bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Sodium-Transport Inhibitors on Airway Smooth Muscle Contractility in Vitro
Authors: Knox Alan J. , Ajao Paul , Britton John R. , Tattersfield Anne E. 
Published: August 2015

1. To determine whether alterations in membrane sodium transport in airway smooth muscle can alter its contractility, we studied the effect of ouabain (a Na+/K+-adenosine triphosphatase inhibitor) and amiloride on contractile responses in bovine trachea and human bronchial rings in a series of studies.
2. Ouabain (10−6–10−4 mol/l) caused concentration-related contraction of bovine trachea with a maximum effect at 30 min; the mean increases in tension with 10−6, 10−5 and 10−4 mol/l ouabain were 19, 27, and 32%, respectively, of the maximum response seen with 10−3 mol/l histamine (n = 6). In human bronchial rings, ouabain (10−5 mol/l) caused a mean contraction which was 40% of the maximum response to methacholine (n = 8).
3. Calcium-free fluid (plus ethylenediaminetetra-acetic acid) and nifedipine (10−5 mol/l) inhibited ouabain-induced contractions, suggesting that contraction was mediated in part by calcium entry via voltage-dependent calcium channels. Phentolamine (10−5 mol/l) was without effect.
4. Ouabain (10−5 mol/l) did not alter histamine responsiveness in bovine trachea or methacholine responsiveness in human bronchial rings.
5. Amiloride did not affect resting tone in bovine trachea but caused a concentration-dependent relaxation of bovine tracheal strips preconstricted with carbachol, 10−3 mol/l amiloride relaxing strips completely over 15 minutes (n = 8). Pretreatment with amiloride significantly inhibited contraction produced by both histamine and carbachol in a dose-related manner, 10−5, 10−4 and 10−3 mol/l amiloride shifting the concentration of histamine producing 50% maximal contraction by 3-, 8- and 35-fold (n = 10) and that of carbachol by 1.4-, 6- and 86-fold (n = 8), respectively.
6. Amiloride also reduced the contraction produced by 10−4 mol/l ouabain from 32% (control) to 7% of the maximum histamine response.
7. Our results suggest that alterations in cell membrane sodium transport modify the contractile properties of airway smooth muscle.
Studies of the Porcine Intestinal Calcitriol Receptor in Pseudo-Vitamin D Deficiency Rickets Type I
Authors: Schröder B. , Kaune R. , Harmeyer J. 
Published: August 2015

1. Calcitriol (1,25-dihydroxyvitamin D3) concentrations in plasma of humans and pigs with pseudo-vitamin D deficiency rickets type I (PVDRI) have been reported to be significantly lower than in normal subjects and animals. Sometimes, however, calcitriol concentrations are relatively high in these subjects and animals (50–80 pmol/l) and nevertheless clinical symptoms of rickets develop. We have studied whether or not the development of rachitic lesions in piglets with PVDRI is due to altered binding properties of the intestinal calcitriol receptor in addition to the defective renal production of calcitriol. PVDRI piglets with clinical and biochemical symptoms of rickets (hypocalcaemia, increased activity of alkaline phosphatase) and with calcitriol concentrations in plasma of 83.7 ± 4.2 pmol/l (n = 7) were used. They were compared with unaffected piglets with normal calcitriol concentrations (178.0 ± 17.7 pmol/l, n = 9).
2. The equilibrium dissociation constant (Kd) of the receptor in the PVDRI piglets (0.31 ± 0.05 nmol/l) and in control piglets (0.33 ± 0.05 nmol/l) and the maximum binding capacity (Bmax.) (674 ± 103 and 719 ± 122 fmol/mg of protein, respectively) were not different (n = 9).
3. The association rate constant (kass) at 4°C [0.15 × 107 and 0.24 × 107 (mol/l)−1 min−1] and the dissociation rate constant (kdiss) (0.40 × 10−3 and 0.48 × 10−3 min−1; half-life of dissociation = 24.1 and 28.9 h, respectively) were also not different between diseased and control piglets.
4. No differences between PVDRI and control piglets were also found for the relative molecular mass (47 500 and 47700, respectively) and the Stokes' radius (3.04 and 3.05 nm, respectively) of the calcitriol receptor.
5. It is concluded that the intestinal calcitriol receptor of this animal model functions normally and that changes in binding properties and concentration of the intestinal calcitriol receptor do not contribute to the development of rachitic lesions in PVDRI piglets.
Stimulation of Active Renin Release in Normal and Hypertensive Pregnancy
Authors: Brown Mark A. , Zammit Vivienne C. , Adsett Delma 
Published: August 2015

