bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heart–Lung Interactions: The Sigh And Autonomic Control In The Bronchial And Coronary Circulations
Authors: Porges William L , Hennessy Edward J , Quail Anthony W , Cottee David BF , Moore Peter G , McIlveen Stephen A , Parsons Gibbe H , White Saxon W 
Published: March 2003

SUMMARY1. The Darwin hypothesis that human and animal expressions of emotion are the product of evolution and are tied to patterns of autonomic activity specified to progress the emotion remains under challenge.2. The sigh is a respiratory behaviour linked with emotional expression in animals and humans from birth to death. The aim of the present study was to explore Darwin’s hypothesis with respect to tied autonomic activity underlying sigh‐induced changes in the bronchial and coronary circulations.3. Awake dogs were prepared using pulsed ultrasonic flow probes on the right bronchial artery, parent intercostal artery and brachial artery, or on the right, circumflex and anterior descending coronary arteries. Central venous (CVP) and arterial pressures (AP) were measured; heart rate and flow conductances were derived. Three spontaneous sighs were monitored before and during random blockade of individual and combinations of cholinoceptors, α‐adrenoceptors and β‐adrenoceptors using methscopolamine, phentolamine and propranolol infusions. The data were subject to a 2
3 factorial analysis.4. A spontaneous sigh is marked by a transient fall and return (< 3 s) in CVP of 18 mmHg (from 4±1 to –14±2 mmHg), usually followed by apnoea lasting 23±2 s. There is an immediate tachycardia and small rise in AP (phase 1) then, during apnoea, bradycardia and a fall in AP (phase 2). During phase 2, bronchial and coronary blood flow and conductance rise two‐ to three‐fold over 30 s (peak at 8 s). The vascular changes are absent in parent intercostal and brachial beds.5. The phase 1 tachycardia is entirely cholino/adrenoceptor in origin and is due to cholinoceptor withdrawal and positive β‐adrenoceptor plus β‐adrenoceptor/cholinoceptor interaction activity, in the ratio 1.75 : 1. The phase 2 bradycardia is entirely cholinoceptor. However, only 17% of the peak rise in bronchial conductance is due to α‐/β‐adrenoceptor interactions (sympathetic withdrawal); 83% is due to non‐cholino/adrenoceptor mechanisms. In a separate four animals, the total sigh‐induced conductance rise is virtually abolished by prior infusion of NG‐nitro‐
L‐arginine methyl ester.6. Therefore, the mechanism of the sigh‐induced bronchial and conductance effects may be an efferent nitrergic component of an arterial chemoreceptor reflex induction of sighing. An alternative hypothesis invokes local stretch‐sensitive C‐fibre sensory nerve endings releasing substance P–calcitonin gene‐related peptide–neurokinin A in response to cardiovascular distortion secondary to the sudden transmural pressure rise when intrapleural pressure falls. Whatever the case, these effects and the cholino/adrenoceptor base for the heart rate and broncho/coronary changes support the Darwin hypothesis.
Bronchovascular Role In Pulmonary Congestion
Authors: McIlveen SA 
Published: March 2003

SUMMARY1. A postulated role for the bronchial circulation in the development of pulmonary congestion may be based on recent studies of bronchovascular control.2. The bronchial circulation is the nutrient blood supply of the conducting airways and, therefore, plays an important role in the function of the bronchial mucosa. Mucosal swelling secondary to elevation of mucosal capillary hydrostatic pressure may decrease airway calibre, increase resistance to airflow and precipitate symptoms of pulmonary congestion.3. Resting mucosal capillary hydrostatic pressure is relatively constant due to autoregulation of bronchial blood flow and is maintained low by nett bronchovascular constriction due to the dominance of autonomic vasoconstriction over nitric oxide‐dependent vasodilatation.4. Bronchial blood flow is also regulated by cardiac afferent reflexes. Stimulation of cardiac vagal and spinal afferents produces vasodilatation and vasoconstriction, respectively. Tonic activity of cardiac spinal afferents probably contributes to the resting autonomic vasoconstriction.5. Therefore, mild heart failure, which is associated with abnormal cardiovascular reflex function, may decrease cardiac spinal afferent‐mediated bronchial vasoconstriction and produce active dilatation due to stimulation of cardiac vagal afferents by excessive myocardial stretch, leading to bronchial mucosal swelling and pulmonary congestion.
In Situ Generation Of Nitric Oxide By Myenteric Neurons But Not By Mononuclear Cells Of The Human Colon
Authors: Tomobuchi Motoi , Oshitani Nobuhide , Matsumoto Takayuki , Kitano Atsuo , Seki Shuichi , Arakawa Tetsuo 
Published: March 2003

