetic circulation structural vascular changes were found, and their psycho-emotional profiles showed high irritability levels but not significantly increased guilt or anxiety.

4. These results indicate a relationship between psychological factors and haemodynamic patterns in mild blood pressure elevation. A psychosomatic aetiology in hyperkinetic blood pressure elevation is suggested, and the psychological findings are compatible with a gradual development from hyperkinetic to normokinetic blood pressure elevation.
Vasopressin-Induced Increase in Total Peripheral Resistance in Deoxycorticosterone Acetate Hypertensive Rats is Buffered by the Baroreceptor Reflex
Authors: Rascher W. , Lang R. E. , Taubitz M. , Meffle H. , Unger TH. , Ganten D. , Gross F.
Published: August 2015

1. The role of arginine-vasopressin (AVP) in the maintenance of high blood pressure in rats with deoxycorticosterone acetate (DOCA) hypertension was investigated.

2. Plasma concentrations of AVP were significantly elevated in DOCA hypertensive rats compared with normotensive control rats, whether or not they received 1% sodium chloride solution or demineralized water to drink.

3. The specific antagonist of the vasopressor response to AVP, d(CH2)5VDAVP (100 μg/kg intravenously), significantly increased cardiac output and decreased total peripheral resistance, but had no effect on mean arterial pressure in DOCA hypertensive rats. No changes of mean arterial pressure, cardiac output and total peripheral resistance were observed in the normotensive control groups after d(CH2)5VDAVP.

4. After sino-aortic baroreceptor deafferentation, d(CH2)5VDAVP decreased mean arterial pressure in DOCA—salt hypertensive rats, but not in the control groups.

5. It is concluded that elevated circulating AVP causes vasoconstriction in DOCA hypertensive rats. The AVP-induced increase in total peripheral resistance is counter-regulated by an activation of the baroreceptor reflex and subsequent reduction in cardiac output.
Adrenaline-Induced Hypertension in Rats
Authors: Tung L.-H. , Rand M. J. , Majewski H.
Published: August 2015

1. Rats implanted with osmotic minipumps delivering adrenaline intraperitoneally at the rate of 2.9 nmol/h had significantly higher systolic and diastolic pressures from days 2 to 6 after implantation than sham-operated control rats.

2. Concomitant treatment with metoprolol tartrate (2.5 mg/kg, intraperitoneally, twice daily) prevented the elevation in blood pressure induced by adrenaline from osmotic minipumps. Such metoprolol treatment did not affect the blood pressure of control rats.

3. Noradrenaline administered intraperitoneally from osmotic minipumps at the rate of 2.9 nmol/h had no significant effect on blood pressure over a 6-day period of observation.

4. Tachyphylaxis developed to the acute pressor responses to intermittent intravenous infusions of adrenaline in doses of 0.78 μg (4.24 nmol) every 10 min, but after 14 days of such treatment systolic and diastolic blood pressures were significantly greater than in control rats.

5. It is suggested that the increase in blood pressure produced by chronic treatment with adrenaline is due to the uptake and accumulation of adrenaline in noradrenergic nerve terminals, from which it is subsequently released as a cotransmitter that mediates a positive feedback loop on, transmission by acting on prejunctional β-adrenoceptors.
Plasma Concentrations of Catecholamines in Two Strains of Spontaneously Hypertensive Rats at Different Ages
Authors: Ferrari P. , Picotti G. B. , Minotti E. , Bondiolotti G. P. , Caravaggi A. M. , Bianchi G.
Published: August 2015

1. Blood pressure was measured and plasma levels of noradrenaline and adrenaline were determined radioenzymatically under basal conditions and after 10% blood volume reduction in blood drawn through catheters previously implanted in young and adult rats of two different genetically hypertensive strains: the Kyoto strain (SHR) and the Milan strain (MHS), and in their respective controls: Wistar—Kyoto strain (WKY) and Milan normotensive strain (MNS).

2. Under basal conditions no differences were observed between plasma noradrenaline and adrenaline levels in SHR and MHS rats and in the controls, at any age. Haemorrhage produced a greater fall in the blood pressure (P < 0.01) of young and adult hypertensive strains (SHR-MHS) than in WKY and MNS rats, and a greater rise in plasma adrenaline (P < 0.01).

