bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact Of Physical And Physiological Factors On Arterial Function
Authors: McGrath BP , Liang Y‐L , Kotsopoulos D , Cameron JD 
Published: March 2003

SUMMARY1. Arterial function measurements are increasingly used as surrogate markers of cardiovascular disease and it is important to define which non‐pathological factors may influence these measurements.2. The present study examined the influence of gender, height, body mass index (BMI), waist : hip ratio, heart rate and arterial pressure on pulse wave velocity (PWV), systemic arterial compliance (SAC) and central pressure augmentation index (AI) in 285 normal subjects, 98 males and 187 females, aged 50–82 years.3. There were significant gender differences in PWV (higher in men), SAC (higher in men) and central pressure AI (lower in men).4. Both SAC and AI were correlated with height in men and women and height largely accounted for gender differences.5. Systemic arterial compliance was positively, whereas AI was negatively, correlated with BMI.6. Both PWV and AI were significantly correlated with heart rate and central pulse pressure.7. These findings may have implications for cardiovascular disorders. Reduced central arterial compliance and increased central pressure augmentation are potential mediators for the increased cardiovascular risk of short stature. A slow heart rate may contribute to increased central arterial pressure with potentially adverse consequences in older subjects.
Acute Effects Of L‐ And T‐Type Calcium Channel Antagonists On Cardiovascular Reflexes In Conscious Rabbits
Authors: Devlin Mark G , Angus James A , Wilson Kathryn M , Wright Christine E 
Published: March 2003

SUMMARY1. The effects of the relatively selective T‐type voltage‐ operated calcium channel (VOCC) antagonist mibefradil were compared with verapamil, an L‐type VOCC antagonist, on a range of autonomic reflexes in conscious rabbits.2. Mean arterial pressure (MAP), heart rate (HR), the baroreceptor–HR reflex, postural adaptation reflex (90°head‐up tilt), Bezold–Jarisch‐like reflex and the vasoconstrictor component of the nasopharyngeal reflex were assessed before and during i.v. infusion of vehicle (saline), mibefradil or verapamil. Doses of mibefradil that gave low (M1; 0.45±0.02μg/mL) and high (M2; 0.93±0.05μg/mL) plasma concentrations, or verapamil (0.059±0.004μg/mL;n= 6 each) were chosen to mimic clinically observed therapeutic levels.3. At steady state infusion over 30–90 min, MAP was significantly lower in M2 (– 7 mmHg) and verapamil (– 6 mmHg) treatments, but only verapamil caused a significant tachycardia (+ 31 b.p.m.) compared with vehicle. Mibefradil (M2) and verapamil decreased the HR range of the baroreflex by 27 and 29%, respectively, but neither treatment affected the vagal or sympathetic constrictor components of the Bezold–Jarisch‐like and nasopharyngeal reflexes, respectively.4. In response to 90°tilt, vehicle‐ and verapamil‐treated rabbits responded with small rises in MAP of 4±2 and 8±2 mmHg, respectively, 5 s into the upright posture, while M1 and M2 caused falls in MAP of 6±4 and 9±3 mmHg, respectively, at 5 s.5. Thus, both L‐ and T‐type VOCC antagonists, at plasma concentrations in the clinical range, lowered MAP in the conscious rabbit, but only mibefradil caused postural hypotension. We conclude that T‐type VOCC may play an important role in the venoconstrictor reflex in response to tilt in the rabbit.
Inhibition Of Proliferation And Signalling Mechanisms In Human Lymphocytes By Fluvastatin
Authors: Hillyard Dianne Z , Cameron Angus JM , McIntyre Alan H , Hadden Mark H , Marshall Hilary E , Johnston Nicola , Jardine Alan G 
Published: March 2003

