bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasopressin Blood Pressure Dependency after α-Adrenoceptor Blockade in Normotensive and Mineralocorticoid-Salt Hypertensive Rats
Authors: Burnier M. , Biollaz J. , Brunner H. R. , Gavras H.
Published: August 2015

1. The effect of α-adrenoceptor blockade by phentolamine on plasma arginine vasopressin, on vasopressin dependency of blood pressure and on responsiveness to exogenous lysine vasopressin was studied in conscious normotensive and in deoxycorticosterone (DOC)/salt-treated hypertensive rats.

2. Phentolamine infusion reduced blood pressure of DOC-treated hypertensive rats to levels significantly lower than those of similarly treated Wistar control animals.

3. Plasma vasopressin levels of the DOC-treated hypertensive and normotensive control rats were similar. Phentolamine infusion increased plasma arginine vasopressin levels to 109.4 ±21.8 pg/ml in the DOC-treated rats and to 44.4 ± 8.2 pg/ml in the control animals. It also enhanced the pressor response to exogenous lysine vasopressin in both groups.

4. Administration of the vasopressin analogue dPVDAVP had no effect on blood pressure in either the DOC-treated or the control group but induced a similar fall in blood pressure in both groups during α-adrenoceptor blockade with phentolamine.
Biosynthetic Enzyme Activities and Catecholamines in Adrenal Glands of Genetic and Experimental Hypertensive Rats
Authors: Grobecker Horst , Saavedra Juan , Weise Virginia
Published: August 2015

1. There was a significant decrease in the activity of tryosine hydroxylase, dopamine-β-hydroxylase and phenylethanolamine-N-methyltransferase in young spontaneously hypertensive rats (SHR) at the age of 2 and 4 weeks, compared with the activity in adrenals of the Wistar-Kyoto rat substrain. Tyrosine hydroxylase activity was not different in normotensive and hypertensive animals at 8 weeks of age but was increased in adult SHR.

2. Both dopamine-β-hydroxylase and phenylethanolamine-N-methyltransferase activities were still decreased at the age of 8 weeks in SHR, but were not significantly different from the controls at the age of 14 weeks. Blood pressures in SHR were slightly but significantly higher at 4 weeks of age and steadily rose during maturation.

3. In DOCA-saline hypertensive rats, tyrosine hydroxylase activity in adrenals was increased after only 1 week of treatment and remained increased after 2 and 4 weeks of treatment. Adrenal adrenaline was increased after 4 weeks of treatment, whereas dopamine-β-hydroxylase and phenylethanolamine-N-methyltransferase activities and noradrenaline levels were unchanged.

4. Our findings of increased tyrosine hydroxylase in adrenal glands of adult genetically hypertensive and chronic experimentally hypertensive rats indicate a sympathoadrenal activation during the established phase of the hypertension in both models. Whereas in DOCA-saline hypertensive rats catecholamine synthesis in adrenals parallels the development of high blood pressure, in genetically hypertensive rats the activity of the catecholamine-synthesizing enzymes is decreased early in development. These results suggest the existence of different mechanisms regulating the participation of adrenal catecholamines in both models of experimental hypertension.
Purification and Properties of Bovine Pituitary Renin
Authors: Ohsawa Tamiko , Hirose Shigehisa , Inagami Tadashi , Murakami Kazuo
Published: August 2015

1. Renin was purified to homogeneity from bovine anterior pituitary by using batchwise DEAE-cellulose chromatography, pepstatin-aminohexyl-agarose affinity chromatography, Ultrogel AcA 44 gel filtration and DEAE-Sephacel and CM-cellulose ion exchange chromatography.

2. The enzyme has a molecular weight of 36 000 and an isoelectric point of 5.25, and exhibits optimum activity at a pH between 6.5 and 7.5.

3. The amino acid composition and antigenic properties of this purified renin are very similar to those of rat, dog and hog kidney renins.
Effect of a High Linoleic Acid Diet and Thiazide on Sodium Chloride-Induced Hypertension in Rats
Authors: Tobian Louis , Johnson Mary Ann , Ganguli Mukul , Lange Judith , Kartheiser Karen , Iwai Junichi
Published: August 2015

1. Hypertension-prone Dahl S rats on either low or high NaCl diets have less than half the concentration of prostaglandin E2 (PGE2) in quick-frozen renal papillae compared with that of hypertension-resistant Dahl R rats.

2. A 4% high NaCl diet doubles the concentration of PGE2 in the renal papillae compared with the effect of a moderately low (0.3%) NaCl diet.

3. A diet with 16% linoleic acid triples the PGE2 concentration in S papillae and increases it 2.5 times in R papillae, compared with a diet with 1.5% linoleic acid.

4. The 16% linoleic acid diet also delays the onset of NaCl-induced hypertension and prevents about half of the ultimate rise in blood pressure.

5. The low PGE2 concentration in the renal papillae of S rats could contribute to a tendency toward sodium retention and thereby encourage NaCl-induced hypertension.

6. Thiazides greatly increase sodium and water excretion in isolated kidneys from pre-hypertensive S rats perfused with blood at a normotensive arterial inflow pressure. This effect would allow brisk natriuresis without the need for hypertensive arterial pressures and could thereby reduce blood pressure in NaCl-related hypertension.
Renal and Vascular Wall Prostaglandins in Spontaneously Hypertensive Rats
Authors: Ozawa Yukio , Kan Keika , Konishi Konosuke , Kitajima Waichi , Matsumura Yasuo
Published: August 2015

1. Renal cortical and medullary tissue and aortic wall were removed from spontaneously hypertensive rats and from age-matched Wistar-Kyoto control animals at ages 30, 60, 90 and 120 days. The tissues were incubated and the release of prostaglandins into the incubation medium was measured.