3. These results suggest that: (a) there may be differences in involvement of the sympathetic nervous system in the pathogenesis of hypertension in SHR and MHS rats but not such as to cause differences in plasma catecholamine levels in either young or adult rats; (b) haemorrhage activates the sympatho—adrenal systems more in SHR and MHS rats, than in controls, and the greater percentage fall in blood pressure is probably due to a difference in reflex venoconstriction.
Noradrenaline Reactivity in Patients with Phaeochromocytoma before and after Surgical Correction
Authors: Leonetti G. , Terzoli L. , Bianchini G. , Rupoli L. , Lipira R. , Zanchetti A.
Published: August 2015

1. For comparable blood pressures, plasma noradrenaline is disproportionately higher in patients with phaeochromocytoma than in those with essential hypertension.

2. The ‘pressor-dose’ of noradrenaline or its reciprocal, the reactivity index, were abnormal in patients with phaeochromocytoma before surgery and made normal by surgical removal of the phaeochromocytoma.

3. There was a significant correlation between blood pressures and the logarithm of plasma noradrenaline concentrations.

4. The higher dose of exogenous noradrenaline required in patients with phaeochromocytoma for a given rise in blood pressure seems to be the expression of the higher levels of endogenous noradrenaline rather than true decreased reactivity.
Differences In Utero in Activities of Catecholamine Biosynthetic Enzymes in Adrenals of Spontaneously Hypertensive Rats
Authors: Teitelman G. , Ross R. A. , Joh T. H. , Reis D. J.
Published: August 2015

1. We sought to determine if catecholamine biosynthetic enzymes of spontaneously hypertensive rats (SHR) differed from those of normotensive Wistar—Kyoto (WKY) and Sprague—Dawley (SD) control rats before birth.

2. By immunocytochemical and biochemical methods we compared strains for the time of appearance and maturation of the enzymes tyrosine hydroylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) in sympathetic ganglia and adrenals.

3. The time of appearance of enzymes was identical in all three strains: TH and DBH first appeared in sympathetic ganglia on embryonic day 11 (E11) and in adrenal medulla on E16. PNMT, restricted to adrenal medulla, appeared later on E18.

4. The activity of adrenal TH prenatally on E18 and E21 and at day of birth (P1) in SHR was approximately two fold that in WKY or SD rats. In contrast PNMT was lower in SHR but only on E18.

5. Thus, although the timing of the first expression of adrenergic phenotypes is similar in SHR and normotensive controls, the differences in TH activity in adrenals suggest an enhanced biosynthetic capacity for catecholamines in this strain before birth.

6. We conclude that SHR differ from normotensive rats from the first expression of some of the genes controlling catecholamine biosynthesis.
Central Dopaminergic Mechanisms in Young Patients with Essential Hypertension
Authors: Kolloch R. E. , Stumpe K. O. , Ismer U. , Kletzky O. , Dequattro V.
Published: August 2015

1. Central dopaminergic pathways are possibly related to noradrenergic tone and may be important in the pathogenesis of essential hypertension. Basal plasma prolactin levels have been used as a marker of dopaminergic activity in the hypothalamus. The prolactin response to thyrotropin-releasing hormone (TRH) gives evidence of the dynamics of prolactin secretion.

2. To evaluate further the role of dopaminergic mechanisms in hypertension three groups of young male hypertensive patients were studied and compared with healthy male volunteers. In group 1 prolactin secretion was evaluated overnight at 60 min intervals from 22.00 to 06.00 hours. In group 2 we measured plasma prolactin concentrations before and sequentially after intravenous injection of 200 μg of TRH. In group 3 we measured prolactin, plasma and urinary noradrenaline and normetadrenaline during various degrees of physical and mental activity.

3. Basal prolactin, noradrenaline and normetadrenaline levels were higher in the hypertensive patients as compared with normotensive controls. In the hypertensive patients the prolactin response to TRH was significantly attenuated. Treatment with bromocriptine, a centrally acting dopaminergic agonist, lowered the blood pressure and suppressed the elevated prolactin and noradrenaline levels in the hypertensive patients. During bromocriptine therapy the prolactin response to TRH was not different in normotensive and hypertensive subjects.

4. These results suggest an abnormal regulation of the prolactin secretion in young hypertensive patients with evidence of increased sympathetic tone, supporting the concept that central dopaminergic mechanisms may be involved in the development or maintenance of essential hypertension.
Studies of the Biosynthesis of Renin with a Cell-Free Translation System
Authors: Dzau V. J. , Ouellette A. , Pratt R.
Published: August 2015

1. Poly(A)+ mRNA from mouse submaxillary gland encodes a polypeptide of molecular weight 48 000 (48K polypeptide) which is abundant in the male.

