bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Presynaptic α-Adrenoceptor-Mediated Regulation of Noradrenaline Release in the Isolated Perfused Kidney of Spontaneously Hypertensive Rats
Authors: Ekas R. D. , Steenberg M. L. , Lokhandwala M. F.
Published: August 2015

1. Release of [3H]noradrenaline during peri-arterial nerve stimulation and its inhibition by the presynaptic α-adrenoceptor mechanism were studied in the isolated perfused kidney from spontaneously hypertensive and Wistar-Kyoto rats.

2. A frequency related vasoconstriction as well as [3H]noradrenaline release were observed over the stimulating range of 0.25-32 Hz in both the Wistar-Kyoto and spontaneously hypertensive rats. The spontaneously hypertensive rat kidneys exhibited both an increased vasoconstrictor response and a greater [3H]noradrenaline release when compared with the Wistar-Kyoto rat kidneys.

3. Presynaptic inhibition of [3H]noradrenaline release was evaluated at 2 Hz by using the α-adrenoceptor agonist, tramazoline. Increasing concentrations of tramazoline from 2 × 10−9 mol/l to 2 × 10−7 mol/l caused a dose-dependent decrease in the stimulus-induced release of [3H]noradrenaline in spontaneously hypertensive rats but not in Wistar-Kyoto rats. Only 2 × 10−7 mol/l tramazoline had an inhibitory effect in the Wistar-Kyoto rats.

4. These data indicate that noradrenaline release during sympathetic nerve stimulation is greater in the spontaneously hypertensive rat. The supersensitivity of presynaptic α-adrenoceptors observed in spontaneously hypertensive rats may be a consequence of the greater noradrenaline release present in these animals.
Effect of an Anteroventral Third-Ventricle Lesion on Sodium Chloride Hypertension in Dahl S Rats
Authors: Goto Atsuo , Ganguli Mukul , Tobian Louis , Johnson Mary Ann , Iwai Junichi
Published: August 2015

1. After a lesion had been made in the anteroventral third ventricle (AV3V), Dahl S rats received daily injections of either pitressin (500 m-units/kg) or vehicle during 10 weeks of high (8%) NaCl diet. Rats with sham lesions served as controls. The blood pressure in sham-lesion rats receiving vehicle was 189 mmHg after 10 weeks of high NaCl diet. Lesion rats given vehicle showed a 60% smaller increase in blood pressure than sham-lesion rats (P < 0.001), the blood pressure averaging 161 mmHg at 10 weeks.

2. Lesion rats given pitressin also showed a smaller increase in blood pressure than sham-lesion rats (P < 0.05), but the final blood pressure averaged 176 mmHg and was significantly higher than that of lesion rats given vehicle (P < 0.025). Pitressin injections corrected the hypernatraemia in lesion rats.

3. In another experiment, the effect of the AV3V lesion on the renal papillary plasma flow (RPPF) in Dahl S rats was studied. Dahl S rats have a lower RPPF than Dahl salt-resistant (R) rats even on a low NaCl intake. The AV3V lesion increased the RPPF by 14% in S rats (P < 0.025).

4. These findings suggest that NaCl-induced hypertension in Dahl S rats requires the integrity of the AV3V region for its full expression, and the ability of the AV3V lesion to attenuate the NaCl-induced hypertension in Dahl S rats is partly related to the attenuation of vasopressin release. Moreover, the AV3V lesion partly corrected one of the characteristic features of Dahl S rats: the reduction in RPPF compared with Dahl R rats on a low NaCl intake.
Renal Function and Sympathetic Activity during Mental Stress in Spontaneously Hypertensive Rats
Authors: Lundin S. , Thorén P.
Published: August 2015

1. The role of the renal sympathetic nerves in the urinary sodium excretion response to ‘mental stress’ in spontaneously hypertensive rats (SHR) and in Wistar-Kyoto normotensive (WKY) rats was examined. Urinary sodium excretion was measured during ‘rest’ and during a 20 min period of ‘mental stress’ in intact rats and in renal denervated rats. Under similar conditions renal sympathetic activity was also measured in a separate group of rats.

2. Urinary sodium excretion fell more during the stress period in SHR (-64 ± 5%) than in WKY rats (-34 ± 7%), despite a greater arterial pressure increase in SHR. This greater decrease in sodium excretion appeared to result from both a more pronounced reduction in GFR and a greater increase in tubular sodium reabsorbtion.

3. Renal sympathetic nerve activity, which was higher at rest in SHR than in WKY rats, increased much more in SHR than in WKY rats during stress. This may explain the greater reduction in sodium excretion in SHR during stress, because renal denervation almost abolished this latter response.

4. The neurogenically elicited renal response might contribute in an important way to the early development of SHR hypertension. Renal denervation, as well as attenuating sodium retention, also delays the pressure rise in the young SHR.

5. The initial tachycardia after mental stress gradually subsided towards the end of the stress period in SHR, whereas renal sympathetic activity remained elevated. This indicates that the increase in heart rate, if anything, may underestimate the true extent of sympathetic activation in for example the renal and splanchnic regions during arousal.
Endogenous Opioids Modulate Central Nervous System Blood Pressure Control in Man
Authors: Rubin P. C. , McLean Kathleen , Reid J. L.
Published: August 2015

1. Two studies were performed to elucidate the role of opioids in blood pressure control in man.

2. Study 1: nine normal subjects, 18–32 years, received in a randomized single blind manner, volume matched infusions of a Met-enkephalin analogue (DAMME) 0.5 mg, naloxone 0.2 mg/kg or saline. Blood pressure, heart rate and plasma noradrenaline were determined supine and after a 5 min, 70° head-up tilt at 0, 3/4, 2, 3, 4, 5 and 6 h.

