bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on the Hypotensive Effect of High Potassium Intake in Patients with Essential Hypertension
Authors: Iimura Osamu , Kijima Toshiaki , Kikuchi Kenjiro , Miyama Akiyoshi , Ando Toshiaki , Nakao Takashi , Takigami Yoshiichi
Published: August 2015

1. In order to confirm and investigate the hypotensive effect of a high potassium intake we compared mean arterial pressure (MAP), water and electrolyte balance, plasma and urinary noradrenaline (NA), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in 20 inpatients with mild or moderate essential hypertension on a control diet (Na: 260, K: 75 mmol/day), and after high (K: 175 mmol/day) and low potassium diets (K: 25 mmol/day).

2. After potassium loading, urinary volume (UV) and urinary excretion of sodium (UNaV) and of potassium (UKV) were elevated, and MAP, body weight, plasma volume (PV), extracellular fluid volume (ECFV) and total exchangeable sodium (Nae) were reduced significantly.

3. After potassium loading, PRA, PAC, plasma and urinary NA increased and the pressor response to infused noradrenaline and angiotensin II decreased significantly.

4. The reduction of MAP after potassium loading correlated positively with PV and ECFV during the control period. In addition, significant correlations were found between ΔUV and ΔUNaV, —ΔPV and ΔU/NaV, —ΔPV and Δ plasma NA, and Δ plasma NA and Δ PRA.

5. Patients with low PRA had high PV, ECFV and Nae during the control period, and showed greater reductions of MAP, PV, ECFV and Nae after potassium loading.

6. After potassium restriction, UNaV, PRA and urinary NA decreased and PV increased, and MAP did not change significantly.

7. These results suggest that the hypotensive effect of high potassium intake may be caused by reduction of body fluid volume via augmentation of Na excretion.
Substrate Oxidation Shortly after Accidental Injury in Man
Authors: Little R. A. , Stoner H. B. , Frayn K. N.
Published: August 2015

1. Oxidative metabolism has been studied by indirect calorimetry in 42 patients within the first 6 h after accidental injury.

2. the level of energy expenditure bore no relationship to the severity of the injury and varied more widely from patient to patient than in normal subjects.

3. After minor and moderate injuries the respiratory exchange ratio (mean 0.86) was not different from that in normal subjects on a mixed diet. After severe injuries the ratio (mean 0.78) was significantly lower (P < 0.005), indicating that the main substrate for oxidation in these patients was fat, despite their hyperglycaemia.
Left Ventricular Hypertrophy Improves Cardiac Function in Spontaneously Hypertensive Rats
Authors: Lundin S. , Friberg P. , Hallbäck-Nordlander Margareta
Published: August 2015

1. The influence of different arterial pressures on the relationship between diastolic filling pressure and stroke volume was studied during pharmacological cardiac nerve blockade in adult, anaesthetized spontaneously hypertensive rats in comparison with matched normotensive Wistar—Kyoto rats.

2. Peak stroke volumes, obtained by rapid blood volume expansion were similar in both types of rat, despite a more than 40% higher mean arterial pressure in the spontaneously hypertensive rats.

3. When peak stroke volumes were compared in the two groups at equal ‘normotensive’ or ‘hypertensive’ arterial pressures, they were always greater in the spontaneously hypertensive rats.

4. Calculation of diastolic wall/lumen ratios indicated that the increase of maximal stroke work in the spontaneously hypertensive rats closely matched the hypertrophic increase in wall/lumen ratio of the left ventricle.

5. These results indicate that left ventricular hypertrophy in established primary hypertension is a physiological adaptation to match left ventricular performance to the raised afterload.
Extent of Structurally Reduced Venous Distensibility in Rats
Authors: Nilsson Holger , Haraldsson Börje , Folkow Björn
Published: August 2015

1. Venous pressure-volume relations were studied in maximally vasodilated whole-body preparations after cardiac arrest, as well as in fully vasodilated, perfused hindquarter preparations of spontaneously hypertensive rats (SHR) and normotensive controls. Central venous pressures were measured also in the anaesthetized animals before cardiac arrest.

2. Central venous pressure in intact, anaesthetized SHR was 1.9 ± 0.20 mmHg compared with 0.75 ± 0.25 in controls (P < 0.001).

3. In both preparations SHR showed a nearly 20% reduction in venous compliance, whereas calculated ‘unstressed’ volumes (volumes at zero transmural pressure) were largely equal in SHR and controls.

4. SHR capacitance vessels thus appear to have a structurally reduced wall distensibility of about 10% with no change in overall size. It probably reflects a structural adaptation to a modest increase of average transmural pressure that also affects the low-pressure side.
Does Vasopressin Play a Role in the Pathogenesis of Hypertension?
Authors: Padfield P. L. , Brown J. J. , Lever A. F. , Morton J. J. , Robertson J. I. S.
Published: August 2015

1. Plasma levels of vasopressin were found to be significantly higher in 29 patients with malignant hypertension than in 106 normotensive control subjects (13 ± 2 ng/l vs 5.8 ± 0.2 ng/l, P < 0.001).

2. No correlation was apparent between blood pressure and circulating vasopressin.

3. An acute, incremental infusion of vasopressin (0.125, 0.25 and 0.5 ng min−1 kg−1) in nine patients with mild-moderate essential hypertension produced only minor changes in blood pressure despite achieving plasma levels spanning those seen in malignant hypertension.