2. This polypeptide is selectively absent in the translation products of mRNA from a strain of genetically renin-deficient mice C57 BL/10J.

3. The 48K polypeptide binds and co-elutes in identical fashion with pure authentic renin on pepstatin affinity chromatography.

4. Immunoprecipitation of translation products of male glandular mRNA with renin-specific antibody yielded this 48K band upon analysis by SDS/polyacrylamide gel electrophoresis and fluorography. Pure renin of molecular weight 37 000 blocked the binding of this polypeptide to antirenin antibody.

5. Mouse submaxillary gland synthesizes a renin precursor. The renin mRNA is androgenically regulated.
Specific Nuclear Binding of Angiotensin II by Rat Liver and Spleen Nuclei
Authors: Re R. N. , MacPhee A. A. , Fallon J. T.
Published: August 2015

1. Nuclei were isolated from rat liver and spleen by a standard technique which preserved the nuclear membrane. Electron microscopy, DNA/protein ratios and 5′-nucleotidase determinations confirmed the purity of the preparation.

2. Both liver and spleen nuclei specifically bound 125I-labelled angiotensin II (ANG II) with high affinity (Kd ≅ 1.0 nmol/l). Saralasin ANG III and ANG II competed with tracer for ligand whereas ANG I did so less effectively and neurotensin not at all.

3. These results suggest the presence of specific nuclear intracellular ANG II receptors and raise important questions regarding the mechanism of action of this peptide.
Blood Pressure and the Renin—Angiotensin—Aldosterone System
Authors: Ljungman S. , Aurell M. , Hartford M. , Wikstrand J. , Berglund G.
Published: August 2015

1. The relationships between blood pressure and the components of the renin-angiotensin-aldosterone system were studied in 49-year-old men (n = 120) who were selected at random from the total population so as to be representative of all blood pressure levels.

2. Only plasma aldosterone concentration was significantly correlated with blood pressure, both in the whole study group (r = 0.22; P < 0.02) and in the hypertensive blood pressure range (r = 0.36; P < 0.02). The hypertensive subjects had a significantly higher plasma aldosterone concentration than the borderline and normotensive subjects.

3. Multiple regression analysis including factors related to the renin—angiotensin—aldosterone system, showed that the 24 h urinary excretion of noradrenaline was the factor most strongly correlated to. plasma aldosterone.

4. The findings indicate that aldosterone may be the most important component of the renin—angiotensin—aldosterone system in the development and maintenance of essential hypertension.
Effects of the Oral Angiotensin-Converting Enzyme Inhibitor MK-421 in Human Hypertension
Authors: Gavras H. , Biollaz J. , Waeber B. , Brunner H. R. , Irene Gavras , Sackel H. , Charocopos F. , Davies R. O.
Published: August 2015

1. The effects of the new oral angiotensin-converting enzyme (ACE) inhibitor MK-421 on blood pressure, plasma renin activity, angiotensin II, aldosterone and converting enzyme activity were assessed in 16 hypertensive patients followed for 6–18 weeks.

2. After an initial titration period, maintenance doses of 2.5–40 mg once daily produced satisfactory blood pressure control in 11 and a partial but significant decrease in the remainder.

3. Treatment was associated with no change in heart rate and no orthostatic hypotension. At 24 h after the first effective dose, blood pressure was still decreased, plasma ACE was suppressed to 16% of the baseline, plasma angiotensin to 58%, aldosterone to 42%, and plasma renin activity was elevated to 228% of the baseline.

4. Magnitude of blood pressure fall was significantly correlated with the height of pretreatment blood pressure but not with baseline levels of plasma renin activity.
Vasodepressor Effects of Arachidonic Acid and Prostacyclin (PGI2) in Hypertensive Rats
Authors: Dusting G. J. , Di Nicolantonio R. , Drysdale T. , Doyle A. E.
Published: August 2015

1. Vasodepressor responses to prostacyclin and nitroprusside were compared in anaesthetized, spontaneously hypertensive rats of the Okamoto strain and Wistar—Kyoto controls, and also in one-kidney, one-clip hypertensive rats and unilaterally nephrectomized controls of the Sprague—Dawley strain. The responses, measured as a percentage of resting blood pressure, did not differ significantly between the hypertensive rats and the normotensive controls within each strain.

2. The effects of intravenous injections of arachidonic acid were also studied in each strain.

3. The vasodepressor effects of high doses of arachidonic acid (1 or 3 mg/kg) were much greater and more prolonged in both groups of hypertensive rats. These differences were abolished by indomethacin (2 mg/kg).