3. Study 2: seven subjects, after baseline recordings of blood pressure and heart rate received six incremental infusions of sodium nitroprusside, 1.5–7.5 μg min−1 kg−1. They then received DAMME or naloxone and the nitroprusside infusions were repeated between 3 and 4 h. There was a significant linear relationship between fall in mean arterial pressure and rise in heart rate in each case and the slope was used as an index of baroreflex sensitivity.

4. Neither naloxone nor DAMME influenced supine blood pressure or heart rate. Blood pressure after head-up tilt was significantly (analysis of variance) decreased by DAMME for up to 5 h but not by naloxone, the effect being most marked at 3 h: systolic (mean ± sd), placebo 110 ± 6, naloxone 106 ± 10, DAMME 96 ± 16 (P< 0.02); diastolic (mean ± sd), placebo 78 ± 7, naloxone 79 ± 5, DAMME 67 ± 8 (P < 0.01). The increases in heart rate and plasma noradrenaline on tilting after DAMME were not significantly different from values with placebo or naloxone. The 3 h values for heart rate were: placebo 87 ± 16, naloxone 88 ± 19, DAMME 89 ± 23 (P > 0.1); for plasma noradrenaline (nmol/l): placebo 6.0 ± 2.2, naloxone 5.8 ± 1.9, DAMME 6.0 ± 1.9 (P > 0.1).

5. Naloxone significantly increased the slope (beats per min/mmHg) of the regression relationship from a mean of 1.8 ± 0.07 to 3.0 ± 1.3 (P < 0.05), and DAMME reduced the slope from 2.7 ± 1.7 to 1.2 ± 0.5 (P < 0.05).

6. We conclude that endogenous opioids modulate baroreflex function in man.
Reversal of Left Ventricular Hypertrophy after Treatment of Hypertension by Atenolol for One Year
Authors: Sau F. , Cherchi A. , Seguro C.
Published: August 2015

1. Fifteen patients with essential hypertension, class I, II WHO, nine males and six females, whose mean age was 46 years, were given atenolol, 100 mg a day, for 1 year.

2. After 1 month, compared with control, systolic and diastolic blood pressures, heart rate and cardiac output were reduced, whereas left ventricular end-diastolic dimension and stroke volume were increased and total vascular resistances, wall stress, left ventricular mass and h/diastolic radius (R) ratio were unchanged.

3. After 1 year, compared with control, systolic and diastolic blood pressures, heart rate and cardiac output were still reduced, total vascular resistance and wall stress were unchanged. End-diastolic dimension and stroke volume reverted to previous values; left ventricular mass and h/R ratio were significantly decreased.

4. These results show that left ventricular hypertrophy in essential hypertension can revert after 1 year of treatment with atenolol, at least in relatively young people. Since the left ventricle wall stress was not changed after atenolol, the regression of left ventricle hypertrophy seems prevalently to be related to the decrease of adrenergic activity of the heart.
Role of Adrenergic Overactivity and Pressure Overload in the Pathogenesis of Left Ventricular Hypertrophy in Borderline and Sustained Essential Hypertension in Man
Authors: Corea Luigi , Bentivoglio Maurizio , Verdecchia Paolo , Motolese Mario
Published: August 2015

1. In 16 borderline and 18 sustained hypertensive patients, interventricular septal thicknesses (by echocardiography) were greater than those found in 18 healthy subjects. Values in borderline and sustained hypertensives did not differ significantly.

2. In healthy subjects and borderline hypertensive patients, posterior wall thicknesses were normal, whereas they were greater in sustained hypertensive patients than in the former two groups.

3. In borderline hypertension, interventricular septal thickness was positively correlated with resting supine (r = 0.89, P < 0.001) as well as upright (r = 0.60, P < 0.01) plasma noradrenaline, but not with adrenaline, plasma renin activity and mean blood pressure.

4. In sustained hypertension, posterior wall thickness was positively correlated with mean blood pressure (r = 0.85, P < 0.001), but not with noradrenaline, adrenaline and plasma renin activity.

5. In human hypertension, left ventricular hypertrophy seems to involve only the interventricular septum in the borderline stage, extending to the posterior wall in the sustained stage. Adrenergic overactivity could play an important role in development of interventricular septal hypertrophy in borderline hypertension, whereas pressor factors could be mainly involved in the development of posterior wall hypertrophy in sustained hypertension.
Anatomical and Physiological Aspects of Cardiovascular Function in Wistar—Kyoto and Spontaneously Hypertensive Rats at Birth
Authors: Gray Sarah D.
Published: August 2015

1. The present study was designated to determine whether there are any detectable differences in cardiovascular anatomy or physiology between Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) pups at birth.

2. It was found that mean arterial pressures were significantly higher, heart rates were slightly higher, and heart weight/body weight ratios were higher in SHR.

3. Vascular dimensions were determined in a small sample of those rats, and the data there also indicate hypertrophy to some degree: the ratio of wall thickness/lumen radius was higher in SHR, tangential wall tension and number of cell layers in the media were increased.

4. It is concluded that some of the concomitant features of hypertension, such as left ventricular wall hypertrophy and arterial wall hypertrophy, may be genetically determined to some extent in SHR.
Body Fat and Glucose Tolerance in Early Blood Pressure Elevation: Its Relation to Arteriolar Hypertrophy
Authors: Andersson Ove , Sivertsson Ramon , Sannerstedt Rune , Beckman Marie , Magnusson Marie , Sjöström Lars , Björntorp Per
Published: August 2015

1. Forty-four young men with blood pressure elevation and 29 age-matched volunteer subjects were examined with invasive blood pressure and cardiac output measurements. The regional blood flow resistance of the hand during hyperaemia was calculated from blood pressure and flow data from venous occlusion plethysmography.