4. Despite a small increase in pressor sensitivity to vasopressin in hypertensive subjects it is thus unlikely that an acute vasoconstrictor effect of this peptide is important in the pathogenesis of malignant hypertension.
The Reflex Control of Arginine-Vasopressin Release in Essential Hypertension
Authors: Ricciardelli B. , Volpe M. , Trimarco B. , Chiariello M. , Rengo F. , Condorelli Mario
Published: August 2015

1. The reflex control of arginine-vasopressin release was studied in 12 essential established hypertensive patients and in 12 age-matched normal subjects by comparing the effects of head-up tilt and a variable-pressure neck-chamber.

2. After 45 min 85° head-up tilt, normal subjects showed an increase in plasma arginine-vasopressin and in plasma renin activity, while plasma volume decreased. In hypertensive patients, plasma arginine-vasopressin showed changes after tilt opposite to those of controls, while the changes in plasma renin activity and plasma volume were similar to those observed in the normal group. In both groups the changes in systolic and diastolic blood pressure were not statistically significant. A reduction in carotid sinus transmural pressure obtained by increasing neck-tissue pressure (+ 50 mmHg) by means of a neck-chamber, evoked different responses in mean blood pressure in the two groups, but failed to induce any significant change in plasma arginine-vasopressin concentration both in the normal and in the hypertensive subjects.

3. These results seem to suggest that carotid sinus baroreceptors, though active in blood pressure control, do not play a direct role in arginine-vasopressin release and, therefore, the opposite response of arginine-vasopressin observed after tilt in the two groups of subjects should be ascribed to more complex mechanisms.
Abnormalities and Drug-Induced Alterations of Vasopressin in Human Hypertension
Authors: Thibonnier M. , Aldigier J. C. , Soto M. E. , Sassano P. , Menard J. , Corvol P.
Published: August 2015

1. Plasma vasopressin was estimated in 20 normotensive, 46 moderate hypertensive and 14 severe hypertensive patients under normal sodium diet.

2. In moderate hypertensive patients basal values for plasma vasopressin (PVP) after overnight dehydration and 24 h urinary vasopressin (UVP) were respectively 1.82 ± 0.23 pmol/l and 44 ± 4 pmol/day, which were not different from those found in normal subjects (PVP = 1.14 ± 0.11 pmol/l and UVP = 54 ± 4 pmol/day). In contrast, basal values were significantly increased in severely hypertensive patients (PVP = 4.69 ± 1.45 pmol/l, P < 0.005; UVP = 107 ± 17 pmol/day, P < 0.01).

3. In a group of 12 moderately hypertensive patients the blood pressure reduction induced by a single 20 mg dose of nifedipine was associated with an increase in PVP from 1.48 ± 0.57 to 2.48 ± 0.74 pmol/l (P < 0.05) and in UVP from 42 ± 7 to 67 ± 17 pmol/day (P < 0.05). On the other hand, a single dose of captopril (1 mg/kg body weight) administered to the same patients did not alter PVP (1.68 ± 0.43 pmol/l) and UVP (40 ± 6 pmol/day) despite a similar blood pressure decrease.

4. In a group of 10 severely hypertensive patients, the blood pressure reduction induced by the first dose of captopril (1 mg/kg) was correlated to the pretreatment level of PVP (r = 0.89, P < 0.001) and of UVP (r = 0.70, P < 0.01). Eight days of captopril treatment reduced PVP from 5.24 ± 1.38 to 1.18 ± 0.32 pmol/l (P < 0.01) and UVP from 68 ± 17 to 25 ± 3 pmol/day (P < 0.001).

5. Increased levels of vasopressin are a marker of severe forms of hypertension. The reduction of vasopressin during captopril treatment could be an additional mechanism underlying the anti-hypertensive effect of that drug. Moreover, from the comparison between nifedipine and captopril, it appears that antihypertensive drugs have different effects on vasopressin release.
Daily Profile of Baroreflex Sensitivity and the Variability of Blood Pressure in Essential Hypertensive Patients
Authors: Ogawa Jun , Arai Shiro , Takata Shigeo , Ikeda Takayuki , Takabatake Toshikazu , Hattori Nobu , Nomura Gakuji
Published: August 2015

1. We have monitored intra-arterial pressure continuously throughout the day and analysed every beat by computer.

2. Baroreflex sensitivity (ms/mmHg) was measured four times a day (07.00, 12.00, 17.00 and 20.00 hours) in seven patients and three times a day (07.00, 12.00 and 17.00 hours) in 23 patients. The diurnal variation of baroreflex sensitivity in individual patients was 0–5.3 ms/mmHg and was not consistent. Mean baroreflex sensitivity was reduced in hypertensive patients compared with normotensive subjects.

3. A negative correlation was seen between baroreflex sensitivity and the variability of systolic blood pressure.

4. Baroreflex sensitivity was well correlated with the variability of heart rate.
Elevated Plasma Adrenaline Reflects Sympathetic Overactivity and Enhanced α-Adrenoceptor-Mediated Vasoconstriction in Essential Hypertension
Authors: Bolli P. , Amann F. W. , Hulthén L. , Kiowski W. , Bühler F. R.
Published: August 2015

1. Stressful sympathetic stimulation (cold pressor test) was applied to 18 patients with essential hypertension and 15 normotensive subjects. Intra-arterial blood pressure, heart rate, plasma adrenaline and noradrenaline concentrations as well as forearm blood flow were measured before and during the cold pressor test; tests were repeated after regional postsynaptic α1-adrenoceptor blockade with prazosin.

2. Under basal conditions mean blood pressure (P < 0.001), heart rate (P < 0.01), forearm blood flow (P < 0.001) as well as adrenaline concentration (P < 0.01), but not noradrenaline, was higher in patients with essential hypertension.

3. During the cold pressor test, mean blood pressure, heart rate, plasma adrenaline and noradrenaline concentrations increased and forearm flow decreased (all P < 0.001).