2. Compared with Wistar-Kyoto control animals, the release of prostaglandin E from renal medullary tissue in spontaneously hypertensive rats was raised at 30 days (pre-hypertensive stage) and 90 days (early hypertensive stage), but decreased later with further establishment of hypertension. No such trend was seen with renal cortical tissue. Tissue release of prostaglandin F tended to be generally high in the spontaneously hypertensive rats compared with that in the control animals, but the difference was not significant.

3. The release of prostaglandin I2, as indicated by measurements of 6-keto prostaglandin F1α, from aortic wall tissue in the spontaneously hypertensive rat during its pre-hypertensive and early hypertensive stages was similar to values obtained in the age-matched control animal. However, aortic wall prostaglandin I2 release in spontaneously hypertensive rats increased thereafter, and was significantly raised at 90 and 120 days. No similar trend was observed with thromboxan A2 release. Release of prostaglandin I2 and thromboxan A2 from renal tissues in spontaneously hypertensive rats did not differ significantly from that in control animals.

4. It is suggested that indomethacin-induced aggravation of hypertension in the spontaneously hypertensive rat may result from suppression of aortic wall prostaglandin I2 formation rather than from the suppression of renal prostaglandin E2 production.
Does β-Endorphin Contribute to the Central Antihypertensive Action of α-Methyldopa in Rats?
Authors: Petty M. A. , De Jong W.
Published: August 2015

1. Opioid peptide involvement in the fall in blood pressure resulting from central α-receptor stimulation has been investigated.

2. In conscious renal hypertensive rats (two-kidney, one clip Goldblatt model), α-methyldopa (100 mg/kg intraperitoneally) produced a long-lasting fall in blood pressure which was partially attenuated by pre-treatment with naltrexone (5 mg/kg subcutaneously).

3. Unilateral injection of α-methylnoradrenaline (50 nmol) into the nucleus tractus solitarii of normotensive, urethane-anaesthetized rats induced a fall in blood pressure and heart rate. This fall was prevented by pretreatment with naloxone, either 1 mg/kg subcutaneously or 1 and 10 ng administered directly into the nucleus.

4. Pretreatment with antiserum to β-endorphin (1:50 dilution), applied locally, also blocked the depressor response induced by the catecholamine.

5. These results suggest that the fall in blood pressure observed after α-methyldopa and its active metabolite α-methylnoradrenaline involves a β-endorphin-like peptide; a possible site of action is the nucleus tractus solitarii.
Effect of Sympathetic Nerve Inhibition on the State of Sodium—Volume Balance in Hypertensive Patients with Normal or Impaired Renal Function
Authors: Campes V. M. , Levitan D. , Romoff M. S. , Saglikes Y. , Sajo I. , Massry S. G.
Published: August 2015

1. The effect of clonidine on the relationship between sympathetic nervous system activity and the state of sodium-volume balance was studied in 15 patients with essential hypertension and normal renal function (group 1) and in 14 patients with hypertension and mild to moderate renal failure (group 2).

2. Acutely, clonidine (200 μg) produced significant falls (P < 0.01) in mean blood pressure, plasma noradrenaline, plasma renin activity and plasma aldosterone in both groups of patients. The changes in mean blood pressure were significantly correlated (P < 0.01) with the changes in plasma noradrenaline.

3. Chronic therapy with clonidine also produced significant falls in mean blood pressure and plasma noradrenaline, but not in plasma renin activity or aldosterone.

4. Exchangeable sodium and plasma volume decreased significantly in patients of group 1 but not in patients of group 2.

5. The data indicate that sympathetic nerve activity may be important for the abnormal relationship between pressure and natriuresis in subjects with essential hypertension and normal renal function, but not in hypertensive subjects with impaired renal function.
Sodium-Accelerated Platelet Aggregation in Men Predisposed to Essential Hypertension
Authors: Nara Y. , Kihara M. , Kanbe T. , Horie R. , Endo J. , Yamori Y.
Published: August 2015

1. Men with a genetic predisposition to essential hypertension had a significantly higher blood pressure during salt restriction and a greater elevation of blood pressure in response to salt loading than men without such a genetic predisposition.

2. The activity of platelet aggregation was significantly greater in men with a genetic predisposition to essential hypertension.

3. Platelet aggregation was activated directly or indirectly by an increased sodium intake.

4. This activation by an increased sodium intake was more pronounced in men predisposed to essential hypertension.
Effects of Clonidine and Hydrochlorothiazide on the Cardiovascular Response to Mental Stress in Adolescent Hypertension
Authors: Falkner Bonita , Onesti Gaddo , Affrime Melton B. , Lowenthal David T.
Published: August 2015

1. The effects of clonidine and hydrochlorothiazide on the cardiovascular responses to mental stess were compared in 29 adolescents with essential hypertension.

2. Clonidine therapy was associated with lower diastolic pressures, heart rate and noradrenaline in response to mental stress. By contrast, hydrochlorothiazide resulted in the reduction of systolic pressure only. The mental stress testing produced a greater absolute diastolic pressure response and higher plasma noradrenaline on hydrochlorothiazide therapy.

3. Juveniles with essential hypertension may be more sensitive to central control of blood pressure and more resistant to diuretics.