2. In a re-examination 5 years later the same protocol was applied and an oral glucose tolerance test was performed with glucose and insulin determinations. Body composition was calculated from total body potassium data (whole body 40K counter) and body weight.

3. Patients with blood pressure elevation were characterized by a significantly higher cardiac index at rest, and a significantly increased resistance during hyperaemia of the hand in comparison with that of the controls. The patients with blood pressure elevations were also divided according to cardiac output. The hyper-kinetic subgroup did not have an increased resistance during hyperaemia. Patients with blood pressure elevation had significantly increased body weight and body mass index in comparison with controls and there was a significant correlation between body wieght and regional resistance during hyperaemia.

4. In the re-examination it was found that the body weight difference between patients with blood pressure elevation and normotensive controls was explained by increased body fat. There was no difference in body weight between the normokinetic and hyperkinetic subgroups of patients with blood pressure elevation but the former group had significantly increased insulin concentrations on the glucose load.

5. Significant correlations were demonstrated between body weight, body fat and insulin concentration 30 min after glucose load against resistance during hyperaemia as the dependent variable. A multiple regression coefficient of 0.59 was found between the three independent variables and resistance during hyperaemia. Furthermore, the addition of the insulin concentration variable to the two independent variables body weight and body fat increased significantly the multiple regression coefficient.
Effects of Aging on the Variability of Arterial Pressure in Essential Hypertensive Patients
Authors: Ogawa Jun , Takata Shigeo , Nomura Gakuji , Arai Shiro , Ikeda Takayuki , Takabatake Toshikazu , Hattori Nobu
Published: August 2015

1. We studied the effects of aging on the variability of blood pressure in mild to moderate essential hypertensive subjects.

2. Cardiac index was greater and total peripheral resistance index was less in patients under 40 years (by an average of 1.06 litres min−1 m−2 and 9.23 mmHg 1−1 min−1 m−2) than in those over 40 respectively (P < 0.001 for each).

3. Pulse pressure/stroke volume was less by an average of 0.345 mmHg/ml in patients under 40 years than that in those over 40 (P < 0.001). Pulse pressure/stroke volume was correlated with age (r = 0.621), average systolic blood pressure (r = 0.623) and inversely with baroreflex sensitivity (r = −0.494).

4. Baroreflex sensitivity was less by an average of 3.1 ms/mmHg in patients over 30 years than in those under 30 (P < 0.025). Baroreflex sensitivity was inversely correlated with age (r = −0.617) and average systolic blood pressure (r = −0.589).

5. Beat by beat variability of systolic blood pressure was correlated with age (r = 0.460), particularly when the data of those in their twenties were excluded (r = 0.618), and significantly with pulse pressure/stroke volume (r = 0.650), average systolic blood pressure (r = 0.618) and inversely with baroreflex sensitivity (r = −0.477). These relationships were not observed for diastolic blood pressure.

6. Maximum difference in systolic blood pressure in a day was correlated with pulse pressure/stroke volume (r = 0.482) and average systolic blood pressure (r = 0.648) but not with baroreflex sensitivity. These relationships were not observed for diastolic blood pressure.

7. Variability of systolic blood pressure in patients over 30 years gradually increased with age. In contrast, those of systolic and diastolic blood pressures in subjects in their twenties were relatively large. This might be related to factors other than aging, presumably those which underlie the hyperdynamic circulatory state.
Greater Antihypertensive Efficacy of the Calcium Channel Inhibitor Verapamil in Older and Low Renin Patients
Authors: Bühler Fritz R. , Hulthén U. Lennart , Kiowski Wolfgang , Bolli Peter
Published: August 2015

1. The calcium slow channel inhibitor verapamil was administered as monotherapy (240-270 mg; mean 427 mg/day) on the average for 93 days to 43 patients with essential hypertension; 11 with low, 24 with normal and eight with high renin sodium index.

2. Verapamil reduced blood pressure from 171 ± 16/108 ± sd 6 mmHg to 152 ± 14/93 ± 9 (both P < 0.001); in 25 of the 43 patients a diastolic pressure ≤95 mmHg was achieved. Two patients each reported vertigo, sleeplessness and constipation.

3. The fall in mean blood pressure after verapamil was directly related to age (r = 0.759, P < 0.001), pretreatment mean blood pressure (r = 0.701, P < 0.01) and plasma noradrenaline concentration (r = 0.400, P < 0.05), and inversely related to plasma renin activity (r = −0.551), P < 0.001). These correlations were also significant for diastolic blood pressure. Accordingly, the antihypertensive response to verapamil was greatest in older and low renin patients.

4. This greater blood pressure decrease with verapamil in older and low renin patients suggests a greater calcium influx-dependent vasoconstriction in these patients, which seems to be directly related to the activity of the sympathetic nervous system.
Effect on High Density Lipoprotein Cholesterol of Atenolol and Oxprenolol in Patients with Mild Essential Hypertension
Authors: Kjeldsen S. E. , Eide I. , Leren P. , Foss O. P.
Published: August 2015

1. Nineteen healthy men aged 50 years, with untreated, mild essential hypertension WHO group I, were randomized into two groups to study the effect of treatment (18 weeks) with oxprenolol (n = 10) and atenolol (n = 9) on serum cholesterol fractions, total triglycerides and uric acid.