4. Stress-stimulated plasma adrenaline was higher in essential hypertensive patients than in normotensive subjects (P < 0.01). In the former the stress-induced increase in plasma adrenaline correlated with the increase in mean blood pressure (r = 0.514; P < 0.05).

5. Prazosin increased forearm blood flow more in essential hypertension (P < 0.001). This increase correlated with the resting plasma adrenaline in the hypertensive (r = 0.710; P < 0.001), but not in normotensive, subjects.

6. When the cold pressor test was repeated during postsynaptic α1-adrenoceptor blockade forearm blood flow did not decrease; instead it increased further in both groups (P < 0.05).

7. Thus in essential hypertension elevated plasma adrenaline concentration reflects sympathetic overactivity as also expressed by enhanced α-adrenoceptor-mediated vasoconstriction.
Blood Volume and the Carotid Baroreceptor Reflex in Conscious Rabbits
Authors: Ludbrook J. , Faris I. B. , Jamieson G. G.
Published: August 2015

1. The effects of acute blood volume change in conscious rabbits on a.c. gain of the carotid baroreceptor reflex with respect to heart rate, blood pressure, cardiac output and systemic vascular resistance were studied.

2. With acute, isohaemic increase in blood volume by 20% and 40% the only consistent trend was a decrease in gain for systemic vascular resistance.

3. With acute reduction in blood volume there was a consistent tendency for gain for heart rate to fall. With 20% reduction in blood volume, gain for cardiac output fell but gain for systemic vascular resistance rose and its phase-lag became shorter, so that gain for blood pressure was unaltered. The enhanced gain for systemic vascular resistance was not sustained with 35% reduction in blood volume, so that gain for blood pressure fell.

4. Thus control of blood pressure by the carotid sinus reflex is remarkably unaffected by acute change in blood volume, and is impaired only when there is depression of gain for cardiac output without a concomitant rise in gain for systemic vascular resistance.
Contribution of Cardiovascular Reflexes to Differences in β-Adrenoceptor-Mediated Responses in Essential Hypertension
Authors: Jennings G. , Bobik A. , Esler M. , Korner P.
Published: August 2015

1. The responses to stimulation of both cardiac and lymphocyte β-adrenoceptors were studied in 23 normal subjects and 23 with untreated essential hypertension. Lymphocyte cyclic adenosine monophosphate was measured in vitro after incubation with isoprenaline (0.01 μmol/l-10 mmol/l). There were no significant differences between the amount of cyclic adenosine monophosphate generated by lymphocytes in the two groups in the isoprenaline concentration range 0.01 μmol/l-1 mmol/l.

2. In the same subjects we compared cardiac β-adrenoceptor-mediated responses using the change in heart rate after bolus doses of isoprenaline (dose range 0.25–3 μg). In 12 subjects (six normotensive, six hypertensive) we studied the heart rate responses to isoprenaline before and after ‘total’ autonomic block (0.04 mg of atropine/kg and 300 μg of clonidine). The latter permitted assessment of intrinsic cardiac responsiveness after eliminating cardiovascular reflexes.

3. In subjects with reflexes intact the rise in heart rate was significantly greater in normal than in hypertensive subjects at all doses of isoprenaline. Isoprenaline evoked a similar dose-related fall in blood pressure in both groups, which contributed to the reflex drive. After autonomic block the differences in heart rate responses were no longer present.

4. The results indicate that the reduced tachycardia at a given dose of isoprenaline in hypertensive subjects is due to impairment in their baroreceptor—heart rate reflex since this was no longer present after atropine and clonidine.

5. The absence of any intrinsic difference in cardiac β-adrenoceptor responsiveness is in agreement with the results with lymphocytes.
Endogenous Agonist Regulation of α-Adrenoceptors in Man
Authors: Davies I. B. , Sudera D. , Sever P. S.
Published: August 2015

1. Plasma noradrenaline concentrations and platelet α-receptor properties were measured in 14 normal subjects, five phaeochromocytoma patients and nine patients with multiple system atrophy and sympathetic nervous system degeneration (MSA).

2. Plasma noradrenaline concentrations in phaeochromocytoma were 10- to 20-times greater than those of normal subjects and one-fifth to one-half of normal in MSA patients.

3. Platelet α-receptor numbers were increased in MSA and decreased in phaeochromocytoma compared with normal subjects. There was no change in platelet α-receptor affinity in either group.

4. The inverse relationship between α-receptor numbers and plasma noradrenaline concentrations may reflect regulation of α-receptor number by endogenous adrenergic agonist concentrations in man.
Role of Dopamine in the Regulation of Blood Pressure and the Renin—Angiotensin—Aldosterone System in Conscious Rats
Authors: Kondo Kazuoki , Ebihara Akio , Suzuki Hiromichi , Saruta Takao
Published: August 2015

1. In conscious rats, intracerebroventricular injection of dopamine resulted in a decrease in blood pressure, whereas injection of metoclopramide, the dopamine antagonist, produced an increase in blood pressure. The central depressor effect of dopamine was attenuated by a subpressor pretreatment with intraventricular metoclopramide, but not by phentolamine.

2. Intravenous administration of dopamine increased blood pressure. This increase in blood pressure was almost completely abolished by intravenous phentolamine. Metoclopramide, when injected intravenously, did not induce any change in blood pressure.

3. Plasma renin activity and plasma aldosterone concentration were decreased by intraventricular injection of dopamine, and increased by that of metoclopramide. In contrast, intravenous administration of metoclopramide increased plasma aldosterone concentration without changing plasma renin activity. Plasma concentrations of potassium, sodium and corticosterone were not affected by these treatments.

