bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular Responses to Vasopressin Antagonists in Man and Rat
Authors: Burrell Louise M. , Phillips Paddy A. , Rolls K. A. , Buxton B. F. , Johnston C. I. , Liu J. J. 
Published: August 2015

1. The effects of the non-peptide arginine vasopressin V1 receptor antagonist (OPC-21268) and the non-peptide V2 receptor antagonist (OPC-31260) on vasopressin-induced contraction of human internal mammary arteries and rat mesenteric resistance arteries were investigated.
2. In human internal mammary arteries, the non-peptide V1 receptor antagonist, OPC-21268, failed to antagonize vasopressin-induced contraction at low concentrations and potentiated the contraction at higher concentrations (300 nmol/l, P &lt; 0.05). A peptide selective V1 receptor antagonist {[d(CH2)5, sarcosine7]arginine vasopressin} potently inhibited the vasopressin-induced contraction, indicating the presence of functionally constrictor V1 receptors in human internal mammary arteries. Both peptide (desGly-NH29[d(CH2)5, D-Ile2, Ile4]arginine vasopressin) and non-peptide ‘selective’ V2 receptor antagonists (OPC-31260, 3 μmol/l) significantly antagonized vasopressin-induced contraction (P &lt; 0.01), indicating partial V1 receptor antagonist activity.
3. The vasopressin-induced contraction in human internal mammary arteries was reversed by high concentrations of the non-peptide V2 receptor antagonist, OPC-31260, but not by the non-peptide V1 receptor antagonist, OPC-21268.
5. In rat mesenteric resistance arteries, both OPC-21268 (10 nmol/l) and OPC-31260 (1 μmol/l) antagonized vasopressin-induced contraction (P &lt; 0.01).
6. The results of this study in vitro indicate that in human internal mammary arteries, the non-peptide OPC-21268 is a partial V1 receptor agonist with no V1 receptor antagonist activity, whereas the non-peptide OPC-31260 acts as a V1 receptor antagonist. Both OPC-21268 and OPC-31260 have V1 receptor antagonistic activity in vitro in the rat mesenteric resistance arteries.
7. These findings illustrate the complexity of the vasopressin receptor system and highlight the variability in results with peptide or non-peptide vasopressin analogues, between studies in vivo or in vitro, between species and across vascular beds.
Insulin Sensitivity in Post-Obese Women
Authors: Toubro Søren , Western Philip , Bülow Jens , Macdonald Ian , Raben Anne , Christensen Niels Juel , Madsen Joop , Astrup Arne 
Published: August 2015

1. Both increased and decreased sensitivity to insulin has been proposed to precede the development of obesity. Therefore, insulin sensitivity was measured during a 2 h hyperinsulinaemia (100 m-units min−1 m−2) euglycaemic (4.5 mmol/l) glucose clamp combined with indirect calorimetry in nine weight-stable post-obese women and in nine matched control women preceded by 12 h fasting after 48 h on a standardized diet.
2. Both glucose disposal rate (post-obese women, 9.5 ± 2.2 mg min−1 kg−1, control women, 11.2 ± 1.4 mg min−1 kg−1, not significant) and glucose oxidation (3.6 ± 0.5 mg min−1 kg−1 versus 4.0 ± 0.7 mg min−1 kg−1, not significant) were similar in the two groups during the last 30 min of the clamp. Lipid oxidation also decreased similarly during the clamp in the post-obese women (from 30.4 ± 12 to 2.0 ± 7 J min−1 kg−1) and in the control women (from 33.6 ± 11 to 5.4 ± 8 J min−1 kg−1, not significant). Basal plasma concentrations of free fatty acids were similar, but at the end of the clamp free fatty acids were lower in the post-obese women than in the control women (139 ± 19 and 276 ± 48 μmol/l, P = 0.02).
3. We conclude that the insulin sensitivity of glucose metabolism is unaltered in the post-obese state. The study, however, points to an increased antilipolytic insulin action in post-obese subjects, which may favour fat storage and lower lipid oxidation rate post-prandially. The results suggest that alterations in lipid metabolism may contribute to the explanation of the propensity to obesity in susceptible individuals.
Cardiac Muscle Protein Gene Expression in the Endotoxin-Treated Rat
Authors: Macallan D. C. , Griffin G. E. 
Published: August 2015