1. Active plasma renin concentration but not total renin concentration is reduced in women with pregnancy-induced hypertension compared with normotensive pregnant women. This study was conducted to determine whether women with pregnancy-induced hypertension are able to stimulate release of active renin.
2. Active plasma renin concentration was measured as the generation of angiotensin I at physiological pH in the presence of excess renin substrate, and total renin concentration was determined in the same way after trypsin activation. Inactive plasma renin concentration was calculated as the difference between total renin and active plasma renin concentrations.
3. Resting active plasma renin concentration was significantly greater in third-trimester primigravidae compared with normotensive non-pregnant women and active plasma renin and total renin concentrations rose significantly without a fall in inactive plasma renin concentration in both groups after 2 h ambulation, suggesting increased release of active plasma renin and not conversion of circulating inactive to active renin. These responses were blunted in women taking oral contraceptives.
4. Although the active plasma renin concentration was significantly reduced in third-trimester primigravidae with pregnancy-induced hypertension, total renin concentration was not significantly different compared with normotensive women of similar gestation and in both groups 30 min 60° head-up tilt increased active but not inactive plasma renin concentration.
5. These studies show that in normal pregnancy active plasma renin concentration can be stimulated to a similar extent as in non-pregnant women, despite a higher resting level. This appears to be due to increased secretion of active plasma renin rather than conversion of circulating inactive to active renin. Women with pregnancy-induced hypertension are also still able to stimulate secretion of active renin despite resting concentrations similar to those of non-pregnant women. These data suggest that in pregnancy-induced hypertension basal secretion of active renin is prematurely reset to that in the non-pregnant state but that secretion of active renin responds normally to posture.
Blood Pressure, Heart Rate and Neuroendocrine Responses to a High Carbohydrate and a High Fat Meal in Healthy Young Subjects
Authors: Heseltine D. , Potter J. F. , Hartley G. , MacDonald I. A. , James O. F. W. 
Published: August 2015

1. The responses of blood pressure, heart rate, autonomic function and plasma insulin to a high carbohydrate and a high fat meal of equivalent energy value were studied in nine young volunteers.
2. Neither meal produced a significant change in supine or erect blood pressure. The high carbohydrate meal, however, resulted in an overall rise in both supine (6 beats/min) and erect (6 beats/min; P &lt; 0.05) heart rate, no such changes being seen after the high fat meal.
3. Plasma noradrenaline levels increased by a maximum of 126% at 90 min (0.98 to 2.22 nmol/l) after the high carbohydrate meal but were virtually unchanged after the high fat meal (P &lt; 0.01). Parasympathetic function showed no between-meal differences. Plasma insulin and glucose levels were significantly higher after the high carbohydrate meal than after the high fat meal. No postprandial difference in packed cell volume was found between meal types.
4. We conclude that, in young subjects, the postprandial blood pressure after a high carbohydrate meal is maintained by an increase in heart rate associated with increased sympathetic nervous system activity. These changes are at variance with the blood pressure and heart rate responses seen in the elderly after a high carbohydrate meal. A high fat meal has no significant cardiovascular or neuroendocrine effects in the young or old. The nutrient composition of meals has to be taken into account when studying the postprandial cardiovascular and neuroendocrine responses in the young.
Vascular Hypertrophy, Renin and Blood Pressure in the Young Spontaneously Hypertensive Rat
Authors: Morton James J. , Beattie Elisabeth C. , Griffin Sheila A. , MacPherson Fiona , Lyall Fiona , Russo Domenico 
Published: August 2015