4. Comparisons between the strains showed that whereas Okamoto rats have significantly greater depressor responsiveness to nitroprusside and prostacyclin than Sprague—Dawley rats, the depressor effects of high doses of arachidonic acid (1 and 3 mg/kg) were smaller in the normotensive Wistar-Kyoto than in the Sprague—Dawley rats.

5. It is concluded that hypertensive rats have enhanced ability to transform exogenous arachidonic acid into vasodilator prostanoids. This occurs both in spontaneous hypertension and in experimental renal hypertension. However, rats of the Okamoto strain appear to have reduced ability to form prostacyclin when compared with Sprague—Dawley rats.
Central Haemodynamics and Plasma Prostaglandin E2 in Borderline and Sustained Essential Hypertensive Patients before and after Indomethacin
Authors: Safar M. E. , Hornych A. F. , Levenson J. A. , Simon A. Ch. , London G. M. , Bariéty J. L. , Milliez P. L.
Published: August 2015

1. In basal conditions, plasma arterial prostaglandin (PG) E2 was significantly increased in borderline hypertensive patients (BH) (28.5 ± 6.7 pg/ml) in comparison with sustained essential hypertensive patients (EH) (11.6 ± 3.2 pg/ml) and in comparison with control normotensive subjects (NTS) (5.8 ± 1.4 pg/ml).

2. Plasma arterial PGE2 was positively significantly correlated with cardiac index and negatively significantly correlated with total peripheral resistance in basal conditions.

3. Indomethacin induced more pronounced haemodynamic changes in borderline than in sustained hypertensive patients, with a significant increase in arterial blood pressure and total peripheral resistance and a significant decrease in stroke volume and cardiac index.

4. Indomethacin significantly decreased arterial PGE2 in borderline hypertensive patients. The decrease was less important in sustained hypertensive patients.

5. In the overall population, a significant positive correlation between arterial PGE2 concentration and cardiac index was observed before and after indomethacin treatment.

6. The study suggests an important role of PGE2 in the regulation of cardiac output (positive inotropic effect) and blood pressure of essential hypertensive patients.
Association between the C3F-Gene and Essential Hypertension
Authors: Schaadt O. , Sørensen H. , Krogsgaard A. R.
Published: August 2015

1. The complement 3 (C3) phenotype distribution in 112 patients with essential hypertension was compared with the distributtion in 316 normotensive control subjects.

2. A significant increased frequency of the C3F-gene was found among the patients (0.2637 vs 0.1721, P = 0.0031), indicating an association between the C3F-gene and essential hypertension.

3. The relative risk of essential hypertension was calculated to be 1.90 for C3F-positive individuals.

4. The association between the C3F-gene and essential hypertension was stronger among the untreated patients, where a relative risk of 3.89 was found for C3F-positive subjects.

5. A significant negative correlation was found between the C3F-positivity and the severity of the hypertensive disease estimated by eye ground changes. This might be in accordance with a negative natural selection of C3F-positive hypertensive patients.

6. The study supports the hypothesis that immunogenetic factors may be of pathogenetic importance in essential hypertension.
Anger, Anxiety, Guilt and Increased Basal and Stress-Induced Neurogenic Tone: Causes or Effects in Primary Hypertension?
Authors: Sullivan P. A. , Procci W. R. , DeQuattro V. , Schoentgen Sarah , Levine D. , Van Der Meulen J. , Bornheimer J. F.
Published: August 2015

1. Basal plasma and spinal fluid noradrenaline were increased in patients with primary hypertension and phaeochromocytoma compared with normotensive patients (P < 0.01).

2. Patients with primary hypertension had more anger (P < 0.01), anxiety (P < 0.01) and guilt (P < 0.05) than normotensive patients or patients with phaeochromocytoma.

3. The responses of noradrenaline and adrenaline concentrations were similar after mental and isometric stress in primary hypertensive and normotensive subjects.

4. However, after mental stress and isometric exercise there were increased responses of plasma noradrenaline and systolic blood pressure respectively, in patients with high anxiety and anger compared with those below the 50th percentile (P < 0.05).

5. Increased central and peripheral neurogenic tone at rest and after stress in association with increased anxiety and suppressed anger appear to be pathogenic factors in some patients with primary hypertension and may not be a result of the blood pressure elevation.
Response of Patients with Renal Involvement by Progressive Systemic Sclerosis to Antihypertensive Therapy
Authors: Traub Y. M. , Shapiro A. P. , Osial T. A. , Rodnan G. P. , Medsger T. A. , Leb D. E. , Christy W. C.
Published: August 2015

1. Renal involvement in progressive systemic sclerosis is characterized by hypertension, grade III or IV hypertensive retinopathy, rapidly progressive renal failure and enhanced plasma renin activity.