4. The reduced diastolic pressure and heart rate response to central stimuli during clonidine therapy may be related to decreased adrenergic activity, as indicated by lower plasma noradrenaline.
The Pulmonary Haemodynamic Effects of Almitrine Infusion in Men with Chronic Hypercapnia
Authors: Dull W. L. , Polu J. M. , Sadoul P.
Published: August 2015

1. Almitrine, an agonist of peripheral chemoreceptors, has been shown to be effective in lowering Paco2 in patients with chronic obstructive lung disease. The aim of this investigation was to evaluate the pulmonary haemodynamic response to almitrine in clinically stable patients with chronic airflow obstruction and chronic hypercapnia (Paco2 7.1 ± 0.5 kPa, mean ± sd).

2. Seven men, aged from 55 to 64 years, had the following values for pulmonary function (means ± sd): FEV1.0 0.67 ± 0.16 litre; VC 2.12 ± 0.52 litres; FEV1.0/VC 33 ± 8%. They had haemodynamic monitoring during 1 h of almitrine (1 mg/kg intravenously) and solvent (placebo) in a random fashion while receiving 28% oxygen. Before infusion, six patients had evidence of pulmonary hypertension and the mean pulmonary artery pressure (PAP) for all seven patients was 4.3 ± 1.6 kPa (mean ± sd); the pulmonary vascular resistance (PVR) was 0.61 ± 0.22 kPa l−1 s (mean ± sd).

3. There were no significant changes from baseline values during placebo. During almitrine, however, the PAP and right ventricular stroke work (mean ± sd) increased significantly at 30 min (6.0 ± 2.1 kPa, P < 0.001, 0.38 ± 0.12 J, P < 0.05, respectively) with maximum increase of PVR at 45 min (1.01 ± 0.34 kPa l−1 s, P < 0.001, mean ± sd). The lowest Paco2 (mean ± sd) was observed at the end of the infusion (5.7 ± 0.5 kPa, P < 0.001).

4. These results confirm the benefit of almitrine in lowering Paco2 in patients with chronic airflow obstruction who have chronic hypercapnia but also demonstrate significant pulmonary vasoconstriction.
Factors Influencing the Regional Deposition of Inhaled Particles in Man
Authors: Chamberlain M. J. , Morgan W. K. C. , Vinitski S.
Published: August 2015

1. Although ventilation in normal human lungs has been shown to decrease from apex to base, comparable observations are lacking in regard to particle deposition.

2. We compared regional ventilation and particle deposition in normal subjects by using radioactive xenon and a radioactive aerosol while sitting, lying, and while breathing at an increased rate. Both smokers and non-smokers were studied.

3. Particle deposition and ventilation were closely related, and the greater the ventilation the greater the deposition of particles, a situation which prevailed irrespective of position and breathing rate. While supine, the apex to base gradient for both ventilation and particle deposition decreased but did not entirely disappear. At higher respiratory rates, central deposition of particles, especially in smokers, increased.

4. We concluded that there are regional differences in the deposition of particles and that such differences are closely related to regional ventilation.
A Study on the Distribution of Body Fluids after Rapid Saline Expansion in Normal Subjects and in Patients with Renal Insufficiency: Preferential Intravascular Deposition in Renal Failure
Authors: Koomans Hendrik A. , Geers Anton B. , Boer Peter , Roos Jan C. , Mees Evert J. Dorhout
Published: August 2015

1. The effect of rapid intravenous infusion of 25 ml of isotonic sodium chloride solution (saline)/kg body weight on extracellular fluid volume (ECFV, 82Br distribution volume), plasma volume (131I-labelled albumin distribution volume) and blood volume (from plasma volume and packed cell volume) was studied in nine normal subjects and a group of 11 patients with end-stage renal disease (ESRD).

2. Immediately after the infusion, the increases in ECFV were equal in the two groups but the increases in plasma and blood volumes were significantly larger in the patients with ESRD.

.3. Ninety minutes after the end of the infusion, the blood volume/ECFV ratio was significantly decreased from the control value in the normal subjects, but slightly increased in the patients with ESRD.

4. It is concluded that in severe renal failure the control of fluid distribution is changed in a way which leads to a preferential distribution of rapidly infused saline into the intravascular compartment.
The Interaction of Cigarette Smoke Solution with α1-Antitrypsin: Effect on Inhibitory Capacity, Electrophoretic Mobility and Immunological Measurement
Authors: Stockley Robert A. , Afford Simon C.
Published: August 2015

1. The effects of an aqueous solution of cigarette smoke upon the functional, immunological and electrophoretic assessment of α1-antitrypsin have been studied.

2. The addition of cigarette smoke reduced the inhibitory capacity of the α1-antitrypsin and this was associated with at least a 22% underestimation of the protein concentration by immunological measurement.

3. Furthermore the cigarette-smoke-damaged α1-antitrypsin had an increased electrophoretic mobility in plain agarose compared with the pure protein and was more susceptible to proteolytic damage by elastase.

4. Comparison with results obtained in vivo suggests that oxidative damage to α1-antitrypsin is not the only mechanism involved in the reduction of its inhibitory capacity in secretions, even in non-smokers.
The Role of Cardiopulmonary Sympathetic Afferents in Blood Volume Homoeostasis in the Non-Human Primate
Authors: Cornish Kurtis G. , Gilmore Joseph P.
Published: August 2015

1. Four Macaca fascicularis monkeys were bilaterally sympathectomized by removing the thoracic sympathetic chain from the middle cervical ganglion to the T-6 sympathetic ganglion. This was done chronically, allowing adequate recovery time. While under light pentobarbital anaesthesia, the animals were then subjected to blood volume expansions with isotonic, isooncotic dextran or to head-out immersions. Seven immersions and seven volume expansions were carried out.