4. These results suggest that the dopaminergic system in the brain, but not in the systemic circulation, is involved in the regulation of blood pressure. It is also suggested that the central dopaminergic system participates in the regulation of aldosterone secretion by changes in the renin—angiotensin axis, whereas the peripheral dopaminergic modulation of aldosterone secretion appears to occur independently of the renin-angiotensin system.
Distribution and Properties of Angiotensin-Converting Enzyme in Cerebral Microvessels of the Rabbit and Rat
Authors: Brecher P. , Hingorani Vandana , Reininga Karen , Chobanian A. V.
Published: August 2015

1. Angiotensin-converting enzyme (ACE) activity was threefold greater in isolated cerebral microvessels obtained from rabbit brain than rat brain.

2. ACE activity was distributed throughout the cerebral microvasculature, since differences were not found between preparations enriched in capillaries as compared with those enriched in arterioles and venules.

3. Aortic tissue from rat and rabbit had little ACE activity compared with the microvessels.

4. ACE activity was tightly associated with endothelial cells and was not released by heparin under conditions where lipoprotein lipase was effectively removed.
Activation of Renin in An Anaplastic Pulmonary Adenocarcinoma
Authors: Soubrier F. , Skinner S. L. , Miyazaki M. , Genest J. , Menard J. , Corvol P.
Published: August 2015

1. Biochemical characteristics of a renin-like enzyme secreted by a pulmonary adenocarcinoma have been studied. A very high renin content was revealed by both enzymatic (10.4 Goldblatt units/g of tissue) and direct radioimmunoassay of immunoreactive renin (23 Goldblatt units/g of tissue).

2. The higher value by direct radioimmunoassay suggested the presence of an inactive form of the enzyme. Indeed 40–100% activation occurred with treatment by trypsin or pepsin or prolonged dialysis at pH 7.4 with or without prior acid dialysis. This neutral activation was completely abolished by a serine proteinase inhibitor.

3. A large fraction of the renin in this tumour is inactive. In comparison with other pro-hormones produced in tumours the findings support strongly the proposition that renin passes through a proenzyme step in synthesis.
Are Prostaglandins Involved in the Antihypertensive Effect of Dihydralazine?
Authors: Reimann Ingrid W. , Ratge D. , Wisser H. , Frölich J. C.
Published: August 2015

1. Two female and two male patients with essential hypertension were given dihydralazine plus saline or dihydralazine plus diclofenac intravenously on two separate occasions. The dihydralazine dose (range: 16.2–32.4 mg/2 h) was chosen individually to reduce systolic blood pressure by 20 mmHg from the control value before the investigation; the intravenous diclofenac dose was 75 mg/20 ml of saline for all patients.

2. Dihydralazine decreased diastolic blood pressure more than systolic blood pressure and increased heart rate; diclofenac reduced both of these effects.

3. Dihydralazine increased urinary volume and sodium clearance; both these effects were antagonized by concomitant treatment with diclofenac.

4. Whereas dihydralazine did not influence creatinine clearance appreciably, concomitant administration of diclofenac reduced creatinine clearance.

5. Urinary prostaglandin E2 was reduced by diclofenac.

6. We suggest that dihydralazine-mediated vasodilatation is reduced by cyclo-oxygenase inhibition.
Effects of Bromocriptine on Blood Pressure and Plasma β-Endorphin in Spontaneously Hypertensive Rats
Authors: Hutchinson J. S. , Di Nicolantonio R. , Lim A. , Clements J. , Funder J. W.
Published: August 2015

1. Immunoreactive β-endorphin (IR-βEP) was two- to three-fold higher in pituitary neuro-intermediate lobes (N-IL) of spontaneously hypertensive rats (SHR) than of normotensive Wistar—Kyoto (NT-WKY) controls.

2. Plasma levels of IR-βEP were lower in SHR than in NT-WKY rats.

3. Intravenous injections of morphine lowered blood pressure of both SHR and NT-WKY rats to the same level; naloxone restored blood pressure of both groups to pre-morphine values.

4. Infusion of bromocriptine in SHR for 1 week lowered blood pressure and N-IL IR-βEP concentration.

5. These results confirm and extend postulated dopaminergic defect in this model of hypertension.
Experimental Essential Hypertension in the Rat?
Authors: Nowaczynski M. , Nowaczynski W. , Mavoungou D. , Wilkins G. , Fung K. , Boyko R.
Published: August 2015

1. A human urinary thermostable glycoprotein (ABG-TsU) believed to be a homologue of the plasma aldosterone-binding globulin (ABG) was isolated and purified by differential ultra-filtration, ion-exchange chromatography and gel filtration to electrophoretic homogeneity; it showed a charge heterogeneity in electrofocussing.

2. ABG-TsU was administered intraperitoneally to male rats in small daily doses (7 μg/day per rat). Sustained hypertension developed in 5–8 days.

3. The treated rats showed no changes in plasma electrolytes, aldosterone or plasma renin activity; however, a significant increase in heart weight was observed.

4. This hypertension appears to be adrenal dependent since it is prevented by bilateral adrenalectomy or administration of an aldosterone antagonist, but not by adrenalectomy when aldosterone is given concomitantly with ABG-TsU.
HLA Antigens in Spanish Patients with Essential Hypertension
Authors: Fernandez-Cruz A. , Otero M. Luque , Perez L. Llorente , Pinilla C. Fernandez , Claros N. Martell
Published: August 2015

1. Human leucocyte AB antigens were determined by means of a lymphocyte toxicity test in 84 patients with essential hypertension and in 1000 blood donors.

2. The prevalence of HLA B8 was 16.4% in hypertensive patients and 8.9% in controls (P = 0.07).

3. The prevalence of HLA B12 was 34.5% in hypertensive patients and 26.9% in the control group (N.S.). In WHO stage III hypertension HLA B12 was found in six out of 10 patients.