2. Oxprenolol lowered high density lipoprotein (HDL) cholesterol by 11.4% (P < 0.02) and cholesterol ratio (HDL cholesterol × 100/LDL + VLDL cholesterol) by 13.7% (P < 0.05). Atenolol lowered HDL cholesterol by 16.5% (P < 0.02) and cholesterol ratio by 19.2% (P < 0.01).

3. Oxprenolol and atenolol raised total triglycerides by 20.0% and 17.9% respectively. Only with atenolol was this increment statistically significant (P < 0.05).

4. The HDL cholesterol lowering effect of oxprenolol and atenolol observed in the present study may have clinical importance, since such metabolic side effects have been postulated to counteract the beneficial effect of blood pressure reduction on development of atherosclerosis and coronary heart disease in mild essential hypertension.
Cholinergic Manifestations of the Acute Autonomic Reaction to Hypoglycaemia in Man
Authors: Corrall R. J. M. , Frier B. M. , Davidson N. McD. , Hopkins W. M. , French E. B.
Published: August 2015

1. The effects of insulin-induced hypoglycaemia on pupil size, parotid salivary secretion and sweating were studied in seven normal volunteers.

2. Hypoglycaemia was associated with an acute stimulation of parotid salivary secretion and of sweating, synchronous in onset with the rise in heart rate. There was no clear evidence of concurrent pupillary constriction.
Relationship between Primary Biliary Cirrhosis and Chronic Graft versus Host Disease: Investigation of Histocompatibility (HLA) Antigenic Determinants in Biliary Tract Antigens
Authors: McFarlane I. G. , McFarlane B. M. , Haines A. J. , Eddleston A. L. W. F. , Williams Roger
Published: August 2015

1. According to a recent hypothesis, based on similarities between chronic graft versus host disease and primary biliary cirrhosis (PBC), immune reactions against histocompatibility (HLA) antigens-6-be responsible for the bile duct damage and extrahepatic lesions of PBC.

2. Previous studies have demonstrated autoimmune reactions in PBC against normal human biliary tract antigens. To equate these findings with the above hypothesis, it has been suggested that the biliary antigens are related to the HLA system and, in the present study, this possibility has been investigated by: (a) using preparations of the biliary antigens to inhibit the lymphocytotoxic activity of standard HLA-typing sera against normal lymphocytes, and (b) employing guinea-pig antisera raised against the biliary antigens as ‘typing reagents’ in the lymphocytotoxicity test to determine whether these antisera recognize HLA components on the surfaces of normal lymphocytes.

3. No inhibition by the biliary antigens of the reaction of two standard typing sera against T-and B-lymphocytes from two normal healthy donors (covering nine HLA-A, -B, -C and three HLA-DR loci antigens) was observed. Conversely, the guinea-pig antisera showed no reaction against these lymphocytes.

4. The results suggest that the biliary tract antigens are probably not related to ‘common’ antigenic determinants associated with the HLA system.
Trypsin-Activatable Inactive Renin in Rat Plasma
Authors: Glorioso Nicola , Madeddu Paolo , Dessi'-Fulgheri Paolo , Fois Giuseppe , Meloni Franca , Bandiera Francesco , Tonolo Giancarlo , Rappelli Alessandro
Published: August 2015

1. Activation of inactive renin in rat plasma has been studied with different trypsin concentrations and incubation times at pH 6.2 and 4°C.

2. Trypsin concentrations below 2 mg/ml, lower than endogenous rat plasma anti-trypsin activity, do not activate inactive renin, whereas maximal activation is obtained with trypsin at 6 mg/ml for 1 min at 4°C, pH 6.2.

3. Under these conditions trypsin can cleave dialysable fragments from renin substrate. ANG I can be generated at 37°C with a pH optimum of 5.3. Nevertheless, the ANG I formation at pH 6.2 was totally unaffected.

4. Incubations longer than 2 min with trypsin at 6 mg/ml can induce a direct cleavage of dialysable ANG I-containing fragments strongly interfering with the measurements of renin activity at pH 6.2.

5. On average 40% of the total renin measured in plasma of normotensive WK rats is in the inactive form, although a wide range of variation is observed.
Clearance and Non-Invasive Determination of the Hepatic Extraction of Indocyanine Green in Baboons and Man
Authors: Grainger S. L. , Keeling P. W. N. , Brown I. M. H. , Marigold J. H. , Thompson R. P. H.
Published: August 2015

1. The disposition of an intravenous bolus of indocyanine green (ICG) has been studied in healthy man and baboons using a novel analysis of a two compartment pharmacokinetic model.

2. This analysis enabled the hepatic extraction ratio (ER) of dye to be determined solely from the plasma disappearance curve, and the ER determined did not differ from that measured by hepatic vein catheterization.

3. When compared with clearance measured at steady state, the two compartment model gave a significantly more accurate determination of plasma clearance than did the conventional one compartment model.

4. It is concluded that, in health, liver blood flow may be calculated accurately and noninvasively after a single intravenous injection of ICG.
Recovery of Infused [14C]Bicarbonate as Respiratory 14CO2 in Man
Authors: Clugston Graeme A. , Garlick Peter J.
Published: August 2015

1. Nine adult subjects (eight obese, one normal) were infused with NaH14CO3 for up to 36 h.

2. The recovery of label as respiratory 14CO2 was close to 90% throughout and did not change with feeding or with dietary composition.
Baroreflex Function after Therapy Withdrawal in Patients with Essential Hypertension
Authors: Carretta Renzo , Fabris Bruno , Bellini Giuseppe , Tonutti Laura , Battilana Gabriella , Bianchetti Anna , Campanacci Luciano
Published: August 2015

Summary
Growth Hormone-Induced Changes in Myofibrillar Protein Breakdown in Hypopituitary Children
Authors: Ballard F. J. , Burgoyne J. L. , Tomas F. M. , Penfold J. L.
Published: August 2015

1. Creatinine and Nτ-methylhistidine excretion rates have been measured in 13 hypopituitary children to calculate the body muscle contents and rates of myofibrillar protein breakdown. Analyses have been made during periods of growth hormone withdrawal and subsequent administration.