2. With immersion, there were significant increases in blood pressure, central venous pressure, urine flow, sodium excretion, potassium excretion, glomerular filtration rate, percentage of filtered sodium excreted and free water clearance. Although blood pressure and central venous pressure initially increased during the first immersion period, heart rate continued to increase with the immersion, while blood pressure and central venous pressure remained constant. Volume expansion caused an increase in central venous pressure, urine flow, sodium and potassium excretion, osmolar clearance, free water clearance, percentage of filtered sodium excreted and glomerular filtration rate.

3. Since these results with both the immersions and volume expansions were not qualitatively different from those observed in control animals, it is concluded that cardiopulmonary sympathetic afferents are not necessary for the renal response to head-out immersion or blood volume expansion in the non-human primate.
Dose-Dependent Effects of Meclofenamate on Peripheral Vasculature of Conscious Rabbits
Authors: Banks R. A. , Beilin L. J. , Soltys J.
Published: August 2015

1. Changes in systemic haemodynamics and organ blood flow were measured in conscious rabbits after various doses of intravenous sodium meclofenamate, an inhibitor of prostaglandin cyclo-oxygenase.

2. Meclofenamate had no effect on arterial pressure or cardiac output but caused a dose-dependent fall in renal blood flow.

3. Meclofenamate also reduced adrenal perfusion but, in contrast, caused a dose-dependent increase in blood flow to the brain, bronchial and hepatic circulation and to the testis. No effect was demonstrated on other organs studied.

4. The effect on the cerebral circulation was observed at the lowest dose of meclofenamate (0.75 mg/kg). Higher total doses were necessary for an effect on the renal and bronchial (3 mg/kg) and testicular and hepatic arteries (6 mg/kg).

5. The results suggest a variety of local vasomotor influences of renal and non-renal prostaglandins in conscious rabbits.
Development of the Respiratory Compensation to Progressive Metabolic Alkalosis Resulting from Potassium Depletion in Conscious Rats
Authors: Girard Pierre , Brun-Pascaud Monique , Pocidalo Jean-Jacques
Published: August 2015

1. 288 arterial blood samples were obtained at successive times, through indwelling catheters, from conscious rats subjected to selective dietary potassium restriction for up to 5 weeks.

2. in control rats with unrestricted access to potassium [HCO−3]a = 25.4 mmol/l, pHa = 7.47, Paco2 = 34 mmHg, Pao2 = 94 mmHg and [K+]a = 4.3 mmol/l were steady and within the range of values reported in conscious rats. Five weeks of isolated potassium restriction resulted in significant hypokalaemia ([K+]a = 2.15 mmol/l) and metabolic alkalosis ([HCO−3]a = 34.1 mmol/l, pH 7.57). This alkalosis, due mostly to H+ transfer into cells, was accompanied by a significant increase in Paco2 to 36.4 mmHg and decrease in Pao2 to 88 mmHg, contrary to previous reports in man and dog. The administration of neutral sodium phosphate in addition to potassium restriction enhanced both the alkalosis ([HCO−3]a = 42.3 mmol/l, pH 7.61) and its respiratory compensation (Paco2 = 40.8, Pao2 = 82 mmHg), without altering the Paco2: [HCO−3]a relationship.

3. The opposite variations of Paco2 and Pao2 were significantly correlated to the increase in plasma bicarbonate concentration and described best by crossed sigmoid curves. The equations of both curves were calculated; their point of inflection occurred at the same bicarbonate concentration (36 mmol/l). The maximum intensity of respiratory compensation (0.62 mmHg Paco2 for each mmol [HCO−3]a/l) observed at this point fell within the range of values yielded by previous estimations.
Do Elderly Patients with An Excessive Fall in Blood Pressure on Standing Have Evidence of Autonomic Failure?
Authors: Robinson Brian J. , Johnson Ralph H. , Lambie David G. , Palmer Karen T.
Published: August 2015

1. Blood pressure, heart rate and plasma catecholamine responses were examined in two groups of elderly subjects distinguished by blood pressure responses to standing. Subjects in the control group showed a fall of less than 15 mmHg in systolic blood pressure on standing; subjects in the orthostatic hypotension group had falls of more than 20 mmHg systolic and 10 mmHg diastolic blood pressure on standing.

2. The heart pressure response on standing showed no significant difference between the two groups.

3. The orthostatic hypotension patients had lower plasma noradrenaline concentrations than the control patients (P < 0.01) in the supine position, but during 10 min standing there was no significant difference in noradrenaline levels between the groups, and the percentage increase of noradrenaline levels in the orthostatic hypotension group was greater (P < 0.05) than in the control group.

4. in the supine position, diastolic blood pressure was higher (P < 0.05) in the orthostatic hypotension group than in the control group.

5. We conclude that impairment of baroreceptor function is not involved in most cases of orthostatic hypotension in the elderly, nor is there reduction of sympathetic nervous activity. We suggest that mechanical changes or adrenoreceptor dysfunction are more likely to be important factors in orthostatic hypotension in the elderly.
Sex-Steroid Enzymes, Aromatase and 5α-Reductase in the Pancreas: A Comparison of Normal Adult, Foetal and Malignant Tissue
Authors: Iqbal M. Jawed , Greenway Brian , Wilkinson M. L. , Johnson P. J. , Williams Roger
Published: August 2015

1. Following the finding of high levels of oestrogen receptor proteins in pancreatic carcinoma tissue, two enzymes involved in sex-steroid biosynthetic pathways, aromatase and 5α-reductase, have been measured.

2. Activities of aromatase, which converts testosterone into oestradiol, comparable with those found in pre-menopausal uterus (P < 0.5) were found in all seven samples of pancreatic carcinoma tissue, and in a pooled sample of foetal pancreas. Measurable but significantly lower activities (P < 0.001) of aromatase were found in seven specimens of normal pancreas.