1. Sepsis is associated with marked changes in cardiac muscle protein synthesis. Such changes may be the result of altered transcription of specific myofibrillar protein mRNAs.
2. In order to investigate myofibrillar protein gene expression, a rat model of sepsis was used. Adult rats were given a single sub-lethal dose of lipopolysaccharide by the intraperitoneal route. At various times thereafter, rats were killed and ventricular muscle was removed. RNA was extracted and transferred to nylon membranes. Changes in expression of mRNA for α- and β-myosin heavy chain, α-actin, cardiac troponin C and carbonic anhydrase III were detected by Northern hybridization.
3. After treatment with lipopolysaccharide, mRNA for β-myosin heavy chain increased to 260% of control values at 24 h and reached a maximum of 310% at 48 h. α-Myosin heavy chain mRNA levels fell to 72% of control values at 24 h. mRNA levels for α-actin, cardiac troponin C and carbonic anhydrase III remained unchanged.
4. In order to investigate the role of tumour necrosis factor-α in this process, some rats were pretreated with monoclonal antibody against tumour necrosis factor-α before receiving lipopolysaccharide. Such animals showed an absence of tumour necrosis factor-α bioactivity in plasma, but changes in myocardial protein mRNA levels were no different from those seen in animals receiving lipopolysaccharide alone.
5. The reduction in protein synthesis in cardiac muscle in sepsis does not appear to be the result of reduced expression of genes for structural or soluble muscle protein. Rather there is a paradoxical increase in β-myosin heavy chain expression, which may represent a protective mechanism. Tumour necrosis factor-α does not appear to be involved in the mediation of these changes.
Increased Serum Concentrations of Adhesion Molecules after Coronary Angioplasty
Authors: Kurz Robert W. , Graf Bernhard , Gremmel Franz , Wurnig Christian , Stockenhuber Felix 
Published: August 2015

1. Reocclusion is still a significant complication after percutaneous transluminal coronary angioplasty. The injury of coronary arteries resulting from PTCA plays an important role in the pathophysiology of both abrupt closure and late restenosis after an initially successful procedure. Cytokines play a pivotal role in the accumulation of circulating blood cells at the endothelium and are known to regulate their interaction with the vessel wall.
2. To obtain further information about this interaction, serum concentrations of soluble endothelial leukocyte adhesion molecule 1 (sELAM-1), leucocyte endothelial cell adhesion molecule 1 (sL-selectin), intercellular adhesion molecule 1 (sICAM-1), interleukin 2 receptor (sIL-2R) and interleukin 8 (IL-8) detected by enzyme-linked immunosorbent assay were monitored in 30 consecutive patients referred for elective PTCA. Fifteen patients who underwent elective coronary angiography without PTCA served as controls.
3. All patients underwent successful first PTCA. Within 24 h the serum concentrations of sELAM-1 increased gradually from 21.7 (SD 7.1) to 48.2 (SD 8.6) ng/ml (P &lt; 0.01); levels of sL-selectin rose from 982.1 (SD 128.7) to 1541.3 (SD 104.6) ng/ml after 48h (P &lt; 0.01). Serum levels of IL-8 remained stable initially, but peaked at the end of the observation time of 72 h (9.4, SD 3.8, versus 16.1, SD 4.9 ng/ml; P &lt; 0.05). A positive correlation was found between the number of dilatations and the rise in these parameters (P &lt; 0.01). No significant changes were found in the serum concentrations of sICAM-1 and sIL-2R after PTCA or in any of the parameters in patients after coronary angiography.
4. We conclude that PTCA induces a significant rise in the concentration of certain adhesion molecules in serum. Thus, we provide preliminary data on the potential role of cytokines for blood cell-endothelium interaction after PTCA. Further investigations and larger numbers of patients are needed to clarify the role of circulating cytokines for endothelial injury and restenosis after PTCA.
Low-Frequency Spontaneous Fluctuations of R-R Interval and Blood Pressure in Conscious Humans: A Baroreceptor or Central Phenomenon?
Authors: Bernardi Luciano , Leuzzi Stefano , Radaelli Alberto , Passino Claudio , Johnston James A. , Sleight Peter 
Published: August 2015