2. The creatinine excretion rate was lower in the hypopituitary children, indicating a lower muscle content per kg body weight. This difference persisted even in children who had received growth hormone for several years.

3. Excretion of Nτ-methylhistidine was reduced by the administration of growth hormone.

4. The fractional breakdown rate of myofibrillar protein, as calculated from the Nτ-methylhistidine to creatinine molar excretion ratio, averaged 1.76%/day in the four youngest children during growth hormone withdrawal. This was significantly higher than for control children of a similar age (P < 0.02) and was reduced to the normal rate of 1.47%/day by growth hormone administration.

5. in older children the fractional rate of myofibrillar protein degradation remained in the normal range irrespective of growth hormone treatment.

6. These results are discussed in the context of the anabolic effects of growth hormone on muscle being partly explained by its action to decrease rates of protein breakdown.
Post-Adrenalectomy Hypotension in Rats; Absence of Baroreflex Resetting or Effect of Naloxone
Authors: Gardiner S. M. , Bennett T.
Published: August 2015

1. Male Wistar rats were either bilaterally adrenalectomized or sham-operated, and given 1% sodium chloride solution instead of tap water to drink. Seven days later, arterial blood pressures were recorded directly from conscious freely moving rats.

2. Systolic and diastolic blood pressures were significantly lower in the adrenalectomized rats, whereas heart rates were significantly higher than in sham-operated animals. The tachycardia was due to a combination of sympathetic hyperactivity and reduced vagal tone, which may have been reflex responses to a reduction in effective blood volume.

3. Baroreflex control of the sinus node was assessed from the pulse interval responses to rises (induced by methoxamine) or falls (induced by glyceryl trinitrate or sodium nitroprusside) in systemic arterial blood pressure. The relation between pulse interval and systolic blood pressure was described by the same curve in sham-operated and adrenalectomized rats, indicating that, in the latter, there was no change in baroreflex setting or sensitivity.

4. Intravenous administration of naloxone (2mg/kg) had no effect on systemic arterial blood pressure in adrenalectomized rats, suggesting that endogenous opiates were not contributing to the hypotension.
The Presence in Normal Plasma, Serum and Platelets of Factors That Stimulate the Production of Prostacyclin (PGI2) by Cultured Endothelial Cells
Authors: Seid J. M. , Jones P. B. B. , Russell R. G. G.
Published: August 2015

1. The effect of plasma and serum from normal subjects on the production of prostacyclin by cultured porcine endothelial cells was investigated.

2. Both plasma and serum from all subjects studied significantly stimulated the production of prostacyclin by cultured endothelial cells, measured by the radioimmunoassay of its stable metabolite 6-oxoprostaglandin F1α.

3. Serum caused a consistently greater stimulation than plasma from the same individual. The stimulation was dose-dependent and inhibited by indomethacin. Heparin added to serum also inhibited this response.

4. Extracts from isolated washed platelets were tested for their ability to increase prostacyclin production. Extracts from platelets which had been induced to aggregate and release their granule contents in response to thrombin, caused stimulation.

5. These results indicated the invariable presence in plasma and serum of factors that stimulate the production of prostacyclin by endothelial cells in vitro. At least one of these factors is derived from platelets. These factors may be involved in the regulation of prostacyclin production by the vascular endothelium under normal conditions and in disease states.
A Signal Detection Theory Analysis of the Effect of Chest Cage Restriction upon the Detection of Inspiratory Resistive Loads
Authors: Narbed P. G. , Marcer D. , Howell J. B. L. , Spencer E.
Published: August 2015

1. By the use of Signal Detection Theory techniques, resistive load detection sensitivity was estimated in six normal subjects, and compared with detection when the chest cage was strapped in the position of full expiration.

2. With chest cage restriction there was both a decrease in detection sensitivity and an increase in the willingness to report the presence of an added load to breathing.

3. This suggests that the similarity of detection in chest clamping and control previously reported was due partly to increased detection bias with chest clamping.

4. These results have implications concerning the dependence of detection on afferent information from the chest wall.
A Comparison of the Bronchodilator and Vasopressor Effects of Exercise Levels of Adrenaline in Man
Authors: Warren J. B. , Dalton N.
Published: August 2015

1. Plasma adrenaline was measured at rest and on exercise in six normal, non-atopic subjects. The exercise test produced a minimum tachycardia of 158 beats/min and a mean plasma adrenaline level of 1.89 nmol/l.

2. On a separate occasion, two doses of l-adrenaline (0.025 μg min−1 kg−1 and 0.05 μg min−1 kg−1) were infused in the same subjects at rest to produce two mean plasma levels similar to those found on exercise.

3. Significant bronchodilation and elevation of plasma glucose occurred with both infusion doses when compared with placebo.

4. Neither infusion caused a significant change in heart rate and only the higher dose caused a small but significant rise in systolic and fall in diastolic blood pressure.