SUMMARY1. Inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase (statins) reduce serum cholesterol and have proven benefits in the treatment of cardiovascular disease. However, recent work suggests that statins may exert immunosuppressive effects in isolated lymphocytes and in solid organ transplant recipients. Fluvastatin does not interfere with the metabolism of commonly used immunosuppressive agents and, therefore, may have benefits in transplant recipients.2. The aim of the present study was to investigate the potential immunomodulatory effects of fluvastatinin vitroin human lymphocytes and the underlying effects on signal transduction.3. In vitro, fluvastatin (10μmol/L) caused a time‐dependent inhibition of T cell proliferation in response to cross‐linking of CD3.4. Thymidine incorporation was reduced by 22, 81 and 92% at days 1, 3 and 5, respectively.5. Mevalonate (1μmol/L) treatment for 4 or 24 h significantly reduced the inhibitory effects of fluvastatin; the reversal was abrogated by simultaneous exposure to mevalonate and a farnesyl transferase inhibitor.6. At a subcellular level, fluvastatin treatment was associated with reduced functional activity of Ras‐dependent extracellular signal‐regulated kinase pathways and of Rho‐dependent p38 activation.7. These data suggest that the potential immunosuppressive actions of statins involve inhibition of subcellular pathways dependent on isoprenylation of signal peptides, including Ras, Rho and related G‐proteins.
Effects of indomethacin on responses of regional kidney perfusion to vasoactive agents in rabbits
Authors: Oliver Jeremy J , Rajapakse Niwanthi W , Evans Roger G 
Published: March 2003

Summary1. To determine whether differential release of products of arachidonic acid metabolism, via the cyclo‐oxygenase pathway, underlies the diversity of responses of regional kidney perfusion to vasoactive agents, we tested the effects of intravenous indomethacin on responses to renal arterial bolus doses of vasoactive agents in pentobarbitone‐anaesthetized rabbits.2. Total renal blood flow (RBF) and regional kidney perfusion were determined by transit time ultrasound flowmetry and laser‐Doppler flowmetry, respectively.3. Responses of regional kidney blood flow to vasoactive agents were diverse: noradrenaline reduced cortical but not medullary perfusion, [Phe2,Ile3,Orn8]‐vasopressin reduced medullary perfusion more than cortical perfusion, endothelin‐1 and angiotensin II increased medullary perfusion in the face of reduced cortical perfusion, while acetylcholine, bradykinin and the nitric oxide donor methylamine hexamethylene methylamine (MAHMA) NONOate all increased both cortical and medullary perfusion.4. Indomethacin administration was followed by reductions in total RBF (17 ± 6%), cortical perfusion (13 ± 5%) and medullary perfusion (40 ± 8%). Angiotensin II‐ and endothelin‐1‐induced increases in medullary perfusion were abolished by indomethacin, but indomethacin had no significant effects on responses of regional kidney perfusion to acetylcholine, bradykinin, MAHMA NONOate, noradrenaline and [Phe2,Ile3,Orn8]‐vasopressin.5. Our results suggest that vasodilator cyclo‐oxygenase products contribute to the maintenance of resting renal vascular tone, particularly in vascular elements controlling medullary perfusion. Cyclo‐oxygenase products also appear to mediate endothelin‐1‐ and angiotensin II‐induced increases in medullary perfusion. However, regionally specific engagement of cyclo‐oxygenase‐dependent arachidonic acid metabolism does not appear to contribute to the differential effects of noradrenaline and [Phe2,Ile3,Orn8]‐vasopressin on cortical and medullary perfusion.
Neural control of the renal vasculature in angiotensin II‐induced hypertension
Authors: Ramchandra Rohit , Barrett Carolyn J , Guild Sarah‐Jane , Malpas Simon C 
Published: March 2003

Summary1. Chronic administration of angiotensin (Ang) II causes an increase in blood pressure via a multitude of actions, including direct vasoconstriction, hypertrophy and increased sympathetic nerve activity. In the present study, we assessed whether the hypertension resulting from chronic AngII alters the ability of the renal vasculature to respond to sympathetic activity.2. Angiotensin II was administered for 7 weeks via an osmotic minipump at a dose of 50 ng/kg per min, i.v., to a group of six rabbits. Blood pressure, measured at 0, 1, 2 and 6 weeks after insertion of the pump, increased from 76 ± 2 to 104 ± 6 mmHg at the end of 6 weeks, without any significant change in heart rate. The blood pressure in the control group remained constant at 76 ± 2 mmHg.3. After 7 weeks, rabbits were anaesthetized and the renal nerves were stimulated at 0.5, 1, 1.5, 2, 3, 5 or 8 Hz for 3 min at their supramaximal voltage (5.5 ± 1.0 V in the normotensive group and 6.5 ± 1.5 V in the hypertensive group) while the renal blood flow (RBF) response was recorded. Under anaesthesia, there was no difference in mean arterial pressure between the normotensive and hypertensive animals (77 ± 2 and 80 ± 7 mmHg, respectively). The resting RBF under these conditions was not significantly different in the hypertensive group (30 ± 4 vs 26 ± 5 mL/min in the normotensive vs hypertensive group, respectively).4. Stimulation at increasing frequencies was associated with increasing reductions in RBF (e.g. 36 ± 8% at 2 Hz in normotensive rabbits and 48 ± 7% at 2 Hz in hypertensive rabbits). However, there were no significant differences between RBF responses in normotensive and hypertensive rabbits.5. We conclude that hypertension associated with chronic AngII administration does not alter the response in RBF to electrical stimulation of the nerves.
Propofol differently alters vascular reactivity in normotensive and hypertensive rats
Authors: Samain Emmanuel , Clichet Adeline , Bouillier Hélène , Chamiot‐Clerc Philippe , Safar Michel , Marty Jean , Renaud Jean‐François 
Published: March 2003