1. Cardiovascular reactivity, blood vessel morphology, blood pressure and the activity of the renin—angiotensin system were determined in the 3-week-old spontaneously hypertensive (SHR), Wistar—Kyoto (WKY) and outbred Wistar (WIS) rat.
2. In an isolated perfused mesenteric artery preparation the SHR had a significantly increased maximum response to KCl and noradrenaline (P &lt; 0.02) compared with the WKY. Using a myograph, vascular structure was measured over a range of resistance arteries and showed a significant correlation between lumen diameter and both media cross-sectional area and thickness, with the regression line for the SHR shifted upwards indicating both increased media area and thickness. This was associated with a slight, but significant, narrowing of the lumen (P &lt; 0.01) and an increased media/lumen ratio (0.049 ±0.01, 0.034 ±0.007, 0.036 ±0.008 for SHR, WKY and WIS, respectively, means ±sd P &lt; 0.001). The SHR had a greater heart/body weight ratio than either the WKY or the WIS (P &lt; 0.001).
3. Both mesenteric artery and membrane protein content were higher in the SHR, indicating an increase in cell size or number.
4. Plasma renin activity (means ±sd) was lower in the SHR (1.0 ± 0.7 pmol of angiotensin I h−1 ml−1) than in the WKY (2.2±1.2 pmol of angiotensin I h−1 ml−1, P &lt; 0.001) but not different from that in the WIS (1.2±0.8 pmol of angiotensin I h−1 ml−1). Mesenteric artery vascular renin concentration was also lower in the SHR (P = 0.06). Plasma angiotensin II concentration (mean±sd) was similarly lower in the SHR (11.9 ±3.8 fmol/ml) than in the WKY (18.8 ± 6.2 fmol/ml, P &lt; 0.001) but not different from that in the WIS (14.5 ±5.8 fmol/ml). There was no difference in angiotensin II receptor number or affinity between the three rat strains.
5. Quiescent intra-arterial blood pressure was significantly higher in the SHR both 1 and 2 days after cannula insertion. On day 2 the pressure (mean ± sd) in the SHR was 112.7 ± 19.9 mmHg, in the WKY 81.1 ± 14.4 mmHg and in the WIS 75.1 ± 7.8 mmHg (P &lt; 0.001).
6. These data indicate the presence of marked vascular and cardiac hypertrophy in the SHR at a very early period in its development. Blood pressure is elevated and there is no overactivity of the renin system. We conclude that, at this time, there is no prehypertensive phase nor is there evidence of angiotensin II-mediated pressure-independent mechanism in the hypertrophic development.
Limits of brain tolerance to daily increments in serum sodium in chronically hyponatraemic rats treated with hypertonic saline or urea: advantages of urea
Authors: Soupart Alain , Stenuit Alain , Perier Olivier , Decaux Guy 
Published: August 2015

1. At present there is no consensus about the optimal management of hyponatraemia to prevent demyelinating brain lesions. We have evaluated in a large series of rats (n = 136) the protective role of urea for the brain in the treatment of severe chronic hyponatraemia. Urea (group I, n = 51) was compared with hypertonic saline in boluses (group II, n = 46) and with hypertonic saline in divided doses (group III, n = 39). Treatment was administered intraperitoneally over 48 h. The severity of brain lesions was assessed by histological scoring.
2. For 95% of the injured animals treated with hypertonic saline, brain lesions appeared for an absolute increment in serum Na+ concentration (δSNa+) of 20 mmol day−1 l−1. Above this limit neurological injuries gradually worsened, and beyond a transition zone (δSNa+ 20–23 mmol day−1 l−1) 89% (group III) to 100% (group II) of the animals were injured. This limit can be reached rapidly, as attested by the comparable severity of brain lesions observed in group II (mean δSNa+ 1 h after a bolus injection, 19 mmol/l) and in group III (mean δSNa+ 1 h after an injection, 2 mmol/l), both groups achieving similar daily δSNa+.
3. A correction above the threshold of 20 mmol day−1 l−1 is as toxic during the first 24 h as during the second day of the treatment. This can be deleterious even if a mildly hyponatraemic level (&gt;120 &lt;129 mmol/l) is achieved after 48 h. The maximum δSNa+ over 48 h tolerated by the brain can exceed 30 mmol/l (31−42 mmol/l), with a correction of serum Na+ concentration up to a normonatraemic level, provided that the successive daily δSNa+ was not greater than 20 mmol/l. The severity of the pre-existing hyponatraemia does not influence the outcome of the correction phase.
4. We have confirmed the protective effect of urea against the development of brain damage when used to correct hyponatraemia. The threshold of tolerance to daily δSNa+ after urea is identical to the limit defined for hypertonic saline, but a further rise in serum Na+ concentration (range of daily δSNa+ &gt;23 &gt;30 mmol/l) leads to a significantly lower incidence (47%, P &lt;0.01 compared with group II and P &lt;0.02 compared with group III) and severity (P &lt;0.03 compared with group II and P &lt;0.005 compared with group III) of neurological complications.
Na+/H+ antiport and buffering capacity in human polymorphonuclear and mononuclear leucocytes
Authors: Frighi V. , Ng L. L. , Lewis A. , Dhar H. 
Published: August 2015