SUMMARY1. Production of nitric oxide (NO) is implicated in the pathogenesis of inflammatory bowel disease. However, the cells responsible for the production of NO in situ in the human colon remain unknown.2. Surgical samples from 12 patients with ulcerative colitis, eight patients with Crohn’s disease and 10 controls were studied. Possible generation of NO was visualized by reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity in human colon. Immunohistological staining for various NO synthase (NOS) isoforms (endothelial, neuronal and inducible), nitrotyrosine and interleukin‐2 was also performed.3. Reduced NADPH diaphorase activity was not found in lamina propria mononuclear cells, but was found in colonic epithelium, endothelium and myenteric neurons and their processes.4. The NADPH‐diaphorase activity positive processes were significantly less common in colon from patients with Crohn’s disease compared with control colon.5. Endothelial NOS was constitutively expressed on colonic endothelium.6. Neuronal NOS was constitutively expressed on myenteric neurons.7. Expression of inducible NOS (iNOS) was increased in the epithelium and endothelium of the colon of patients with ulcerative colitis.8. No correlation was found between expression of iNOS and NADPH diaphorase activity.9. Nitrotyrosine was expressed by lamina propria leucocytes, but not by epithelium.10. Interleukin‐2 was expressed on both leucocytes and myenteric neurons.11. Colonic epithelium, endothelium and myenteric neurons synthesize NO. Myenteric neurons were principally responsible for NO production and NO may act as a neurotransmitter in the enteric nervous system.
Association Of Serum Tumour Necrosis Factor‐α With Serum Low‐Density Lipoprotein–Cholesterol And Blood Pressure In Apparently Healthy Japanese Women
Authors: Ito Hiroyuki , Ohshima Akiko , Tsuzuki Misako , Ohto Naoko , Takao Kaoru , Hijii Chiga , Yanagawa Mami , Ogasawara Masashi , Nishioka Kazuo 
Published: March 2003

SUMMARY1. The pro‐inflammatory cytokine tumour necrosis factor (TNF)‐α is considered to be involved in the development of atherosclerosis by inducing local inflammatory responses in the vascular wall. Because TNF‐α is also known to affect lipid and glucose metabolism, the association between the circulating concentration of TNF‐α and atherogenic risk factors was examined in 82 apparently healthy Japanese women (aged 19–69 years; mean age 48.5 years).2. The mean (±SD) serum TNF‐α concentration was 2.7±0.9 pg/mL (range 1.4–5.9 pg/mL). The TNF‐α concentration showed significant correlations with age (r = 0.28; P = 0.01), body mass index (r = 0.27; P = 0.01), the waist–hip ratio (r = 0.41; P = 0.0002), percentage body fat (r = 0.30; P = 0.006), systolic (r = 0.32; P = 0.004) and diastolic (r = 0.24; P = 0.03) blood pressure, total cholesterol (r = 0.27; P = 0.02) and low‐ density lipoprotein–cholesterol (LDL‐C; r = 0.36; P = 0.001), while the correlations with high‐density lipoprotein–cholesterol (r = –0.20; P = 0.08) and insulin resistance estimated by the homeostasis model assessment (HOMAIR; r = 0.16; P = 0.15) were not statistically significant.3. When adjusted for age and menopause, TNF‐α was significantly associated with systolic blood pressure (r = 0.25; P = 0.02) and LDL‐C (r = 0.27; P = 0.02). The association between TNF‐α and LDL‐C remained significant when adjustment was made for age, menopause and the waist–hip ratio (r = 0.24; P = 0.03).4. Our results indicate that TNF‐α may play a role in modulating blood pressure and LDL‐C.
Structure‐Specific Membrane‐Fluidizing Effect Of Propofol
Authors: Tsuchiya H 
Published: March 2003