3. 5α-Reductase activity, which converts testosterone into the more potent androgen 5α-dihydrotestosterone, was found in malignant pancreatic tissue at approximately half the level found in prostatic tissue (P < 0.01) and at almost twice the levels found in either normal adult or pooled foetal pancreatic tissue (P < 0.01).

4. These findings suggest that sex steroids are involved in foetal and adult pancreatic physiology.

5. Since these enzyme pathways are present in pancreatic carcinoma at greater levels than those in normal adult pancreas, it is possible that agents known to interfere with steroid metabolism could be of value in the treatment of this tumour.
Effects of Hydralazine versus Propranolol on Blood Velocity Patterns in Patients with Carotid Stenosis
Authors: Spence J. David
Published: August 2015

1. Since endothelial damage due to flow disturbances is of postulated significance in the pathogenesis of atherosclerosis, this study examined the effects of antihypertensive drugs on carotid flow patterns in patients with known carotid stenosis. A Doppler Echoflow unit was used to display arterial velocities in red (normal range), yellow (increased velocity) and blue (abnormally increased velocity thought to represent turbulence and other departures from laminar flow).

2. Twenty patients were studied before drug, then during intravenous administration of hydralazine, 6–12 mg, and propranolol, 2–5 mg, over 10–15 min each, with return to baseline between drugs.

3. After hydralazine, the occurrence of abnormal high velocity flow patterns increased in 17 of 20 patients; there was no change in three patients. Propranolol reduced the occurrence of abnormal high velocity flow patterns in 19 of 20 patients (P < 0.00001; chi-square).

4. These effects of antihypertensive drugs on arterial velocity patterns may be important in the selection of antihypertensive drugs to prevent or minimize the progression of atherosclerosis.
Increased Folate Catabolism in Mice with Ascitic Tumours
Authors: Kelly D. A. , Scott J. M. , Weir D. G.
Published: August 2015

1. Folate deficiency is reported in association with certain malignant tumours, and it has been suggested that this arises from increased folate turnover and catabolism in such circumstances.

2. Using an experimental animal model to determine the rate of catabolism of [3H]pteroylglutamate (folic acid) by the quantitative estimation of the two urinary catabolites p-[3H]aminobenzoylglutamate and [3H]acetamidobenzoylglutamate, we have measured the rate of folate catabolism in mice with ascitic tumours.

3. There was a significant increase in the rate of catabolism in the mice with tumours compared with controls over a 10 day period. This was associated with the accumulation of ascitic fluid and an increase in the number of tumour cells in the treated animals.

4. The increase in catabolism appeared to be due to increased cell turnover of the tumour rather than an increase in cell mass, as the increase in mass of the tumour was negligible.
Patterns of Smoking: Measurement and Variability in Asymptomatic Smokers
Authors: Adams L. , Lee C. , Rawbone R. , Guz A.
Published: August 2015

1. Measurements of patterns of puffing (cigarette-holder pneumotachograph) and ventilation (plethysmography) were made in ten asymptomatic smokers during the smoking of a cigarette, on four separate occasions.

2. There were marked individual differences and these were consistent over 3–5 weeks. In itself, the pattern of smoking could be responsible for a threefold variation in smoke intake.

3. Puffing but not inhalation became less intense as a cigarette was smoked.

4. It was not possible to predict indices of absorption from smoking patterns.

5. Certain smoking patterns, e.g. small puff volume, low puff frequency, short duration of inhalation and expulsion of volume between puff and inhalation, may be less harmful than others and this may explain why some individuals remain healthy despite a lifetime of smoking.
Calcium Metabolism Evaluated by 47Ca kinetics: Estimation of Dermal Calcium Loss
Authors: Charles P. , Jensen F. Taagehøj , Mosekilde L. , Hansen H. Hvid
Published: August 2015

1. Seventy-seven calcium balance and 47Ca turnover studies were performed in normal volunteers (n = 15) and in patients with osteoporosis (n = 12), primary hyperparathyroidism (n = 8), osteogenesis imperfecta (n = 5), medullary carcinoma of the thyroid (n = 4), thyrotoxicosis (n = 2) and intestinal bypass for obesity (n = 11).

2. After intravenous injection of 20 μCi of 47Ca two retention curves of 47Ca were obtained: R1(t) directly measured on a whole-body counter and R2(t) calculated from the cumulated daily excretions of 47Ca in urine and faeces. The data were fitted to a modification of the continuously expanding exchangeable calcium pool model.

3. Dermal calcium loss was estimated from the serum 47Ca specific radioactivity curve and the constantly increasing difference between the two retention curves. The median dermal calcium loss in 77 studies was 1.50 mmol 24 h−1 1.73 m−2 (range 0.13-4.60).

4. The dermal calcium loss might be overestimated by redistribution of tracer or by eventual insufficient collection of urine and faeces. The possible influences of these errors have been evaluated.

5. Patients with primary hyperparathyroidism had a greater (P < 0.02) dermal calcium loss (2.64 mmol; range 0.80–4.50) than a control group (1.38 mmol; range 1.25–2.34).
Dissociation between Calcium and Phosphate Absorption in Nephrotic Syndrome
Authors: Farrington K. , Newman S. P. , Varghese Z. , Moorhead J. F.
Published: August 2015

1. Intestinal calcium and phosphate absorption have been measured in nine patients with nephrotic syndrome and normal renal function, by a combined radioisotope technique which allows simultaneous measurement of both quantities. The values obtained were compared with those obtained in 20 normal controls.