1. Na+/H+ antiport activity was measured in peripheral blood polymorphonuclear and mononuclear cells of 12 healthy subjects by using an intracellular pH clamp technique to determine the external Na+-dependent H+ efflux rate in cells loaded with a pH-sensitive fluorescent dye, bis(carboxyethyl)carboxyfluorescein. The change in external Na+ concentrations for all pH measurements was similar in both cell types.
2. A significant difference between the two types of cells was found, the polymorphonuclear leucocytes having a higher Na+/H+ antiport activity than the lymphocytes. Cellular intrinsic buffering capacity measured in the absence of HCO−3 was also higher in the polymorphonuclear cells than in the lymphocytes.
3. These differences may be associated with a difference in the role of the Na+/H+ exchanger in these two types of cells, although in vivo the presence of HCO−3/Cl− exchangers may also contribute to intracellular pH homoeostasis.
The contribution of the large intestine to blood acetate in man
Authors: Scheppach W. , Pomare E. W. , Elia M. , Cummings J. H. 
Published: August 2015

1. To test the hypothesis that the colon contributes significantly to venous plasma acetate concentrations, experiments were carried out in healthy volunteers and ileostomy patients.
2. Fasting plasma acetate levels were measured in 10 ileostomy patients and compared with those in 21 control subjects. Values in ileostomy patients (21.3 ± 0.8 μmol/l) were significantly lower than in control subjects (48.0 ± 4.2 μmol/l).
3. Plasma acetate concentration was estimated in eight healthy volunteers during 108 h of continuous fasting. Acetate concentrations rose significantly from 12 h (43.9 ± 4.4 μmol/l) to 108 h of starvation (114.0 ± 15.6 μmol/l) and fell back to normal fasting values on refeeding and another 12 h fast (44.3 ± 4.7 μmol/l).
4. When colonic fermentation was stimulated after oral ingestion of 10 g of lactulose, the plasma acetate concentration increased significantly (from 44.0 ± 7.4 to 114.4 ± 16.2 μmol/l) in seven healthy control subjects. This rise was not affected by concomitant dosage of metronidazole.
5. These data suggest that there are at least two major sources of acetate in man, an endogenous source and the colon which probably becomes more important when fermentation of carbohydrate is occurring.
Transcription, storage and release of atrial natriuretic factor in the failing human heart
Authors: Fischer Thomas A. , Haass Markus , Dietz Rainer , Willenbrock Roland C. , Saggau Werner , Lang Rudolf E. , Kübler Wolfgang 
Published: August 2015

1. In this study the relationship between the synthesis of atrial natriuretic factor at the level of atrial natriuretic factor mRNA and the atrial storage and circulating plasma levels of atrial natriuretic factor were investigated in 15 patients with heart failure. The patients underwent right and left heart catheterization before cardiac surgery for valve replacement or coronary artery bypass grafting.
2. Plasma concentrations of atrial natriuretic factor were correlated to atrial levels of atrial natriuretic factor mRNA. Atrial levels of atrial natriuretic factor mRNA and plasma concentrations of atrial natriuretic factor exhibited a close correlation to both pulmonary artery pressure and left atrial pressure. No relationship, however, could be found between the right atrial content of atrial natriuretic factor and both the expression of atrial natriuretic factor mRNA in the atria and the plasma levels of atrial natriuretic factor.
3. From these data it may be concluded that increased plasma levels of atrial natriuretic factor in the pressure-and/or volume-overloaded heart are associated with an elevated level of atrial natriuretic factor mRNA. We suggest that not only plasma levels of atrial natriuretic factor but also the expression of atrial natriuretic factor in the atria are related to left ventricular filling pressures in the failing human heart.
Role of the wrist cuff in forearm plethysmography
Authors: Lenders Jacques , Janssen Geert-Jan , Smits Paul , Thien Theo 
Published: August 2015