5. Our results suggest that adrenaline as a hormone, at the levels found on exercise, is capable of causing bronchodilation and glycogenolysis in normal subjects. Its contribution to the cardiovascular response to exercise appears to be slight and suggests that its role in cardiovascular physiology may also be marginal.
Physical Exercise as Prophylaxis against Involutional Vertebral Bone Loss: A Controlled Trial
Authors: Krølner Bjørn , Toft Birte , Nielsen Stig Pors , Tøndevold Erik
Published: August 2015

1. The skeletal effects of physical training were studied in a controlled trial involving 31 healthy women (aged 50–73 years) with previous Colles' fracture of the forearm. The bone mineral content of the lumbar spine and both distal forearms was measured by dual-photon (153Gd) absorptiometry.

2. The participants were allocated to either a physical exercise group or a control group. The former group followed a standardized exercise programme, exercising for 1 h twice weekly during 8 months.

3. Twenty-seven women completed the study. Lumbar spine bone mineral content of the exercise group increased by 3.5%, whereas that of the control group decreased by 2.7%. The rate of bone loss in the control group equalled that of age-matched normal women.

4. The changes in forearm bone mineral content appeared to be independent of the exercise. The bone mineral content of the previously fractured forearm remained nearly unchanged. The bone mineral content of the uninjured forearm decreased on average by 3.5%.

5. The data suggest that physical exercise can inhibit or reverse the involutional bone loss from the lumbar vertebrae in normal women. Physical exercise may prevent spinal osteoporosis.
Intravenous Ethanol Can Provide Bronchodilatation in Asthma
Authors: Ayres Jon G. , Clark T. J. H.
Published: August 2015

1. The effect of intravenous infusions of saline, and 2, 4 and 8% (v/v in saline) ethanol on airflow were assessed in five normal male subjects and five male patients with asthma.

2. Normal subjects showed no response to intravenous ethanol at any dose.

3. in patients with asthma, specific airways conductance (sGaw) showed a sustained rise of approx. 32.8% from baseline with 8% ethanol which was not seen at lower doses. By contrast, salbutamol (400 μg by aerosol) caused a mean rise in sGaw of 84.4% from baseline.

4. Blood ethanol concentrations showed a sustained rise over the full duration of the study with 8% ethanol but not with lower doses.

5. Ethanol causes a sustained improvement in sGaw in patients with asthma (38.9% of the response to salbutamol) if blood ethanol levels are sufficiently elevated.
Haemodynamic Responses to Static and Dynamic Handgrip before and after Autonomic Blockade
Authors: Lewis Steven F. , Taylor W. Fred , Bastian Bruce C. , Graham Robert M. , Pettinger William A. , Blomqvist C. Gunnar
Published: August 2015

1. Six healthy men performed static and dynamic handgrip to local muscular fatigue in approximately 6 min under control conditions, i.e. without drugs and after combined para-sympathetic and β-adrenergic blockade with atropine and metoprolol.

2. From rest to exercise at fatigue, systolic, diastolic and mean arterial pressures increased by 32 ± 4 and 39 ± 3 mmHg, 24 ± 3 and 26 ± 4 mmHg, and 26 ± 3 and 30 ± 3 mmHg respectively for static and dynamic handgrip. There were no significant differences between the pressor responses for the two modes of contraction. Cardiac output increased significantly only during dynamic exercise. Total peripheral resistance increased by 2.3 ± 1.0 units for static handgrip (P < 0.05) and by 0.7 ± 0.8 unit (P > 0.05) for dynamic handgrip. Autonomic blockade abolished the heart rate response to both static and dynamic handgrip. For both modes of contraction the systolic arterial pressure responses were 9–12 mmHg lower (P < 0.05) after autonomic blockade, but the diastolic and mean pressure responses were not significantly affected. A significant increase in cardiac output persisted during dynamic exercise. The increase in peripheral resistance during static exercise tended to be greater after blockade. Plasma noradrenaline and adrenaline levels showed only minor elevations in response to static and dynamic handgrip and were not changed by autonomic blockade.

3. These data indicate that when performed to a common end-point with identical small muscle groups static and dynamic exercise produce an equally large pressor response, which is only slightly attenuated by autonomic blockade.
Effects of Acute Blood Volume Expansion on Vascular Resistance and Reactivity in Anaesthetized Dogs
Authors: Jandhyala Bhagavan S. , Hom Gary J.
Published: August 2015

1. The effects of acute volume expansion on vascular resistance and reactivity to noradrenaline and angiotensin II are reported in this study. The estimated circulating blood volume of pentobartibal-anaesthetized dogs was expanded by about 35% with equilibrated donor blood. The animals were bilaterally nephrectomized to sustain expanded volume.

2. Functional changes in vascular smooth muscle were determined in the flow controlled, vascularly isolated, denervated, perfused hind limb preparation in the same animal.

3. Systemic volume expansion per se had no immediate influence on vascular resistance. However, resistance in the hind limb, as determined by the shift of the pressure-flow curves, progressively increased 60 and 120 min after volume expansion. The changes noted after 120 min were significantly greater than those observed after 60 min.

4. The changes in vascular resistance were accompanied by potentiation of the vascular responses to noradrenaline but not to angiotensin II. Significant shifts which occurred in the noradrenaline dose-response curves were similar to those of the resistance curves.

5. in closely simulated control experiments in dogs whose kidneys were intact or had been removed, and whose blood had or had not been equilibrated with donor blood, the above-mentioned vascular changes were not observed in the absence of volume expansion.

6. It is suggested that the functional changes observed in the hind limb vasculature after volume expansion are related to the presence of a circulating substance. From the data obtained from the experimental model used in this study, it can be concluded that such a substance is not released from the kidney.
Hypokalaemia Stimulates Prostacyclin Synthesis in the Rat
Authors: GÜLlner Hans-Georg , Graf Andrew K. , Gill John R. , Mitchell Murray D.
Published: August 2015

1. To examine the hypothesis that the normalcy of blood pressure, despite an increase in circulating angiotensin II, and the blood pressor hyporesponsiveness to infusion of pressor agents which are associated with hypokalaemia, are due to overproduction of prostacyclin, the principal prostaglandin (PG) synthesized by the vascular endothelium, we studied the effect of experimental hypokalaemia on the urinary excretion of immunoreactive 6-keto-prostaglandin F1α, a stable metabolite of prostacyclin, in the rat.