2. Calcium absorption in the nephrotic group was significantly lower than in the control group (P < 0.01), but phosphate absorption in the nephrotic group did not differ from controls.

3. This dissociation between calcium and phosphate absorption provides further evidence for independent mechanisms governing the two absorption processes.
Biochemical Analysis of Hepatic Lipid in Alcoholic and Diabetic and Control Subjects
Authors: Cairns S. R. , Peters T. J.
Published: August 2015

1. Percutaneous needle biopsy specimens of liver were obtained from alcoholic, diabetic and control patients. Micro-methods of lipid separation and quantification were employed to determine the detailed nature of hepatic lipid.

2. Triglyceride is the major accumulating liver lipid in both alcoholic and diabetic patients. Cholesteryl ester levels were raised in both alcoholic and diabetic patients but only diabetic patients had significantly increased free cholesterol and phospholipid levels. Determination of phospholipid/free cholesterol ratios revealed a significant decrease in alcoholic cirrhosis compared with controls.

3. Fatty acid ester analysis of hepatic phospholipid and triglyceride revealed significant differences between alcoholic patients and controls but not between diabetic patients and controls. An increased ratio of non-essential/essential fatty acids was found in the patients with alcoholic liver disease whereas those of diabetic patients were similar to the controls.
Responses of the Systemic Circulation and of the Renin—Angiotensin—Aldosterone System to Ketanserin at Rest and Exercise in Normal Man
Authors: Fagard Robert , Cattaert Anne , Lijnen Paul , Staessen Jan , Vanhees Luc , Moerman Emmanuel , Amery Antoon
Published: August 2015

1. The systemic circulation at rest and during exercise was studied in ten normal male volunteers, after placebo on one occasion and after acute intravenous administration of the serotonergic antagonist ketanserin on another occasion. The effects of ketanserin on the components of the renin—angiotensin—aldosterone system, on plasma catecholamines and on exercise capacity for graded uninterrupted exercise were also investigated.

2. At rest in recumbency rapid intravenous injection of 10 mg of ketanserin, followed by a continuous infusion of 2 mg/h, produced an acute but transient fall in mean intra-arterial pressure of 6 mmHg compared with placebo. After 15 min the mean arterial pressure with ketanserin was within 2 mmHg of the mean pressure with placebo. In the sitting position both at rest and up to 30% of maximal work rate, the mean arterial pressure during ketanserin did not differ from the pressure on placebo. However, at higher levels of physical activity the rise in mean arterial pressure was lower with ketanserin; the pressure achieved with placebo was 7.5 mmHg higher at maximal work rate. Heart rate and cardiac output were significantly higher during ketanserin.

3. When the subjects were lying down and resting, plasma noradrenaline and adrenaline levels, plasma renin activity and angiotensin II concentration were not affected by ketanserin; however, these values were higher in the sitting position both at rest and during exercise. Plasma aldosterone was reduced by ketanserin during exercise and also when the subject was resting in the recumbent position.

4. Exercise capacity as measured by peak oxygen uptake was similar during ketanserin (3.09 ± se 0.12 litres/min) and during placebo (3.11 ± 0.13).

5. The data suggest that 5-hydroxytryptamine can have only a small role, if any, in pressure homoeostasis in sodium replete man at rest in recumbency. At moderate and heavy levels of exercise, the results are compatible with a role for 5-hydroxytryptamine in pressure regulation. Activation of the sympathetic nervous system by ketanserin is suggested by increases of plasma catecholamines, heart rate, cardiac output and plasma renin. The suppression of plasma aldosterone suggests that 5-hydroxytryptamine may have a role in the regulation of aldosterone secretion which is independent of angiotensin II.
The Effect of Leucocyte Elastase on the Immunoelectrophoretic Behaviour of α1-Antitrypsin
Authors: Stockley R. A. , Afford S. C.
Published: August 2015

1. Two-dimensional immunoelectrophoresis and conventional sodium dodecyl sulphate-polyacryl-amide gel electrophoresis was performed on various mixtures of purified α1-antitrypsin (α1AT) and leucocyte elastase (LE).

2. The results confirm that α1AT inhibits LE by the formation of enzyme-inhibitor complexes demonstrable by both techniques.

3. The complexes break down with time and are not affected by pH in the presence of excess α1AT. However, the breakdown is more rapid in the presence of excess enzyme only at pH values where LE remains active. The resultant products of the complex breakdown include inactivated LE and α1AT that has undergone limited proteolysis.

4. It is concluded that the presence or absence of α1AT-enzyme complexes as demonstrated by two-dimensional immunoelectrophoresis must be interpreted with caution when studying α1AT function in lung secretions. The absence of such complexes does not mean that previous interaction with enzyme has not occurred, thereby accounting for a reduction in α1AT inhibitory capacity.
Experimental Mouse Muscle Damage: The Importance of External Calcium
Authors: Jones D. A. , Jackson M. J. , McPhail G. , Edwards R. H. T.
Published: August 2015

1. The involvement of extracellular calcium in experimental muscle damage has been studied in an isolated mouse soleus muscle preparation.

2. The enzyme efflux and ultrastructural damage seen after excessive contractile activity were markedly reduced when the extracellular calcium was withdrawn. Low extracellular calcium also protected against the large enzyme efflux seen after treatment with low concentrations of detergent.

3. Treatment of the muscle with the calcium ionophore A 23187 caused significant release of enzyme from the muscle.

4. Nifedipine did not prevent the enzyme release after stimulation and although in some circumstances verapamil appeared to have some protective effect this was probably due to a local anaesthetic action on the muscle and not to any specific effect on calcium movement.