1. To determine whether a wrist cuff is necessary to measure the forearm blood flow correctly, we studied the effects of wrist cuff inflation to supra-venous and supra-systolic pressure values over a large range of forearm blood flow values: in the basal state, during post-occlusive hyperaemia of the hand, and during heating of the hand with warm air. Eleven healthy men participated, and the study was carried out at two different ambient temperatures of 20 and 25°C.
2. In the basal state, the measured forearm blood flow was lowest with the wrist cuff at supra-systolic pressure. With the wrist cuff at supra-venous pressure the forearm blood flow was also lower than with an uninflated cuff, but only significantly so when the basal forearm blood flow was higher (at a room temperature of 25°C).
3. During post-occlusive hyperaemia, inflating the wrist cuff to supra-systolic pressure produced the lowest forearm blood flow value at both room temperatures. In addition, with the wrist cuff at supra-venous pressure, forearm blood flow values were lower than with the uninflated cuff, but the supra-venous cuff pressure was clearly less efficient in excluding the hand blood flow than the supra-systolic cuff pressure.
4. During heating of the hand, both supra-systolic and supra-venous cuff pressures were effective in excluding the hand blood flow at both room temperatures. The forearm blood flow measured with the wrist cuff at supra-systolic pressure was lower than that measured with the wrist cuff at supra-venous pressure, but the difference was only significant at a room temperature of 20°C.
5. In conclusion, we have demonstrated that a wrist cuff at supra-systolic pressure is most appropriate for the exclusion of the hand circulation in order to measure the forearm blood flow correctly.
Renal sensitivity to endothelium-derived-relaxing-factor-mediated vasodilatation in the spontaneously hypertensive rat
Authors: Burton G. A. , Haylor J. , de Jonge A. 
Published: August 2015

1. The sensitivity of the kidney to endothelium-derived-relaxing-factor-mediated vasodilatation has been investigated in the spontaneously hypertensive rat and the Wistar-Kyoto normotensive rat using an isolated perfused rat kidney model.
2. No difference in the slope, ED50 or maximum of the concentration-response curves for the endothelial-dependent vasodilators A23187, a calcium ionophore, and acetylcholine could be demonstrated between kidneys obtained from the spontaneously hypertensive and the Wistar-Kyoto normotensive rats.
3. No difference in the slope or the ED50 of the concentration-response curve for the endothelial-independent vasodilators, atrial natriuretic factor and sodium nitroprusside, could be demonstrated between kidneys obtained from the spontaneously hypertensive and the Wistar-Kyoto normotensive rats. However, in the spontaneously hypertensive rats, the maximum vasodilator response to atrial natriuretic factor, but not to sodium nitroprusside, was increased.
4. The perfused kidney from the spontaneously hypertensive rat also showed an increase in the maximum but not in the slope or ED50 of the concentration-response curve for vasoconstriction induced by the α1-adrenoceptor agonist methoxamine.
5. The involvement of endothelium-derived relaxing factor in mediating the renal vasodilator response to A23187 and acetylcholine was confirmed in experiments performed in perfused kidneys obtained from normotensive Wistar rats.
6. It is concluded that the sensitivity of the kidney to endothelium-derived-relaxing-factor-mediated vasodilatation is not modified in the spontaneously hypertensive rat. This does not, however, exclude a role for the synthesis of endothelium-derived relaxing factor in the maintenance of blood pressure in the spontaneously hypertensive rat.
Effects of treatment with nasal continuous positive airway pressure on atrial natriuretic peptide and arginine vasopressin release during sleep in patients with obstructive sleep apnoea
Authors: Krieger J. , Follenius M. , Sforza E. , Brandenberger G. , Peter J. D. 
Published: August 2015

1. Patients with obstructive sleep apnoea have increased diuresis during sleep, which decreases with nasal continuous positive airway pressure treatment. These changes have been attributed to an increased release of atrial natriuretic peptide in obstructive sleep apnoea, and its decrease with continuous positive airway pressure treatment.
2. In order to clarify the change in plasma atrial natriuretic peptide level and to investigate the underlying mechanisms, blood samples were taken at 10 min intervals from nine patients with obstructive sleep apnoea during two nights when the patients were either untreated or treated with continuous positive airway pressure. Polysomnographic monitoring, including transcutaneous oximetry, and measurement of oesophageal pressure were performed simultaneously. Plasma arginine vasopressin was also measured.
3. The plasma level of arginine vasopressin did not change. The level of atrial natriuretic peptide was high and exhibited secretion bursts in six out of the nine patients; it drastically decreased with continuous positive airway pressure treatment.
4. Across the patients, the mean plasma levels of atrial natriuretic peptide was correlated with the degree of hypoxaemia and the degree of oesophageal pressure swings during the sleep apnoeas.
5. Within the patients, cross-correlation studies suggested that the atrial natriuretic peptide secretory bursts were related either to the oesophageal pressure swings or to the apnoea-related hypoxaemia.
6. We conclude that release of atrial natriuretic peptide decreases with continuous positive airway pressure treatment in those patients with obstructive sleep apnoea who have increased release of atrial natriuretic peptide before treatment.
7. The results are in agreement with the hypothesis that the haemodynamic changes induced by the increased swings in intra-thoracic pressure during ineffective respiratory efforts or by the hypoxia-induced vasoconstriction play a role in these changes.