2. The animals were fed on a potassium-deficient diet for 9 days. Twenty-four hour urine samples were collected daily for measurement of urinary excretion of immunoreactive 6-keto-PGF1α, PGE2 and 13,14-dihydro-15-keto-PGF2α (PGFM).

3. Hypokalaemia caused significant increases of the three prostaglandins measured.

4. We conclude that hypokalaemia is a potent stimulus of both renal and vascular prostaglandins. The results suggest that an increase in prostacyclin synthesis in peripheral blood vessel walls may be responsible for the resistance of blood pressure to infusion of pressor substances as well as for the normalcy of blood pressure, despite the presence of high circulating angiotensin II concentrations, in conditions associated with hypokalaemia.
The Ventilatory Effects of Doxapram in Normal Man
Authors: Calverley P. M. A. , Robson R. H. , Wraith P. K. , Prescott L. F. , Flenley D. C.
Published: August 2015

1. To determine the mode of action of doxapram in man we have measured ventilation, oxygen uptake, CO2 production, hypoxic and hypercapnic ventilatory responses in six healthy men before and during intravenous infusion to maintain a constant plasma level.

2. Doxapram changed neither resting oxygen uptake nor CO2 production but produced a substantial increase in resting ventilation at both levels of end-tidal CO2 studied.

3. Doxapram increased the ventilatory response to isocapnic hypoxia from − 0.8 ± 0.4 litre min−1 (%Sao2)−1 to −1.63 ± 0.9 litres min−1 (%Sao2)−1. This was similar to the increase in hypoxic sensitivity which resulted from raising the end-tidal CO2 by 0.5 kPa without adding doxapram.

4. The slope of the ventilatory response to rebreathing CO2 rose from 11.6 ± 5.3 litres min−1 kPa−1 to 20,4 ± 9.8 litres min−1 kPa−1 during doxapram infusion.

5. The marked increase in the ventilatory response to CO2 implies that doxapram has a central action, but the potentiation of the hypoxic drive also suggests that the drug acts on peripheral chemoreceptors, or upon their central connections, at therapeutic concentrations in normal unanaesthetized subjects.
Normal Adrenocortical Response to Adrenocorticotrophic Hormone in Patients with Homozygous Familial Hypercholesterolaemia
Authors: Allen J. M. , Thompson G. R. , Myant N. B.
Published: August 2015

1. Plasma cortisol concentration was measured in three subjects with homozygous familial hypercholesterolaemia immediately before, and 30 and 60 min after, an intramuscular injection of adrenocorticotrophic hormone. The baseline values and the values at 30 and 60 min were within the normal range.

2. We conclude that in the presence of a genetic deficiency of low-density lipoprotein receptors, the human adrenal cortex can respond to a single injection of adrenocorticotrophic hormone with a normal increase in corticosteroid production.
Plasma Catecholamines do Not Invariably Reflect Sympathetically Induced Changes in Blood Pressure in Man
Authors: Mancia G. , Ferrari A. , Gregorini Luisa , Leonetti G. , Parati G. , Picotti G. B. , Ravazzani Carla , Zanchetti A.
Published: August 2015

1. Plasma concentrations of noradrenaline and adrenaline were measured radioenzymatically in nine subjects during 4 min pressor and depressor responses (intra-arterial measurements) induced by increasing and reducing sympathetic vasoconstrictor tone via carotid baroreceptor deactivation and stimulation (neck chamber technique).

2. During the pressor response (15 ± 3 mmHg, mean ± se) plasma noradrenaline and adrenaline showed various changes in the different subjects and on average were not significantly increased above control. During the depressor response (−9 ± 2 mmHg) plasma noradrenaline and adrenaline also showed various changes in the subjects and were on average not significantly reduced below control.

3. In contrast the same subjects all showed an increase in noradrenaline and adrenaline (average 76 and 117%) at the fourth minute of a tilting manoeuvre with- a return to pretilting values no more than 4 min after resumption of the supine position.

4. These results suggest that the moderate and/or restricted alterations in sympathetic tone produced by manipulating a single baroreflex, though capable of affecting blood pressure, are not reflected by alterations in plasma catecholamines. To modify these humoral indices significantly, the more drastic or more diffuse alterations in sympathetic activity that may be produced by manipulating low as well as high pressure reflexogenic areas are needed.
Blood Pressure and Casual Urine Electrolytes in 93 London Factory Workers
Authors: Khaw Kay Tee
Published: August 2015

1. A survey of blood pressure in 93 male London factory workers found a significant correlation between individual systolic blood pressure and sodium/creatinine and sodium/potassium ratios estimated from casual urine samples.

2. Casual urine samples may have value in assessing the dynamic relationship between blood pressure and electrolytes.
Haemodynamic and Metabolic Effects of α-Adrenoceptor Blockade with Phentolamine at Rest and during Forearm Exercise
Authors: Hartling O. J. , Trap-Jensen J.
Published: August 2015

1. The pre- and post-junctional α-adrenoceptor blocking agent, phentolamine, was given by intravenous infusion to eight healthy volunteers during rest, forearm exercise and post-exercise.