Summary1. The effect of propofol on arterial tone in hypertension is poorly understood. We examined the effect of increasing concentrations of propofol (5.6 × 10−8 to 2.8 × 10−3 mol/L) on isometric tension developed by noradrenaline (10−7 mol/L)‐contracted aortic rings from 12‐week‐old Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).2. In both WKY rats and SHR, propofol induced a dose‐dependent inhibition of contraction induced by noradrenaline, but the amplitude of relaxation was larger in the SHR than in WKY rats.3. The effects of propofol was endothelium independent in WKY rats, whereas in SHR relaxation induced by propofol was greater in endothelium‐intact than in endothelium‐denuded rings.4. In conclusion, we found significant differences in the effect of propofol in hypertensive rats, which may be related to differences in structural and functional properties of the arterial wall observed in hypertension.
Effect of oestrone on membrane fluidity of erythrocytes is mediated by a nitric oxide‐dependent pathway: An electron paramagnetic resonance study
Authors: Tsuda Kazushi , Kinoshita‐Shimamoto Yukiko , Kimura Keizo , Nishio Ichiro 
Published: March 2003

Summary1. It has been recognized that hormone replacement therapy (HRT) may have a beneficial effect on protection against cardiovascular diseases. Oestrone is the major component of conjugated equiline oestrogens, which are commonly used in HRT. The present study was performed in order to investigate the effects of oestrone on the membrane fluidity of erythrocytes by means of an electron paramagnetic resonance (EPR) and spin‐labelling method.2. In an in vitro study, oestrone significantly decreased the order parameter (S) for 5‐nitroxide stearate (5‐NS) and the peak height ratio (ho/h‐1) for 16‐nitroxide stearate (16‐NS) obtained from EPR spectra of erythrocyte membranes. This finding indicated that oestrone may increase the membrane fluidity and improve the membrane microviscosity of erythrocytes.3. The effect of oestrone was significantly potentiated by the nitric oxide (NO) donor s‐nitroso‐N‐acetylpenicillamine and the cGMP analogue 8‐bromo‐cGMP.4. In contrast, the change in membrane fluidity induced by oestrone was antagonized by the NO synthase inhibitors NG‐nitro‐l‐arginine methyl ester and asymmetric dimethyl‐l‐arginine.5. The results of the present study show that oestrone significantly increases membrane fluidity and improves the rigidity of cell membranes, which is partially mediated by a NO‐ and cGMP‐dependent pathway. Furthermore, the data may be consistent with the hypothesis that oestrone could have a beneficial effect on the rheological behaviour of erythrocytes and have a crucial role in the regulation of the microcirculation.
Effects of vascular endothelial growth factor (VEGF)A and VEGFB gene transfer on vascular reserve in a conscious rabbit hindlimb ischaemia model
Authors: Wright Christine E 
Published: March 2003

Summary1. As a result of the ageing population, there are increasing numbers of patients with severe peripheral vascular occlusive disease associated with intermittent claudication (pain on walking) and decreased exercise tolerance. There is a great clinical need for pharmacological treatments that may stimulate collateral blood vessel growth, increase vascularity and improve skeletal muscle function.2. Therapeutic angiogenesis using growth factors such as vascular endothelial growth factor (VEGF) has been used to improve collateral artery development in myocardial or skeletal muscle ischaemia. The broad aims of the work briefly summarized here were to compare the effects of VEGFA165 and VEGFB167 (500 µg, i.m., gene transfer) on calf blood pressure ratio and reactive hyperaemia in a chronic rabbit preparation with unilateral limb ischaemia.3. Unilateral femoral artery ligation caused an immediate deficit (compared with the contralateral limb) of 72% in calf systolic blood pressure. There were improvements 14 days after ligation with VEGFA and VEGFB treatments compared with the vehicle control plasmid treatment, but a deficit remained of some 32%.4. Reactive hyperaemic responses were significantly attenuated 7 days after ligation in the vehicle and VEGFA treatment groups. On day 14, this loss of vascular reserve was restored in the VEGFA group, but remained in the vehicle group (−30%). In VEGFB‐treated animals, there was no deficit in reserve 7–14 days post‐ligation.5. In conclusion, there is considerable value in the serial measurements of calf blood pressure ratio and reactive hyperaemia in the rabbit unilateral hindlimb ischaemia model. Gene transfer of either VEGFA or VEGFB allowed significant improvements in these indices compared with vehicle but, at 14 days post‐ligation, large deficits still remained. Studies extending this experimental period are in progress.
Effects of polarizing solution on glucose uptake of rat oxygenated or hypoxic ventricular myocytes
Authors: Carbó Roxana , Nava Pilar , Guarner Verónica 
Published: March 2003