SUMMARY1. While recent studies about the pharmacological mechanism of the intravenous anaesthetic propofol (2,6‐diisopropylphenol) have focused on its interaction with functional proteins, there is the possibility that propofol alters membrane properties to produce anaesthesia. In the present study, the structure‐specific effects of propofol on liposomal model membranes were studied.2. The effect of propofol on the phase transition of membrane phospholipid was analysed spectrophotometrically using 1,2‐dipalmitoyl‐L‐α‐phosphatidylcholine liposomes. Propofol (50–200 μmol/L) lowered the phase transition temperature to fluidize membranes.3. Membrane fluidization was also analysed by measuring fluorescence polarization of liposomes consisting of 1,2‐ dipalmitoyl‐L‐α‐phosphatidylcholine, 1‐palmitoyl‐2‐oleoyl‐L‐ α‐phosphatidylcholine and cholesterol with different probes. Propofol fluidized all liposomal membranes in the concentration range 5–500 μmol/L by acting on both the inner and outer layers of the membranes.4. The membrane effects of propofol were compared with those of 2,6‐dialkylphenols, 1,3‐dialkylbenzenes, 2‐alkylphenols and alkylbenzenes. Although the membrane‐fluidizing effects were shared by a series of structural analogues, propofol was most effective in fluidizing membranes, especially liposomal membranes consisting of 20 mol% cholesterol and 80 mol% 1‐palmitoyl‐2‐oleoyl‐L‐α‐phosphatidylcholine.5. Lipophilicity was compared between propofol and its structural analogues using their capacity factors, determined by reverse‐phase high‐performance liquid chromatography. The potency of propofol to fluidize membranes was much greater than anticipated from its lipophilicity.6. At 0.125–1.0 μmol/L, almost corresponding to clinically relevant concentrations, propofol significantly enhanced membrane fluidity of cholesterol‐containing 1‐palmitoyl‐2‐oleoyl‐L‐α‐phosphatidylcholine liposomes.7. These results indicate that propofol fluidizes membranes in a structure‐specific manner through an interaction with membrane lipids. Such a membrane effect may be responsible for the mode of anaesthetic action of propofol.
Effect Of Metabolic Control On Nitrite And Nitrate Metabolism In Type 2 Diabetic Patients
Authors: Francesconi Federica , Mingardi Roberto , DeKreutzenberg Saula , Avogaro Angelo 
Published: March 2003

SUMMARY1. The measurement of nitrite and nitrate levels in plasma and urine is an approach to assess the activity of the endogenous nitric oxide (NO) system. The aim of the present study was to evaluate whether metabolic control may affect plasma levels and urinary excretion of nitrates and nitrites in type 2 diabetic patients.2. Twenty consecutive type 2 diabetic patients were studied twice: first (study 1), under poor metabolic control; and, second, after improved metabolic conditions. Determinations of the main metabolic parameters and of plasma nitrates and nitrites (NOX) were performed in the fasting state. A 24 h urinary specimen was obtained for glycosuria, NOX and creatinine. Diet compliance and home blood glucose monitoring was evaluated on a weekly basis until study 2 was performed after 32 ± 7 days: then, an identical protocol was repeated (study 2).3. Fasting plasma glucose was lower in study 2 (8.27 ± 2.11 vs 10.77 ± 3.88 mmol/L, respectively; P < 0.05); similarly glycosylated haemoglobin (HbA1c) improved significantly. Plasma NOX levels were similar between the first and second studies (14.3 ± 7.8 vs 13.5 ± 8.1 μmol/L, respectively); nor were any differences observed in urinary NOX excretion rates (726 ± 607 vs 689 ± 444 μmol/day, respectively). The urinary excretion fraction of NOX was higher during study 1 than during study 2 (3.22 ± 2.38 vs 1.88 ± 1.98%, respectively; P = 0.031). A relationship was observed between fasting plasma glucose levels and the urinary excretion fraction of NOX (r2 = 0.12; P = 0.026).4. In type 2 diabetic patients, plasma and urinary levels of NOX do not change after improvement of metabolic control. A worse metabolic control is associated with an increased urinary fraction excretion of NOX: thus, changes in plasma NOX concentration may reflect the effect of hyperglycaemia in the renal handling of these compounds rather than the effects on the L‐arginine–NO pathway.
Circumventricular Organs: Gateways to the Brain Subcellular Mechanisms Of Area Postrema Activation
Authors: Hay Meredith 
Published: March 2003

SUMMARY1. The present paper reviews some of the recent studies regarding the cellular mechanims regulating area postrema (AP) neuronal activity.2. The calcium currents involved in activation and regulation of AP neuronal activity most likely belong to the Q‐ and R‐family of calcium channels.3. Angiotensin II increases AP activity by facilitating inward calcium currents and inhibiting calcium‐activated potassium currents.4. The heterogeneity observed regarding responsiveness to glutamate and 5‐hydroxytryptamine and peptides may reflect multiple populations of AP neurons, each with specific roles in the integration of afferent and peptidergic neurotransmission.
Circumventricular Organs: Gateways to the Brain Role Of Circumventricular Organs In Pro‐Inflammatory Cytokine‐Induced Activation Of The Hypothalamic– Pituitary–Adrenal Axis
Authors: Buller Kathryn M 
Published: March 2003