2. Phentolamine produced a sustained increase in heart rate. The diastolic blood pressure decreased slightly whereas systolic and mean blood pressures remained unchanged. Phentolamine caused a marked increase in the forearm blood flow and a decrease in vascular resistance at rest and post-exercise, but did not influence the blood flow or vascular resistance in the exercising forearm.

3. There was a small increase in arterial blood glucose concentration, and a decrease in blood alanine concentration during drug infusion. Blood lactate was not affected by phentolamine. The arterial concentrations of free fatty acids and glycerol increased, and the concentration of triglycerides decreased during phentolamine infusion.

4. Forearm exchange of glucose, lactate, alanine, glycerol, free fatty acids, triglycerides and forearm oxygen consumption were not changed significantly.

5. These findings corroborate the concept that α-adrenoceptor induced vasoconstriction plays a subordinate role in exercising skeletal muscle. All of the metabolic findings might be explained as secondary to an increased noradrenaline release during phentolamine infusion.
The Dependence of Maximal Flow in Man on the Airway Gas Physical Properties
Authors: MacNee W. , Power J. , Innes A. , Douglas N. J. , Sudlow M. F.
Published: August 2015

1. The changes in maximum expiratory flow rates after washing out lung air with a helium/oxygen mixture (He/O2, 80: 20) were measured in 24 patients with chronic irreversible airflow obstruction (FEV1 1.77 ± sd 0.39 litres; FVC 3.62 ± 0.59 litres), and in six normal subjects. The percentage increase in flow breathing He/O2 was variable; however, it was similar in normal subjects and in patients with airflow obstruction, and in both groups decreased at low lung volumes. Contrary to previous studies, only three patients with chronic airflow obstruction failed consistently to increase flow rates by 20% when breathing He/O2 at all lung volumes measured.

2. In six normal subjects and 12 patients with chronic airflow obstruction airway gas viscosity was increased by breathing a neon/oxygen mixture (Ne/O2, 80:20). The response to Ne/O2 was again variable (normal subjects δVmax.40 4 ± sd 14%; patients δVmax.40 18 ±8%). Only two normal subjects and one patient with airflow obstruction consistently reduced their flow rates when breathing Ne/O2.

3. These results indicate either that there is no difference in the distribution of airflow resistance in normal subjects and in patients with chronic airflow obstruction, or that density as well as viscosity is an important determinant of flow in very small airways. In either case, He/O2 breathing is not a good discriminator of the site of airflow obstruction.
Mechanisms of Airway Narrowing in Acute Pulmonary Oedema in Dogs: Influence of the Vagus and Lung Volume
Authors: Chung K. F. , Keyes S. J. , Morgan B. M. , Jones P. W. , Snashall P. D.
Published: August 2015

1. In spontaneously breathing dogs (n = 8), maintained in the upright position, bronchial luminal diameter was measured from tantalum bronchograms. Changes in total intrathoracic lung volume were measured from radiographs taken at functional residual capacity (FRCR).

2. With cooling of the cervical vagi to 0–4°C mean bronchial diameter increased to 117 ±15 (sd)% of baseline diameter and FRCR increased to 113 ± 16 of baseline volumes respectively. There was a significant correlation between changes in FRCR and bronchial diameter.

3. After the vagi were rewarmed, pulmonary oedema was induced by rapid intravenous infusion of Hartmann's solution. Bronchi narrowed to a mean of 86 ± 9% of baseline calibre and FRCR decreased (mean = 95 ± 15%).

4. With vagotomy bronchial diameter increased (mean = 102 ± 12% of baseline diameter) but FRCR did not change significantly.

5. Excluding one dog with gross oedema, changes in bronchial diameter due to oedema correlated positively with changes in FRCR; after vagotomy the relationship between diameter and FRCR was similar to that seen after vagal cooling in the baseline state, though individual values were lower.

6. The shift in the diameter-FRCR relationship with vagotomy demonstrates that the direct bronchoconstrictor effect of the vagus is approximately doubled in the presence of pulmonary oedema.

7. Bronchial and peribronchial oedema does not appear to directly narrow the bronchial lumen.
A 45 000 Molecular Weight Human Renin Precursor is Synthesized in a Cell-Free Translation System
Authors: Parmentier Marc , Inagami Tadashi , Pochet Roland
Published: August 2015

1. Human kidney mRNA species were isolated and fractionated through a continuous sucrose gradient ultracentrifugation.

2. mRNA fractions were translated by using a rabbit reticulocyte lysate and [35S]metbionine as tracer. Double immunoprecipitation was carried out with highly specific anti-human renin and anti-rabbit γ-globulin antisera.

3. A 15S mRNA has been found to direct synthesis of a 45 000 molecular weight protein immunoprecipitable with anti-human renin. This protein is considered to be the ultimate precursor of renin (preprorenin).
Increased Excretion of Kallikrein during Dexamethasone Administrationl in Normal Man on Low and Normal Salt Intake
Authors: López José M. , Arteaga Eugenio , Rodriguez José A. , Croxatto Héctor
Published: August 2015

1. The effect of dexamethasone administration for 3 days on urinary kallikrein excretion was studied in 12 normal men with normal sodium intake (n=6) or low sodium intake (n=6). Urinary excretion of sodium, potassium, 17-hydroxycorticosteroids, aldosterone and water was also measured in all subjects.

2. Dexamethasone administration was associated with a significant increase in urinary kallikrein excretion (F3, 30 = 6.9; P < 0.001) regardless of sodium intake. No significant correlation could be established between the increase in urinary kallikrein excretion and changes in urinary sodium, potassium, 17-hydroxycorticosteroids, aldosterone or water.

3. These results suggest that dexamethasone can exert a direct action on the renal kallikrein-kinin system.