4. The prevalence of HLA B15 was 1.2% in hypertensive patients and 6.4% in controls (P < 0.05).

5. In view of a previous report of HLA antigens in a Spanish diabetic population, this study does not support the suggestion of a genetic and possibly HLA-linked connection between essential hypertension and diabetes mellitus among the Spanish population.

6. A positive family history of hypertension tended to be more common in those patients with essential hypertension associated with HLA B8.
Alcohol: Effect on Blood Pressure and Predisposition to Hypertension
Authors: Arkwright P. D. , Beilin L. J. , Rouse I. , Armstrong B. K. , Vandongen R.
Published: August 2015

1. The association between alcohol consumption and blood pressure was studied in 491 Government employees. The men, aged 21–45 years, volunteered to complete a health questionnaire and submitted to standardized measurements of blood pressure, heart rate and body size.

2. Average weekly alcohol consumption correlated with systolic pressure (r = 0.18, P < 0.001) but not with diastolic pressure. Systolic pressure increased progressively with increasing alcohol consumption with no obvious threshold effect. The effect of alcohol was independent of age, obesity (Quetelet's index) or cigarette smoking.

3. Results indicate that alcohol ranks close to obesity as a preventable cause of essential hypertension in the community.
Accuracy of the London School of Hygiene and Remler M2000 sphygmomanometers
Authors: Fitzgerald D. J. , O'Callaghan W. G. , O'Malley K. , O'Brien E. T.
Published: August 2015

1. The accuracy of the Remler M2000, a semiautomatic portable blood pressure recorder, was assessed with the London School of Hygiene (LSH) and Hawkesley random-zero sphygmomanometers used as reference standards.

2. The Remler gave higher recordings than the LSH sphygmomanometer, the mean systolic and diastolic differences being 5.9 mmHg (P < 0.001) and 4.7 mmHg (P < 0.001) respectively. No significant difference was demonstrated between paired Remler and Hawkesley recordings.

3. When simultaneous paired LSH and Hawkesley sphygmomanometer recordings were compared, the LSH gave lower blood pressures: 7.1 mmHg (P < 0.001) for systolic and 3.6 mmHg (P < 0.001) for diastolic recordings.

4. The LSH sphygmomanometer underestimates blood pressure, partly due to a calibration error but also because the selection of end points for this device differs from other methods of blood pressure measurement.
Haemodynamic Effects of Withdrawal of Long-Term Treatment with β-Adrenoceptor Blocking Agents in Subjects with Essential Hypertension
Authors: Bengtsson C. , Larsson Y. , Panfilov V. , Sivertsson R. , Åström H.
Published: August 2015

1. After 10 years of β-adrenoceptor blockade in five female patients with essential hypertension, the β-adrenoceptor-blocking agent was withdrawn, and the women were then followed up for 1 year, with measurements of cardiac output and peripheral resistance.

2. Blood pressure remained low during the first year after withdrawal in spite of the fact that the heart rate increased within the first few days.

3. Cardiac output was found to increase during the first year after withdrawal, although total peripheral resistance was essentially unchanged.

4. The maintenance of low blood pressure after withdrawal of the antihypertensive drug might indicate a regression of structural changes in the resistance vessels during successful long-term antihypertensive treatment.

5. Minimal resistance in hands and calves did not increase during the year after withdrawal.
Effects of Short-Term and Long-Term Treatment with Cardio-Selective and non-Selective β-Receptor Blockade on Carbohydrate and Lipid Metabolism and on Plasma Catecholamines at Rest and during Exercise
Authors: Koch G. , Franz I.-W. , Lohmann F. W.
Published: August 2015

1. The effects on glucose and lipid metabolism and on plasma catecholamines at rest and during exercise, of 4 weeks treatment with non-selective β-blockade (pindolol, 15 mg daily) and with cardio-selective blockade (metoprolol, 200 mg, and acebutolol, 500 mg, respectively) were compared in different groups of hypertensive men (mean age 37 years) by single blind cross-over technique. All patients continued the treatment with either metoprolol or acebutolol for another 12–14 months.

2. All antagonists reduced blood pressures and exercise heart rates in a virtually identical manner. Whereas lipolysis was similarly inhibited by both selective β1-antagonists and non-selective β1-β2-blockers, glycogenolysis in the muscle was inhibited only by non-selective β-receptor blockade.

3. The inhibition of glycogen breakdown resulted in exercise hypoglycaemia and in increases of plasma adrenaline and ACTH, which probably reflect counter-regulatory mechanisms. No major metabolic changes occurred after 12–14 months compared with 4 weeks of treatment.
Decrease in α-Adrenoceptor-Mediated Vasoconstriction Parallels the Antihypertensive Response to Propranolol in Patients with Normal Renin Essential Hypertension
Authors: Amann F. W. , Bolli P. , Hulthén L. , Kiowski W. , Bühler F. R.
Published: August 2015

1. α1-Adrenoceptor-mediated vasoconstriction was studied before and during propranolol therapy in eight normal renin essential hypertensive patients; four were known ‘responders’ and four, age-matched ‘non-responders’ to previous β-receptor blocker monotherapy. Plasma renin activity, plasma adrenaline and noradrenaline concentrations as well as forearm blood flow were measured before and during regional postjunctional α1-adrenoceptor blockade with prazosin. All measurements were done on placebo and again after 6 weeks’ propranolol monotherapy (320 mg/day).

2. Propranolol reduced heart rate and plasma renin activity to the same extent in ‘responders’ and ‘non-responders’. Resting plasma adrenaline concentrations tended to be higher in ‘responders’ before propranolol; they remained unchanged in both groups on propranolol. Plasma noradrenaline concentrations were similar in both groups before and on propranolol.