2. Of 70 patients with progressive systemic sclerosis involving the kidneys seen since 1955, 48 died within less than 3 months and 16 are alive or survived longer than 1 year.

3. Aggressive antihypertensive therapy was the principal factor that prevented early death in the 16 survivors.

4. Angiotensin converting enzyme inhibition with captopril appears to be the treatment of choice at present, but methyldopa or minoxidil may be successful in certain patients whose response to captopril is not satisfactory.
The Hypotensive Effect of Propranolol in Captopril-Treated Patients Does Not Involve the Plasma Renin—Angiotensin—Aldosterone System
Authors: Staessen J. , Fagard R. , Lijnen P. , Verschueren L. J. , Amery A.
Published: August 2015

1. With a double-blind cross-over protocol, 20 hypertensive captopril-treated patients were studied by adding in a variable sequence a placebo and propranolol (80 mg three times a day) to their captopril regimen (200 mg three times a day), during periods each lasting 1 month. During captopril—placebo treatment their diastolic blood pressure remained elevated between 90 and 114 mmHg.

2. The additional administration of propranolol produced a significant hypotensive effect, but no alterations of the plasma angiotensin II and aldosterone concentrations and of the urinary aldosterone excretion occurred. The present data indicate that in captopril-treated patients the hypotensive effect of propranolol is achieved independently of changes in the plasma angiotensin II and aldosterone concentration.

3. The additional administration of propranolol also produced an increase in the serum potassium levels in the absence of any change in the plasma aldosterone concentration or in the urinary aldosterone excretion.
The Effect of Oral Prazosin on Blood Pressure and Plasma Concentrations of Renin and Angiotensin II in Man
Authors: McAreavey D. , Cumming A. M. M. , Sood V. P. , Leckie B. J. , Morton J. J. , Murray G. D. , Robertson J. I. S.
Published: August 2015

1. We studied the effect of oral prazosin on blood pressure, plasma active renin and angiotensin II in 16 recumbent hypertensive patients between 09.00 and 12.00 hours.

2. In untreated patients there were no significant changes in blood pressure, plasma active renin or angiotensin II during the 3 h period.

3. After an initial dose of prazosin (2 mg) there was a significant fall in recumbent blood pressure with progressive increases in plasma active renin and angiotensin II concentrations.

4. After 3–4 weeks' treatment with oral prazosin only, recumbent blood pressure at 09.00 hours, 15 h after the last dose of prazosin, was significantly lower than before treatment, but plasma active renin and angiotensin II were not significantly different from untreated values.

5. After the usual morning dose of prazosin, blood pressure did not change, but there were significant rises in plasma active renin and angiotensin II, less marked than after the first dose of prazosin.

6. Prazosin therefore stimulates the renin—angiotensin system acutely, both after the initial dose and during long-term therapy; however, no effect on renin and angiotensin II is apparent 15 h after the last dose of prazosin.
Fibrin Deposition in the Kidney and Renal Blood Flow during Intravascular Coagulation in the Rat: Influence of the Renin–Angiotensin System
Authors: Ståhl E. , Karlberg B. E. , Rammer L.
Published: August 2015

1. Intravascular coagulation in the kidneys of rats was induced by intravenous infusion of thrombin and by inhibition of fibrinolysis with tranexamic acid under α-chloralose anaesthesia. The amount of fibrin in the kidneys was measured with radioactively labelled fibrinogen. Chronic saline loading and inhibition of angiotensin II (ANG II) with saralasin reduced the fibrin deposition in the kidneys. Infusion of ANG II had the opposite effect.

2. Renal and aortic blood flows were measured by injection of radioactively labelled microspheres. After thrombin infusion the renal and aortic blood flows were reduced to about one-third of the pre-infusion values. Chronic saline loading diminished these changes, but saralasin had no effect.

3. Plasma renin activity (PRA), measured by radioimmunoassay, decreased by about 50% after thrombin infusion.

4. The reduction in PRA and the lack of effect of saralasin indicate that the renin—angiotensin system is not the mediator of the observed decrease in the renal blood flow. As saralasin reduced the amount of fibrin the mechanism regulating fibrin deposition appears to be independent of the mechanism that reduces the renal blood flow.