5. It is concluded that extracellular calcium is important in mediating at least the two forms of muscle damage studied here.
The Effect of Prostaglandin E2 Upon the Biochemical Response to Infused Angiotensin II in Human Pregnancy
Authors: Pipkin F. Broughton , Hunter J. C. , Turner S. R. , O'Brien P. M. S.
Published: August 2015

1. The effects of angiotensin II infusion without and with simultaneous infusion of prostaglandin E2 were studied in 25 women in second trimester pregnancy. Twenty received one infusion of angiotensin II alone, followed by its infusion simultaneously with prostaglandin E2; five received two identical infusions of angiotensin II alone as controls.

2. Angiotensin II infusion alone was associated with suppression of plasma renin concentration to levels inversely proportional to the evoked change in diastolic blood pressure. Plasma renin substrate concentration was unchanged, but plasma aldosterone concentration rose markedly. This rise was inversely proportional to the threshold for pressor effect of angiotensin II.

3. Prostaglandin E2 administration alone was associated with increased plasma renin concentrations.

4. The pressor effect of angiotensin II was blunted when given together with prostaglandin E2 and plasma concentrations of angiotensin II reached were lower.

5. Plasma renin concentration was again suppressed during the joint infusion regimen; the degree of suppression was inversely proportional to the change in diastolic pressure. Plasma aldosterone concentration rose, but did not differ in the control and experimental groups.

6. Thus although the renin-angiotensin system is stimulated in normal pregnancy, the normal control mechanisms are still functional, and the capacity for further increases in activity exists.
Urinary 6-Ketoprostaglandin F1α in Genetically Hypertensive Rats of the Lyon Strain
Authors: Benzoni D. , Vincent M. , Sassard J.
Published: August 2015

1. In order to assess the pathophysiological role of renal prostacyclin in genetic hypertension, the urinary excretion of its main stable metabolite, 6-ketoprostaglandin F1α, was followed in 12 hypertensive, normotensive and low blood pressure female rats of the Lyon strains at the ages of 5,9, 21, 32 and 45 weeks.

2. The urinary excretion of 6-ketoprostaglandin F1α, which progressively decreased in the three strains between 5 and 21 weeks of age, was found to be increased in 5- and 9-week-old hypertensive rats and it was reduced in 5-week-old low blood pressure rats, compared with age-matched normotensive controls.

3. The urinary 6-ketoprostaglandin F1α was found to be significantly related to the systolic blood pressure in 5- and 9-week-old rats of the three strains (r = 0.42; n = 71; P<0.001).

4. These results exclude a primary role in the development of hypertension for a genetically determined defect in the renal biosynthesis of prostacyclin in the spontaneous hypertensive rat of the Lyon strain.
The Effects of Magnesium on Ion Transport in Short-Circuited Rabbit Terminal Ileum
Authors: Booth I. W. , Milla P. J. , Harries J. T.
Published: August 2015

1. The effects of MgCl2 on the electrical characteristics and sodium and chloride transport in short-circuited rabbit terminal ileum in vitro were studied.

2. Increasing the magnesium concentration from a basal concentration of 1.1 mmol/l to either 2.5 or 10.3 mmol/l (mucosal or serosal addition) resulted in increases in the unidirectional flux of chloride from serosa to mucosa (JCl sm), short-circuit current (SCC) and transmucosal potential difference (p.d.).

3. Increasing the magnesium concentration from a low basal concentration (0.3 mmol/l) to 10.3 mmol/l (mucosal or serosal addition) abolished net sodium absorption and converted net chloride absorption into net secretion, as a result of a decrease in the unidirectional flux of sodium from mucosa to serosa (JNa ms), and increases in the unidirectional fluxes of sodium and chloride from serosa to mucosa (JNa sm and JCl sm). Increases in SCC and p.d. occurred after mucosal, but not serosal, addition of magnesium.

4. Incubation of stripped ileal mucosa with MgCl2 (10.3 mmol/l) did not result in increased mucosal concentrations of cAMP or cGMP.

5. These data suggest that at least part of the carthartic effect of magesium salts is likely to result from marked changes in ileal ion transport and provide a rational explanation for the watery diarrhoea commonly seen after the oral administration of magnesium salts to hypomagnesaemic patients.
Effect of An Intraluminal Food-Bulk on Low Calorie Induced Hyperbilirubinaemia
Authors: Ricci Giovanni L. , Ricci Riccardo R.
Published: August 2015

1. To test the hypothesis that the presence of food in the intestine plays a role in the control of serum bilirubin levels, the effect of a 1674 kJ (400 kcal) diet, including non-absorbable material able to produce an intestinal bulk, was compared with the effect of caloric restriction alone.

2. In normal individuals (n = 10) the rise of plasma bilirubin was comparable after the two trials. In patients with Gilbert's syndrome (n = 18), bilirubin concentration rose to a much greater extent during the caloric restriction as compared with controls, and to a lesser extent (P<0.001) after the bulky diet, as compared with caloric restriction alone in the same patient.

3. It is proposed that a factor originating from the intestine, perhaps a hormone, the release of which is dependent on the presence of food-bulk, plays a role in the control of hyperbilirubinaemia associated with caloric restriction.
Adrenoceptor Function and Ageing
Authors: Kelly John , O'malley Kevin
Published: August 2015

Introduction: The possible effect of ageing on adrenergic mechanisms has been one of the most studied of the pharmacodynamic processes affecting responsiveness to drugs in old age. Drugs may exert their primary effect by acting on the sympathetic nervous system or unwanted drug effects may be the result of perturbation of normal sympathetic nervous system function. Because of the important role of the sympathetic nervous system in drug action, it is not surprising that those interested in ageing and drug response should examine various aspects of this system.
Factor XII and Prekallikrein—Kallikrein—Kinin in the Cryoactivation of Human Plasma Prorenin
Authors: Brown C. F. , Osmond D. H.
Published: August 2015

1. Cryoactivation of human plasma ‘prorenin’ was followed for 24 h at −4°C. Chromogenic assays were used to determine factor XII (FXII), FXIIa, prekallikrein and kallikrein in relation to the observed cold-induced increase in plasma renin activity (PRA). Bradykinin activity was also determined using the rat uterus bioassay.