3. Before propranolol forearm flow was not different in ‘responders’ and ‘non-responders’. Non-specific vasodilatation with sodium nitroprusside produced a similar increase in forearm flow before and after propranolol in both groups.

4. Prazosin-induced increments in forearm flow tended to be higher in ‘responders’ before propranolol. After propranolol the vasodilator effect of prazosin was attenuated in ‘responders’ but it remained unchanged in ‘non-responders’ (P < 0.01).

5. In patients with normal renin essential hypertension the antihypertensive response to propranolol monotherapy is paralleled by a decrease in postjunctional α1-adrenoceptor-mediated vasoconstriction.
Effects of Prizidilol (SKF 92657) on Blood Pressure, Haemodynamics, Sympathetic Nervous System Activity and Plasma Volume in Essential Hypertension
Authors: Fariello R. , Alicandri C. L. , Agabiti-Rosei E. , Romanelli G. , Castellano M. , Beschi Marina , Platto Letizia , Di Priolo Susanna Leto , Muiesan G.
Published: August 2015

1. The antihypertensive effect of 4 weeks' treatment with prizidilol (SKF 92657) (mean dosage 520 mg once or twice daily) was studied in ten essential hypertensive patients.

2. Both systolic and diastolic blood pressure were significantly reduced in all cases. Supine heart rate did not change, and in the erect position heart rate was significantly lowered.

3. Blood pressure reduction was due to peripheral vasodilatation, as the cardiac index increased after 4 weeks of prizidilol treatment.

4. After prizidilol plasma noradrenaline and adrenaline increased significantly, and PRA and plasma aldosterone were reduced. Although plasma volume increased, body weight did not change.

5. Cardiac performance, as evaluated by the PEP/LVET ratio, improved after treatment with prizidilol.
Role of Prostaglandins in Mediating Excretion by the Kidney of an Intravenous Infusion of Sodium Chloride in Normal Human Subjects
Authors: Watson M. L. , Lambie A. T. , Thom A. , Ungar A.
Published: August 2015

1. Normal male subjects were given a rapid infusion of 3 litres of sodium chloride solution (150 mmol/l) with or without pretreatment with indomethacin.

2. There was marked individual variability in the rate at which the infused sodium chloride solution was subsequently excreted which was not related to the urinary sodium excretion in the previous 24 h.

3. There was no relationship between urinary prostaglandin E excretion during the 24 h preceding the sodium chloride infusion and the rate at which different individuals subsequently excreted sodium and water.

4. Renal plasma flow was significantly higher during the sodium chloride infusion than in the post-infusion recovery period, both with and without pretreatment with indomethacin, although it was significantly lower during each period in subjects pretreated with indomethacin.

5. Urinary prostaglandin E excretion was significantly decreased after the infusion of sodium chloride solution.

6. Indomethacin slightly decreased the rate of excretion of sodium and water.

7. Prostaglandins have a role in, but are not the main determinants of, the excretion of an intravenous infusion of sodium chloride.

8. The results do not support the suggestion that prostaglandin E produced within the kidney, as indicated by urinary prostaglandin E excretion, exerts a natriuretic action.
Pathogenesis of Salt Retention in Dogs with Chronic Bile-Duct Ligation
Authors: Chaimovitz C. , Alon U. , Better O. S.
Published: August 2015

1. The present study investigates the role of mineralocorticoids in the pathogenesis of salt retention and ascites in dogs with chronic ligation of the common bile duct (CBDL).

2. After CBDL the natriuretic response to an intravenous sodium load [0.9% sodium chloride solution (150 mmol/l): saline; 10% of body weight] was markedly depressed. Urinary sodium excretion was 285 ± 62 vs 960 ± 58 μmol/min in the control period before CBDL (P < 0.001). This antinatriuresis was associated with a significant rise in plasma aldosterone concentration, from 52.5 ± 5.5 pg/ml before CBDL to 177 ± 50 pg/ml after CBDL (P < 0.02). Ascites was present in all salt-retaining CBDL dogs.

3. Bilateral adrenalectomy resulted in disappearance of ascites and in a rise in the natriuretic response to extracellular volume expansion. Urinary sodium excretion was 770 ± 124 μmol/min, a value significantly higher than in the CBDL dogs with intact adrenals (P < 0.001). Sodium balance studies in the adrenalectomized CBDL dogs during chronic deoxycorticosterone acetate (DOCA) treatment (25 mg/day) showed that in these animals there was failure to escape from the mineralocorticoid-induced sodium retention. Glomerular filtration rate and renal plasma flow did not change during the studies.

4. The present evidence supports the thesis that sodium retention in the CBDL dog results from a dual mechanism: (a) excess of circulating aldosterone and (b) an extra-adrenal factor which prevents escape from the salt-retaining effect of mineralocorticoids, in the CBDL dogs, thereby perpetuating the antinatriuresis in these animals.
Intracellular Free Amino Acids in Undernourished Patients with or without Sepsis
Authors: Milewski P. J. , Threlfall C. J. , Heath D. F. , Holbrook I. B. , Wilford K. , Irving M. H.
Published: August 2015

1. Thigh muscle samples for analysis were obtained from 35 control subjects and 12 severely ill patients, of whom five had disease-induced undernutrition and seven had associated sepsis. An improvement in the Bergström technique for analysing muscle needle biopsy samples was used.

2. Muscle water, chloride and DNA were increased in both groups of ill patients, indicating an increase in the extracellular component and loss of muscle protein.