1. We have tested the hypothesis that the non-respiratory, low-frequency (around 0.1 Hz) fluctuations of heart rate variability are generated by the baroreflexes, but with a delay caused by the slower response of the efferent sympathetic arm, (compared with the vagus), in 11 healthy subjects (mean age ± SD 27 ± 5 years).
2. In random order, at the onset of 20 s of apnoea starting at end expiration, we applied either 600 ms neck suction (−40 mmHg) to the carotid sinus region, or no stimulus (anticipation control), or a loud whistle (alerting control), every 60s, for 30 min. (i.e. 10 of each ‘stimulus’). We recorded neck pressure, blood pressure (Finapres), R-R interval (ECG), infra-red plethysmographic skin blood flow and respiration (impedance). By subtracting the alerting response from the neck suction response we obtained the responses caused purely by baroreceptor stimulation.
3. The initial reflex bradycardia and hypotension was followed by arteriolar vasoconstriction, presumably due to recompensation by the baroreflex, and then by a further reflex bradycardia—producing a decaying oscillation of the R-R interval about the control R-R. The period of this damped oscillation was 0.103 ± 0.024 Hz, similar to the frequency of the low-frequency peak obtained by power spectral analysis of heart rate variability (0.093 ± 0.016 Hz, not significant) at rest. These two values were significantly correlated in individual subjects (r = 0.715, P &lt; 0.025).
4. These findings support the hypothesis that the low-frequency waves of heart rate variability can be generated from baroreceptor sensed blood pressure fluctuations.
Plasma Natriuretic Peptides and Cardiac Volume during Acute Changes in Intravascular Volume in Haemodialysis Patients
Authors: Corboy John C. , Walker Robert J. , Simmonds Mark B. , Wilkins Gerard T. , Richards A. Mark , Espiner Eric A. 
Published: August 2015

1. Plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptides (BNP) were measured, along with left and right atrial and left ventricular volumes, in eight patients with chronic renal failure before and after the removal of 2.1 ± 0.61 of fluid by ultrafiltration and again during volume repletion with intravenous sodium chloride solution (150 mmol/l saline) to restore body weight plus 0.5 kg.
2. Baseline levels of ANP (46.0 ± 7.5 pmol/l) and BNP (22.0 ± 4.4 pmol/l) were elevated above normal. There was a significant reduction in plasma ANP (26.5 ± 4.7 pmol/l, P &lt; 0.05) and BNP (19.1 ± 4.9 pmol/l, P &lt; 0.05)) following ultrafiltration. Changes in plasma ANP during ultrafiltration correlated significantly with changes in left atrial volume (r = 0.643, P &lt; 0.05).
3. During volume repletion there was an exaggerated release of ANP (mean level post repletion 71.3 ± 20.8 pmol/l) which was not paralleled by changes in BNP. Changes in BNP were small, showing no correlation with atrial or ventricular volumes during either ultrafiltration or volume repletion.
4. These findings indicate that in chronic renal failure without left ventricular dysfunction, moderate acute changes in volume status elict only small immediate responses in plasma BNP. Changes in plasma ANP are greater than BNP and more responsive to changes in left atrial volume.
Impaired Renal Function in Obstructive Jaundice: Enhanced Glomerular Thromboxane Synthesis and Effects of Thromboxane Receptor Blockade in Bile Duct-Ligated Rats
Authors: Kramer Herbert J. , Schwarting Kriemhild , Bäcker Angela 
Published: August 2015