Summary1. Although adult cardiac metabolism depends on fatty acids rather than on carbohydrates, hypoxic hearts consume glucose and infusion with a glucose–insulin–potassium solution (GIK) helps in the recovery of the pressure register, the heart rate and electrocardiogram of rat hypoxic whole hearts.2. Rat myocytes obtained by enzymatic disaggregation captured significant amounts of glucose in Tyrode's solution (9.8 ± 2.05% during oxygenation and 16.26 ± 2.76% during hypoxia) after 60 min incubation. Cells incubated with GIK showed a significantly increased glucose uptake (to 30.04 ± 1.99% during oxygenation and to 37.06 ± 1.97% during hypoxia).3. Glucose was the component of the Tyrode's solution that most enhanced its own entry, increasing glucose entry to 45.42 ± 2.64% with oxygen and 41.42 ± 2.69% under hypoxia.4. Antibodies against glucose transporters 1 and 4 (GLUT‐1 and ‐4, respectively) decreased glucose transport during GIK treatment under hypoxia.5. We conclude that GIK has beneficial effects mediated by GLUT‐1 and ‐4 during hypoxia, inducing recovery of the damaged tissue.
Restoration of osmotically inhibited twitch force in rat cardiac trabeculae: Role of Na+–H+ exchange
Authors: Cropper JRD , Erac I , Loiselle DS 
Published: March 2003

Summary1. When rat cardiac muscle is subjected to an increase of osmolality, its peak twitch force is immediately inhibited. Subsequently, over a period of several minutes, twitch force undergoes restoration, the extent of which is determined by the osmolality. The aim of the present study was to determine the factors that contribute to this restorative phenomenon.2. Trabeculae were isolated from the right ventricles of rat hearts and mounted in an organ bath at 37°C. The osmolality of the bathing solution was increased by 100 mOsmol (to 400 mOsmol) by the addition of various proportions of NaCl and sucrose while recording twitch force production. The role of Na+–H+ exchange in restoring twitch force was examined by use of the specific inhibitor cariporide (HOE 642). The role of Na+–Ca2+ exchange was examined by reducing [Ca2+]o (from 2 mmol/L to 0.5 mmol/L) or by substituting LiCl for NaCl.3. Cariporide (25 µmol/L) completely abolished twitch force restoration, thereby implicating a central role for the Na+–H+ exchanger. At constant [Na+]o, the extent of restoration was [Ca2+]o dependent, suggesting an independent contribution by the Na+–Ca2+ exchanger. This suggestion was supported by the finding that Li+, which substitutes for Na+ on the Na+–H+ exchanger, but not on the Na+–Ca2+ exchanger, also reduced the extent of restoration of hyperosmotically inhibited twitch force.4. We conclude that the immediate inhibition of peak twitch force of rat cardiac muscle by hyperosmotic solutions reflects, in part, elevation of [H+]i, subsequent to reduction of cell volume. Hyperosmotic activation of Na+–H+ exchange then progressively relieves the inhibitory effect of protons on force development. The accompanying increase in [Na+]i in turn enhances Ca2+ influx on the Na+–Ca2+ exchanger, with the result that twitch force undergoes further restoration.
Inhibition of nuclear translocation of transcription factor nuclear factor‐κB induces FAS‐ as well as tumour necrosis factor‐α‐mediated apoptosis through downregulation of a conserved family of inhibitor of apoptosis 1
Authors: Imanishi Toshio , Hano Takuzo , Takarada Shigeho , Nishio Ichiro 
Published: March 2003