3. Falls in the concentrations of glutamine, glutamate, arginine, histidine, ornithine and lysine and rises in those of glycine, serine, asparagine, tyrosine, valine, leucine, isoleucine, phenylalanine, methionine and tryptophan were observed in the group of ill patients compared with those in the control subjects. The changes were present mainly in the patients with sepsis, significant differences between these and the undernourished ones without associated sepsis being observed in glutamine, lysine, tyrosine, valine, leucine, isoleucine, phenylalanine and methionine. The changes were either absent or slight in plasma.

4. The increased concentrations observed in six essential amino acids in the septic patients, but not in those with undernutrition, is consistent with the increased catabolic rate of sepsis.

5. However, the branched-chain amino acids, and lysine, threonine, arginine, and histidine, were present in lower concentrations than might be expected from catabolism, presumably due to utilization. It is suggested therefore that septic patients might benefit from increased proportions of these amino acids in their feeding regimen.
Studies of a Variant Very-Low-Density Lipoprotein with an Acquired Deficiency of Apolipoprotein C-II
Authors: Reckless J. P. D. , Stocks J. , Holdsworth G. , Galton D. J. , Suggett A. J. , Walton K. W.
Published: August 2015

1. A variant very-low-density lipoprotein was associated with severe hypertriglyceridaemia. Urea—polyacrylamide gel electrophoresis of the tetramethylurea-soluble apolipoproteins of these very-low-density lipoproteins (VLDL) showed that the apolipoprotein C-II content was less than 10% of that in VLDL from hypertriglyceridaemic (3–120 mmol/l) controls.

2. VLDL were incubated with bovine milk lipoprotein lipase (LPL) and a 9,10-3H-labelled triglyceride emulsion. The VLDL deficient in apolipoprotein C-II were a poor activator of LPL, compared with the effect of VLDL with normal content of apolipoprotein C-II obtained from either normal or hypertriglyceridaemic sera.

3. The efficacies of various VLDL as substrates for activated LPL were examined. Apolipoprotein C-II-deficient VLDL were a poor substrate for the activated enzyme compared with normal or hypertriglyceridaemic VLDL, and compared with an artificial triglyceride emulsion.

4. The abnormal VLDL were obtained from a subject with an IgG3 lambda myeloma protein. Intravenous infusion of normal plasma containing apolipoprotein C-II was followed by rapid, complete, but short-lived (5–10 days) clearance of serum triglyceride. The effect was observed on three occasions until treatment of the myeloma was effective.

5. The monoclonal protein behaved as a cryoglobulin, and formed large particle complexes with triglyceride-rich lipoproteins, especially at temperatures below 37°C. The apolipoprotein C-II deficiency, and consequent hypertriglyceridaemia, may be secondary to an autoantibody directed against apolipoprotein C-II. VLDL from relatives with hypertriglyceridaemia, but without myeloma, had normal apolipoprotein content, activated LPL, and were efficient substrates for the enzyme.
Effect of Acute Vasopressin Infusion on Blood Pressure and Plasma Angiotensin II in Normotensive and DOC A—Salt Hypertensive Rats
Authors: Morton J. J. , Del Rio C. Garcia , Hughes Maria J.
Published: August 2015

1. Arginine vasopressin was infused at 0.5, 2, 6, 18 or 54 ng min−1 kg−1 for 1 h into normal, sham-operated and DOCA—salt hypertensive rats. Complete vasopressin/blood pressure dose—response curves were constructed from circulating plasma vasopressin concentrations measured at the end of each infusion.

2. DOCA—salt hypertensive rats had a higher basal plasma vasopressin concentration (11.1 ± sd 3.7 fmol/ml) than either the normal (3.9 ± 2.3, P < 0.01) or the sham-operated rats (4.5 ± 2.4, P < 0.01).

3. The DOCA—salt hypertensive rats did not have any detectable enhancement of pressor sensitivity, compared with either of the two normotensive groups.

4. There was no significant increase in blood pressure in either the normal rats or sham-operated rats until vasopressin was infused at 2 ng min−1 kg−1, when the plasma concentration was between 30 and 40 fmol/ml.

5. Subpressor infusion of vasopressin in the normal and sham-operated rats, which gave plasma concentrations of 22–23 fmol/ml, completely suppressed plasma angiotensin II to levels similar to the basal values found in the DOCA—salt hypertensive rats (10.5 ± 2.3, 14.5 ± 4.5 and 8.0 ± 1.6 fmol/ml respectively).

6. These findings suggest that the mechanism of vasopressin involvement in DOCA—salt hypertension is as yet unclear, that short-term changes in vasopressin concentration appear unimportant in the regulation of normal blood pressure, that small physiological changes of vasopressin in normal rats may be important in the regulation of renin secretion, and that the increase in vasopressin concentration seen in DOCA—salt hypertension may contribute to the suppression of renin and angiotensin II in this state.
Glutamine Production Rate and its Contribution to Urinary Ammonia in Normal Man
Authors: Golden M. H. N. , Jahoor P. , Jackson A. A.
Published: August 2015

1. Glutamine [15N]amide was infused at a steady rate of 33.34 μmol/h into seven male adult volunteers who were in the fed state and normal acid-base status.

2. Plasma glutamine amide N enrichment and urinary ammonia N enrichment rose to a constant value within 3 h.

3. The glutamine production rate was 51.8 ± 7.9 mmol/h.

4. The total ammonia excretion rate was 0.87 mmol/h. Of this excreted ammonia 62.6 ± 9% was derived from the amide N atom of glutamine.

5. The excreted glutamine amide N (0.53 mmol/h) was only 1% of the glutamine production. If half the ammonia formed by the kidney is excreted in urine and half liberated into the renal vein in subjects with normal acid-base status [E. E. Owen & R. R. Robinson (1963) Journal of Clinical Investigation, 42, 263–276], then the kidney accounts for only 2% of glutamine disposal.