SUMMARY1. The past 15 years has seen the emergence of a new field of neuroscience research based primarily on how the immune system and the central nervous system can interact. A notable example of this interaction occurs when peripheral inflammation, infection or tissue injury activates the hypothalamic– pituitary–adrenal axis (HPA).2. During such assaults, immune cells release the pro‐ inflammatory cytokines interleukin (IL)‐1, IL‐6 and tumour necrosis factor‐α into the general circulation.3. These cytokines are believed to act as mediators for HPA axis activation. However, physical limitations of cytokines impede their movement across the blood–brain barrier and, consequently, it has been unclear as to precisely how and where IL‐1β signals cross into the brain to trigger HPA axis activation.4. Evidence from recent anatomical and functional studies suggests two neuronal networks may be involved in triggering HPA axis activity in response to circulating cytokines. These are catecholamine cells of the medulla oblongata and the circumventricular organs (CVO).5. The present paper examines the role of CVO in generating HPA axis responses to pro‐inflammatory cytokines and culminates with a proposed model based on cytokine signalling primarily involving the area postrema and catecholamine cells in the ventrolateral and dorsal medulla.
Rigor Force Responses Of Permeabilized Fibres From Fast And Slow Skeletal Muscles Of Aged Rats
Authors: Plant David R , Lynch Gordon S 
Published: March 2003

SUMMARY1. Ageing is generally associated with a decline in skeletal muscle mass and strength and a slowing of muscle contraction, factors that impact upon the quality of life for the elderly. The mechanisms underlying this age‐related muscle weakness have not been fully resolved. The purpose of the present study was to determine whether the decrease in muscle force as a consequence of age could be attributed partly to a decrease in the number of cross‐bridges participating during contraction.2. Given that the rigor force is proportional to the approximate total number of interacting sites between the actin and myosin filaments, we tested the null hypothesis that the rigor force of permeabilized muscle fibres from young and old rats would not be different.3. Permeabilized fibres from the extensor digitorum longus (fast‐twitch; EDL) and soleus (predominantly slow‐twitch) muscles of young (6 months of age) and old (27 months of age) male F344 rats were activated in Ca2+‐buffered solutions to determine force–pCa characteristics (where pCa = –log10[Ca2+]) and then in solutions lacking ATP and Ca2+ to determine rigor force levels.4. The rigor forces for EDL and soleus muscle fibres were not different between young and old rats, indicating that the approximate total number of cross‐bridges that can be formed between filaments did not decline with age. We conclude that the age‐related decrease in force output is more likely attributed to a decrease in the force per cross‐bridge and/or decreases in the efficiency of excitation–contraction coupling.
Metalloendopeptidases EC 3.4.24.15 and EC 3.4.24.16 And Bradykinin B2 Receptors Do Not Play Important Roles In Renal Wrap Hypertension In Rabbits
Authors: Norman M Ursula , Lew Rebecca A , Smith A Ian , Denton Kate M , Evans Roger G 
Published: March 2003

SUMMARY1. The aim of the present study was to determine the effects of the metalloendopeptidase (EP) 24.15 and 24.16 inhibitor N‐[1‐(R,S)‐carboxy‐3‐phenylpropyl]‐Ala‐Aib‐Tyr‐p‐aminobenzoate (JA‐2) on haemodynamics and renal function in conscious rabbits with two‐kidney, two‐wrapped hypertension. We have also examined the role of endogenous bradykinin in the maintenance phase of this form of renovascular hypertension and whether inhibition of bradykinin degradation contributes to any potential effects of JA‐2.2. In two preliminary operations, rabbits were equipped with transit‐time ultrasound flow probes for measuring cardiac output (CO) and renal blood flow (RBF) and had both kidneys wrapped in cellophane. Starting 4 weeks after the last operation, rabbits underwent four studies (3–5 days apart), during which they were treated with combinations of the bradykinin B2 receptor antagonist icatibant or its vehicle (1 mL/kg bodyweight 0.9% w/v NaCl) and JA‐2 or its vehicle (1 mL/kg of a 5% w/v 2‐hydroxypropyl‐β‐cyclodextrin, 2.5% v/v dimethylsulphoxide solution). Renal function was monitored using standard renal clearance methods.3. Icatibant (10 μg/kg) had no significant effects on systemic haemodynamic variables (mean arterial pressure, heart rate or CO), renal haemodynamic variables (RBF or glomerular filtration rate), urine flow or sodium excretion. At 5 mg/kg plus 3 mg/kg per h, JA‐2 also did not affect any of these variables, either after icatibant vehicle treatment or after icatibant treatment.4. Our data do not support major roles for endogenous bradykinin or bradykinin degradation by EP 24.15/24.16 in the control of systemic and renal haemodynamics or renal excretory function in two‐kidney, two‐wrapped hypertension in rabbits.
Inflammation As A Key Event In The Development Of Neointima Following Vascular Balloon Injury
Authors: Wainwright Cl , Miller Am , Wadsworth Rm 
Published: March 2003