1. Patients with obstructive jaundice are especially susceptible to acute renal failure. We have previously observed that in rats with bile duct ligation impaired renal function is associated with increased urinary thromboxane excretion.
2. In the present study we therefore investigated, in rats with bile duct ligation, renal function, urinary thromboxane excretion and thromboxane B2 synthesis by isolated glomeruli as well as the effects of the thromboxane A2/prostaglandin H2 receptor antagonist Daltroban on renal function in rats with bile duct ligation as compared with sham-operated rats.
3. On the fourth day after bile duct ligation (n = 7 rats) endogenous creatinine clearance as an estimate of glomerular filtration rate was significantly reduced to 0.74 ± 0.05 (SEM) as compared with 1.06 ± 0.09 ml min−1 g−1 kidney weight in sham-operated rats (n = 7, P &lt; 0.01). In rats with bile duct ligation, urine volume was slightly increased, whereas urinary sodium (Na+) (P &lt; 0.001) and potassium (K+) (P &lt; 0.01) excretion as well as urine osmolarity (P &lt; 0.05) were significantly reduced and lower than in sham-operated rats.
4. Urinary thromboxane excretion was significantly higher in rats with bile duct ligation than in sham-operated rats: 116.6 ± 22.3 versus 56.8 ± 10.2 pmol 24h−1 100 g−1 body weight (P &lt; 0.05). Thromboxane B2 synthesis in glomeruli isolated from rats with bile duct ligation was also significantly higher than in sham-operated rats: 12.6 ± 2.0 versus 6.4 ± 0.9 pmol h−1 mg−1 protein (P &lt; 0.05).
5. The thromboxane A2/prostaglandin H2 receptor antagonist Daltroban normalized glomerular filtration rate in a second group of rats with bile duct ligation (n = 7) to 1.03 ± 0.08 (P &lt; 0.01) and slightly increased it in sham-operated rats (n = 7) to 1.24 ± 0.11 ml min−1 g−1 kidney weight (not significant). Daltroban, while without effects on urine volume and osmolarity in sham-operated rats, further increased urine volume and decreased osmolarity in rats with bile duct ligation after surgery. After surgery Daltroban reduced fractional Na+ and K+ excretion in sham-operated rats and in rats with bile duct ligation.
6. The results suggest that obstructive jaundice following bile duct ligation is associated with enhanced renal glomerular thromboxane A2 synthesis, which suppresses glomerular filtration rate and predisposes to acute renal failure. Treatment with Daltroban, a specific thromboxane A2/prostaglandin H2 receptor antagonist, restores glomerular filtration rate to normal, probably secondary to normalization of disturbed intrarenal blood flow following bile duct ligation.
Comparative Effects of Atrial Natriuretic Peptide and Brain Natriuretic Peptide on the Aldosterone and Pressor Responses to Angiotensin Ii in Man
Authors: Cargill Robert I. , Struthers Allan D. , Lipworth Brian J. 
Published: August 2015