2. PRA increased rapidly and became significantly higher after just 6 h of cryoactivation, by which time prekallikrein had almost disappeared, while kallikrein and kinin levels increased. In contrast, FXII did not change notably, but some FXIIa was indeed formed.

3. The bacteriostat neomycin sulphate did not affect the course of cryoactivation, but did block the dextran sulphate- and kaolin-induced activation of prekallikrein and FXII respectively, and was therefore omitted.

4. Thus cryoactivation of prorenin is accompanied by, and may depend upon, the activation of FXII and prekallikrein, supporting other evidence in favour of this hypothesis.
Muscarinic Cholinergic Receptors in Peripheral Lung Tissue of Normal Subjects and of Patients with Chronic Obstructive Lung Disease
Authors: Raaijmakers J. A. M. , Terpstra G. K. , Van Rozen A. J. , Witter A. , Kreukniet J.
Published: August 2015

1. Muscarinic cholinergic receptors have been identified and characterized by radioligand binding studies in human peripheral lung tissue. The tissue was obtained at thoracotomy of 12 patients, of whom four had chronic obstructive lung disease.

2. The radioligand l-quinuclidinyl[phenyl-4-3H]benzilate (3H-QNB) was used to label the muscarinic cholinergic receptors. Binding was saturable, protein dependent and showed a high affinity and stereospecificity. Specific binding could be inhibited by agonists and antagonists; molar inhibition constants determined for the agents used were of the same order of magnitude as those reported for 3H-QNB inhibition in various tissues of laboratory animals. Inhibition experiments with agonists resulted in Hill slopes which were significantly different from unity, indicating multiple binding sites. The stable GTP analogue guanyl-5′-imidodiphosphate had no effect on the Hill slopes of agonists or antagonists.

3. The number of binding sites was significantly less in lung tissue from patients with chronic obstructive lung disease.
Effect of alcohol withdrawal on blood pressure, plasma renin activity, aldosterone, cortisol and dopamine β-hydroxylase
Authors: Bannan L. T. , Potter J. F. , Beevers D. G. , Saunders J. B. , Walters J. R. F. , Ingram M. C.
Published: August 2015

1. Sixty-five alcoholic patients admitted for detoxification had blood pressure, withdrawal symptoms, plasma cortisol (PC) and plasma aldosteron (PA) levels, plasma renin activity (PRA), and serum dopamin β-hydroxylase (DBH) levels measured on the first and fourth days after admission.

2. On the morning after admission blood pressure was elevated (>140/90) in 32 patients (49%) and was 160/95mmHg or more in 21 (32%). PRA was initially elevated in 41 patients, PA levels in 14, and 13 patients had raised PC levels. By the fourth day, blood pressure and bio-chemical measures had fallen significantly while urine volume and sodium output, low on admission, had increased significantly. On admission urinary metanephrine levels were raised in four out of the 31 patients who had them measured.

3. The height of both the systolic and diastolic blood pressures was significantly related to the severity of the alcohol. withdrawal symptoms. Of the biochemical parameters measured, PC level correlated with systolic but not diastolic pressure, and urinary volume was inversely correlated with the height of the diastolic pressure. No relationship was found between blood pressure and PRA or PA level.

4. The pressor effect of alcohol withdrawal could be due to sympathetic nervous system overactivity, or possibly to hypercortisolaemia. The first hypothesis seems more likely.
Further analysis of cell membrane changes in genetic hypertension in rats by diphenylhexatriene fluorescence polarization
Authors: Aracon-Birlouez I. , Montenay-Carestier T. , Devynck M. A.
Published: August 2015

1. Fluorescence Dolarization of dbhenvlhexa-triene embedded in membranes was used as an index of ‘microviscosity’ in platelets and ervthro—cyte ghosts of spontaneously hypertensive rats of the Okamoto-Aoki strain (SHR), Wistar-Kyoto strain (WKY) and of the hypertension-prone and -resistant Sabra strains (SBH and SBN), and the original Sabra strain (SB).

2. Microviscosity was increased both in erythrocyte ghosts and platelet membranes of male but not female SHR rats compared with WKY rats and in hypertension-prone Sabra rats compared with the original Sabra rats.

3. Acute and chronic salt loading increased the microviscosity of platelet membranes in all strains of rats but had no effect on the erythrocyte membranes.

4. Microviscosities of vesicles made of lipids extracted from SHR and WKY erythrocyte ghosts were similar. This supports the hypothesis that membrane proteins play a major role in the differences in microviscosity observed in SHR rats.
Sir George Pickering (1904–1982)
Authors: Peart W. S.
Published: August 2015

I first met George Pickering when I was a medical student in the Anatomy Department at St Mary's Hospital Medical School. He brought an amputated leg which had arteriovenous anastomoses within it, leading to overgrowth of the limb and subsequently to amputation to try and correct the high cardiac output and failure which it caused. He had injected the arteries with a barium paste and wanted someone to try and find the connections by simple dissection. As I liked dissection, I volunteered, and though I was unable to show any major connections, which were presumably at arteriolar-venular level, it was to mark the beginning of a very long apprenticeship.