SUMMARY1. The present review discusses the current evidence to implicate leucocytes as key players in the development of neointima in arteries that have been subjected to balloon angioplasty injury.2. There is substantial clinical evidence that leucocytes are activated after angioplasty, as determined by increased plasma levels of both leucocyte granulation products and soluble leucocyte and endothelial cell adhesion molecules.3. Experimental evidence to implicate leucocytes in neointimal formation comes from studies that demonstrate leucocyte accumulation occurs within the vascular wall soon after injury and that induction of leukopenia prevents neointimal formation.4. The evidence implicating specific adhesion molecules and cytokines in the key events leading to neointimal formation is discussed.
Blood Pressure Lowering In Diabetes: A Brief Review Of The Current Evidence And Description Of A New Trial
Authors: Patel Anushka , Chalmers John , Neal Bruce , Chapman Neil , Girgis Seham , MacMahon Stephen 
Published: March 2003

SUMMARY1. Diabetes is a major global public health problem. The prevalence of this disease is predicted to increase sharply in the coming decades, particularly in less‐developed regions of the world.2. Most premature morbidity and mortality associated with diabetes relates to markedly increased risks of major cardiovascular diseases, such as myocardial infarction and stroke (macrovascular events), as well as microvascular complications, such as nephropathy and retinopathy.3. Hypertension is a prevalent and important risk factor for vascular events in these patients. However, observational data demonstrate a continuous relationship between blood pressure and risk of vascular events, suggesting that even those individuals considered normotensive may benefit from blood pressure lowering.4. Trials of blood pressure lowering among mostly hypertensive individuals with diabetes have demonstrated benefit of intervention on macrovascular and microvascular outcomes. Recent data may suggest additional effects of angiotensin‐ converting enzyme inhibitors independent of blood pressure lowering.5. Issues where data are lacking with respect to blood pressure lowering in diabetes include the effects of blood pressure lowering among non‐hypertensive individuals and the effects of blood pressure lowering regimens based on different classes of drug.6. Data expected to address some of these issues are being collected. These include a prospective meta‐analysis of blood pressure‐lowering trials with large numbers of patients with diabetes. A new large‐scale randomised trial, ADVANCE (Action in Diabetes and Vascular Disease), is also described.
Effect Of Vasodilatory β‐Adrenoceptor Blockers On Cardiovascular Haemodynamics In Anaesthetized Rats
Authors: Takahashi Hakuo , Masaki Hiroya , Komiyama Yutaka , Masuda Midori , Nishimura Masato 
Published: March 2003

SUMMARY1. The effect of vasodilatory β‐adrenoceptor blockers on regional blood flow in the major organs of anaesthetized rats was investigated using radioactive microspheres. The administration of propranolol and saline was used as a control.2. Intravenous injections of carvedilol (2 mg/rat), celiprolol (20 mg/rat) and bopindolol (1 mg/rat) equally decreased systemic blood pressure (SBP) by approximately 20 mmHg, whereas propranolol (1 mg/rat) decreased SBP only slightly but not significantly.3. Heart rate was significantly decreased by carvedilol, celiprolol, bopindolol and propranolol.4. Coronary blood flow was markedly increased by carvedilol, but not by the other three drugs.5. Cardiac output tended to decrease following the administration of all four drugs.6. Total peripheral vascular resistance was not significantly affected by carvedilol, celiprolol and bopindolol, but was markedly increased following propranolol.7. Renal blood flow was markedly increased by carvedilol.8. Blood flow in the brown fat was markedly increased by carvedilol and bopindolol, but not by celiprolol and propranolol.9. These findings indicate that the newer vasodilatory beta‐blockers, such as carvedilol and bopindolol, have a beneficial effect on the regional circulation in contrast with the classical beta‐blocker propranolol.10. The regional haemodynamic effects observed in the present study following intravenous injection of the beta‐blockers may help explain the clinical experience that vasodilatory beta‐blockers increase insulin sensitivity and decrease mortality in patients with congestive heart failure.