Summary1. In the present study, we examined whether the nuclear transcription factor (NF)‐κB activity plays a role in the determination of sensitivity to tumour necrosis factor (TNF)‐α or agonistic Fas antibody (Ab) in human vascular smooth muscle cells (hVSMC).2. To inhibit agonist‐induced NF‐κB activation in hVSMC, a cell‐permeable peptide (SN50), which carried the nuclear localization sequence of the NF‐κB p50 subunit, was used. Nuclear factor‐κB activity was examined by both immunoblot analysis of nuclear extracts and by ELISA. The hVSMC were treated with TNF‐α or agonistic Fas Ab (CH11) and then apoptosis was determined by cell death ELISA for DNA fragmentation. To investigate the mechanisms for protection against apoptosis in hVSMC, we analysed the expression of a conserved family of inhibitor of apoptosis 1 (c‐IAP1) protein using immunoblot analysis.3. Although both CH11 and TNF‐α alone failed to induce hVSMC death in the presence of SN50, they markedly increased the apoptotic hVSMC estimated by cell death ELISA. In addition, these effects could be blocked with the pan‐caspase inhibitor z‐VAD.fmk. Western blotting analysis indicated that TNF‐α alone increased c‐IAP1 protein levels, whereas CH11 alone had no effect. Inhibition of NF‐κB activation by SN50 suppressed c‐IAP1 protein expression and enhanced apoptosis induced by either TNF‐α or CH11.4. These findings suggest that c‐IAP1 is an important intracellular modulator of Fas as well as TNF‐α death signalling pathways in hVSMC. The expression of c‐IAP1 is regulated by a NF‐κB‐mediated phenomenon.
Validation of a portable indirect calorimeter (Metavine®) for measuring energy expenditure in an elderly population
Authors: Kato Masahiko , Tajika Masahiro , Miwa Yoshiyuki , Moriwaki Hisataka 
Published: March 2003

Summary1. The aim of the present study was to evaluate the usefulness and reliability of a portable indirect calorimeter (Metavine; Vine, Tokyo, Japan).2. We measured energy expenditure (EE) of elderly people (n = 191) at nursing homes using both Metavine and an authorized indirect calorimeter (Deltatrac Metabolic Monitor; Datex, Helsinki, Finland) and compared them.3. Energy expenditure measured by Metavine® significantly correlated with EE measured by the Deltatrac Metabolic Monitor (P < 0.001).4. In particular, Metavine gave almost same results as the Deltatrac Metabolic Monitor, showing an excellent reliability, within the range of EE from 800 to 1500 kcal/day. However EE measured by Metavine below 800 kcal/day or above 1500 kcal/day required correction to agree with EE as measured by the Deltatrac Metabolic Monitor.5. In conclusion, Metavine is a useful portable calorimeter for measuring EE in elderly people when used with sufficient recognition of its characteristics of data acquisition.
Studies on fertilization in the teleost IV. Effects of aphidicolin and camptothecin on chromosome formation in fertilized medaka eggs
Authors: Iwamatsu Takashi , Shibata Yasushi , Hara Osamu , Yamashita Masakane , Ikegami Susumu 
Published: March 2003

To clarify the mechanisms of fish fertilization, the effects of inhibitors of DNA polymerase‐α and DNA topoisomerases on nuclear behavior before and after fertilization were examined in eggs of the medaka, Oryzias latipes. Eggs underwent the fertilization process from sperm penetration to karyogamy of pronuclei, even when inseminated and incubated in the continuous presence of aphidicolin (DNA polymerase α inhibitor), camptothecin (DNA topoisomerase I inhibitor), etoposide, or β‐lapachone (DNA topoisomerase II inhibitor). However, continuous treatment with aphidicolin or camptothecin during fertilization inhibited the formation of sister chromosomes that were normally separated into blastomeres at the time of the subsequent cleavage. Sister chromosome formation appeared concomitantly with an increase in histone H1 kinase activity at the end of DNA synthesis, 30 min post insemination. However, non‐activated eggs that were inseminated in saline containing anesthetic MS222 and aphidicolin had high levels of histone H1 kinase and MAP kinase activities, and transformation of the penetrated sperm nucleus to metaphase chromosomes occurred even in the presence of aphidicolin or camptothecin. The male chromosomes were normally separated into two anaphase chromosome masses upon egg activation. These results suggest that DNA polymerase α or DNA topoisomerase I, but not DNA topoisomerase II, may be required for the process by which the mitotic interphase nucleus transforms to separable metaphase chromosomes while the activity of MAP kinase is low, unlike the situation in meiotic division, during which MAP kinase activity is high and DNA replication is not required.