6. Whole body protein turnover, measured from the urinary [15N]ammonia enrichment, was 30.3 ± 7.7 g of N/day (2.8 g of protein day−1 kg−1).
Baroreceptor Stimulation and Isometric Exercise in Normotensive and Borderline Hypertensive Subjects
Authors: Suarez D. H. , Messerli F. H. , Ventura H. O. , Aristimuno G. , Dreslinski G. R. , Frohlich E. D.
Published: August 2015

1. The effects of carotid baroreceptor stimulation (neck chamber) on systemic haemodynamics were determined for normotensive and borderline hypertensive subjects during periods of resting and isometric exercise.

2. Both groups reacted to baroreceptor stimulation with a similar decrease in mean arterial pressure and cardiac index at rest and during isometric exercise, but baseline heart rate decreased more in borderline hypertensive patients.

3. Baroreceptor stimulation elicited the same haemodynamic response at rest and during exercise-induced arterial pressure increase. Since the magnitude of arterial pressure had no bearing on the subsequent response, these data suggest resetting of baroreceptors during this short-term blood pressure increase.
Multiple Molecular Forms of Human Heart Cytoplasmic Aspartate Aminotransferase
Authors: Leung F. Y. , Henderson A. R.
Published: August 2015

1. Cytoplasmic aspartate aminotransferase was isolated and purified from human heart with a final specific activity of 236 units/mg of protein.

2. Three distinct peaks of aspartate aminotransferase activity were detected by isoelectric focusing with isoelectric points of 5.46, 5.60 and 5.71. Two minor subforms were also noted as shoulder patterns with pI 5.2 and 5.8.

3. These electrophoretic characteristics are similar to previous findings of multiple molecular forms detected in human liver and erythrocytes.
Heritability of the Low Density Lipoprotein Receptor Activity of Human Blood Mononuclear Cells: Studies in Normolipidaemic Adult Male Twins
Authors: Weight M. , Cortese C. , Miller U. Sule N. E. , Lewis B.
Published: August 2015

1. The concordance of low density lipoprotein (LDL) receptor activity of blood mononuclear cells was examined in 26 pairs of monozygotic and 17 pairs of dizygotic normolipidaemic young adult male twins.

2. Receptor activity was quantified as the degradation of 125I-labelled LDL during a 6 h incubation, after derepression of the cells for 72 h in lipoprotein-deficient medium.

3. The total variance of receptor activity was similar in the two groups of twins. In contrast, within-pair variance was five times greater in dizygotic twins than in monozygotic twins (P < 0.001).

4. Estimates of heritability, mostly based on the intra-class correlation coefficients (monozygotic, r = 0.83; dizygotic, r = 0.39), ranged from 0.72 to 1.05.

5. These results suggest that the maximal LDL receptor activity of peripheral cells in normolipidaemic subjects is largely genetically determined.
Urate Does Not Influence the Formation of Calcium Oxalate Crystals in Whole Human Urine at pH 5·3
Authors: Hallson P. C. , Rose G. A. , Sulaiman S.
Published: August 2015

1. Samples of fresh human urine were treated with immobilized uricase to lower urate concentration. Urate was added to yield low, normal and high urate samples.

2. Each sample was rapidly evaporated at pH 5.3 to standard osmolality and the yield of calcium oxalate crystals measured either by semi-quantitative microscopy or fully quantitative radioisotope techniques.

3. Increase of urinary urate did not increase the calcium oxalate crystals formed and may even have had an opposite effect.

4. Allantoin was without significant effect upon calcium oxalate crystal formation.

5. These data provide no support for the suggestion that reducing urate concentrations in the urine may be of value in treatment of patients with calcium oxalate stones.
Absence of Activation in Vitro of Renin in Rat Plasma
Authors: De Keijzer M. H. , Provoost A. P. , Derkx F. H. M.
Published: August 2015

1. Rat plasma was subjected at 4°C to various treatments known to convert inactive renin into its active form in human plasma.

2. No statistical differences in plasma renin concentration were found when the levels after the various treatments were compared with that of untreated rat plasma.

3. It is concluded that, in contrast to human plasma, no inactive form of renin is present in rat plasma.
The Renin-Angiotensin-Aldosterone System, Antidiuretic Hormone and Sympathetic Nerve Activity in an Experimental Model of Congestive Heart Failure in the Dog
Authors: Riegger A. J. G. , Liebau G.
Published: August 2015

1. Congestive heart failure was induced in dogs by rapid pacemaker stimulation of the heart (240–280/min) for 14 days. This represents a model of low output heart failure which permits the study of the development and reversal of congestive heart failure in an anatomically intact circulation in the unanaesthetized animal.

2. Cardiac output was reduced by 54%. Pulmonary artery pressure gradually increased by a facter of 2.4 and pulmonary capillary pressure rose to 4.6 times basal values. The animals retained a mean of 1.1 litres of fluid.

3. At the same time there was a gradual increase of plasma levels of renin, angiotension II, aldosterone, noradrenaline and adrenaline. After the pacemaker stimulation was discontinued all hormone levels returned to normal, the retained fluid was excreted, and intracardiac pressures and cardiac output returned to baseline values.

4. When heart failure was established at the end of the pacemaker stimulation period an inappropriately high secretion of antidiuretic hormone in relation to plasma osmolality was observed in five of six dogs.

5. It is concluded that beside the well-known non-hormonal renal factors, these hormone systems-5-be involved in the formation of oedema in congestive heart failure. The inappropriately high levels of antidiuretic hormone-5-cause hyponatraemia by water retention, representing a state of ‘dilutional hypo-osmolality’.