1. Atrial natriuretic peptide and brain natriuretic peptide have similar vasodilator and natriuretic properties, although little information is available regarding their relative effects as antagonists of the renin—angiotensin—aldosterone system. We have therefore compared how atrial natriuretic peptide and brain natriuretic peptide affect the systemic pressor and aldosterone responses to angiotensin II in eight male subjects.
2. Each subject was studied on three separate occasions, when they received a 60-min infusion of placebo, atrial natriuretic peptide (10 pmol min−1 kg−1) or brain natriuretic peptide (10 pmolmin−1 kg−1), with a concomitant infusion of angiotensin II (6 ng min−1 kg−1) given for the final 30 min of the infusion period. The change in haemodynamic parameters and plasma aldosterone induced by angiotensin II was measured. Plasma concentrations of atrial natriuretic peptide (182 ± 23 pmol/l) and brain natriuretic peptide (193 ± 25 pmol/l) achieved at steady-state during the infusion on each study day were not significantly different.
3. Increases in mean arterial pressure in response to angiotensin II were significantly lowered by concomitant infusion of atrial natriuretic peptide (21.0 ± 1.7 mmHg) and brain natriuretic peptide (20.1 ± 1.9 mmHg) compared with placebo (29.0 ± 4.1 mmHg). There were similar effects on systolic and diastolic blood pressure. Cardiac output was decreased on each study day to the same extent by angiotensin II infusion. Total systemic vascular resistance showed a non-significant trend towards an attenuated response to angiotensin II when atrial natriuretic peptide or brain natriuretic peptide was infused concomitantly in comparison with placebo.
4. Plasma aldosterone increased by 326 ± 49 pmol/l when angiotensin II was infused with placebo. Both atrial natriuretic peptide and brain natriuretic peptide significantly blunted this response, although the increase with atrial natriuretic peptide (19 ± 35 pmol/l) was significantly lower than the increase with brain natriuretic peptide (133 ± 19 pmol/l).
5. Atrial natriuretic peptide and brain natriuretic peptide were therefore equally effective in blunting the systemic pressor response to angiotensin II. It was apparent, however, in view of similar plasma concentrations at steady state, that on a molar basis atrial natriuretic peptide was a more potent inhibitor of angiotensin II-induced aldosterone secretion than brain natriuretic peptide. These results suggest a dissociation between the haemodynamic and hormonal effects of atrial natriuretic peptide and brain natriuretic peptide in terms of antagonism of the renin—angiotensin—aldosterone system.
Inhibition of Acetylcholinesterase Selectively Potentiates NG-Monomethyl-l-Arginine-Resistant Actions of Acetylcholine in Human Forearm Vasculature
Authors: Chowienczyk P. J. , Cockcroft J. R. , Ritter J. M. 
Published: August 2015

1. NG-monomethyl-l-arginine (l-NMMA, a nitric oxide synthase inhibitor) inhibits vasodilator responses to acetylcholine but not methacholine in human forearm vasculature. To investigate whether this difference results from the relative susceptibility of these agonists to hydrolysis by acetylcholinesterase, we studied vasodilator responses to brachial artery administration of acetylcholine alone and in the presence of the acetylcholinesterase inhibitor edrophonium.
2. Vasodilator responses to constant-rate brachial artery infusions of acetylcholine were biphasic, with an initial peak response fading over 2 min to a plateau. Fade [(peak—plateau)/peak × 100%] was dose dependent (P &lt; 0.02), ranging from 43 ± 7% (mean ± SEM) at low dose (16 nmol/min) to 9 ± 8% at high dose (83 nmol/min).
3. Edrophonium (0.5 μmol/min intra-arterially) alone produced no change in forearm blood flow but increased blood flow responses to acetylcholine (P &lt; 0.01), causing an approximately 10-fold reduction in the dose required to increase plateau blood flow by 10 ml min−1 100 ml−1.
4. Responses to low doses of acetylcholine alone (16 and 41 nmol/min) faded more (P &lt; 0.01) than those to doses of acetylcholine with edrophonium chosen to produce similar plateau blood flows. Responses to acetylcholine (41 nmol/min) also faded more (P &lt; 0.01) than those to methacholine (5 nmol/min), producing matched plateau flows.
5. Peak and plateau responses to acetylcholine (41 nmol/min) were reduced (P &lt; 0.01) by similar amounts (47 ± 15% and 37 ± 13% respectively, P = 0.39) by coinfusion of l-NMMA (4 μmol/min). l-NMMA inhibited responses to acetylcholine more than matched responses to acetylcholine with edrophonium (P &lt; 0.01).
6. These results suggest that the actions of acetylcholine in human forearm resistance vessels are mediated both through an l-NMMA-sensitive pathway (l-arginine/nitric oxide pathway) that exhibits biphasic characteristics and through an l-NMMA-resistant pathway. The l-NMMA-resistant pathway is selectively potentiated by edrophonium. Inhibition of acetylcholinesterase by edrophonium may increase concentrations of acetylcholine deep to the endothelium and favour NO-independent actions on smooth muscle or sensory nerve endings mediating vasodilatation.
Serum and Platelet-Derived Growth Factor-Induced Expression of Vascular Permeability Factor Mrna by Human Vascular Smooth Muscle Cells In Vitro
Authors: Williams Bryan , Quinn-Baker Anne , Gallacher Barbara 
Published: August 2015

1. Endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation are key events in the pathogenesis of atherosclerosis. Vascular permeability factor (VPF), an endothelial-cell-specific multifunctional cytokine, was recently described, and has the potential to contribute to the development of endothelial dysfunction. The present study determines whether cultured human VSMCs express mRNA for VPF and whether VPF mRNA expression is influenced by human VSMC proliferation.
2. A 204 bp cDNA fragment, specific for all known variants of VPF mRNA, was cloned and used to demonstrate that human VSMCs express abundant quantities of VPF mRNA, whereas human endothelial cells do not. VPF mRNA levels were markedly diminished in non-proliferating human VSMCs. In contrast, when human VSMCs were stimulated to proliferate by exposure to serum, there was a rapid 6.6-fold increase (&lt;P &lt; 0.01 versus time 0 h) in VPF mRNA expression, which was maximal at 3 h and persisted beyond 24 h. The magnitude of the VPF mRNA response in human VSMCs was dependent on the serum concentration.
3. Platelet-derived growth factor also increased VPF mRNA expression by human VSMCs, thus confirming that recognized growth factors for VSMCs also potently influence the VPF gene.
4. In conclusion, VPF mRNA is expressed by human VSMCs, the magnitude of VPF expression being temporally related to the proliferation of human VSMCs and the potency of the growth-promoting stimulus. We propose that VPF produced by proliferating human VSMCs could act as a paracrine hormone to powerfully influence the permeability and growth of the overlying vascular endothelium. We thus report a novel mechanism whereby the stimulation of VSMC proliferation could potently and directly contribute to the development of endothelial dysfunction and the pathogenesis of vascular disease.
Effects of Inhaled Nebulized Morphine on Ventilation and Breathlessness during Exercise in Healthy Man
Authors: Masood A. R. , Subhan M. M. F. , Reed J. W. , Thomas S. H. L. 
Published: August 2015

1. Nebulized inhaled morphine has been reported to increase exercise endurance in patients with chronic lung disease and to relieve dyspnoea in patients with malignant disease. Potential mechanisms include a central effect occurring after systemic drug absorption or a local action mediated by receptors in the lung.
2. The ventilatory effects of nebulized morphine (10 and 25 mg) were therefore compared with those of intravenous morphine (1.0 and 2.5 mg) and placebo in a double-blind study involving 12 young healthy males. Submaximal cycle ergometry with respiratory gas analysis was performed 15 min after drug administration and breathlessness assessed using a linear visual analogue scale.
3. Neither dose of inhaled morphine had statistically significant effects on spirometry, heart rate, ventilation, respiratory gases or breathlessness at any level of exercise. The slopes and intercepts of the lines relating ventilation to breathlessness were also unaffected.
4. Intravenous morphine 2.5 mg reduced breathlessness slightly at the highest equivalent workload [mean (least significant range) 33 mm (26–40 mm)] compared with placebo [41 mm (34–48 mm), P &lt; 0.05] but had no other significant effects.
5. These results do not support the hypothesis that intrapulmonary opiate receptors modulate the sensation of breathlessness in healthy man. The possibility that inhaled morphine may affect breathlessness caused by other factors, such as disease, has not been excluded.