bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological Characterization Of Bradykinin B1 and B2 Receptors In IMR‐90 and INT‐407 Human Cell Lines Using A Microphysiometer
Authors: Bentley Kim R , Jarrott Bevyn 
Published: March 2003

SUMMARY1. In the present study, we used a microphysiometer to measure bradykinin‐induced acidification responses in IMR‐90, a human lung fibroblast cell line, and INT‐407, a human colonic epithelial cell line. Furthermore, we investigated the effect of 24 h exposure of transforming growth factor (TGF)‐α on the bradykinin response in INT‐407 cells.2. Bradykinin (0.1–100 nmol/L) was potent in producing acidification responses in IMR‐90 cells (pEC50 8.79±0.13; Hill slope 0.96±0.04) and INT‐407 cells (pEC50 8.90±0.04; Hill slope 1.00±0.07). These responses were competitively antagonized by the bradykinin B2 receptor antagonist icatibant in both IMR‐90 cells (apparent pKB = 8.54±0.15; Hill slope = 1.09±0.13 and 1.66±0.26 in the absence and presence of 10 nmol/L icatibant, respectively) and INT‐407 cells (pKB = 8.12±0.07 (3, 10 and 30 nmol/L icatibant); Hill slope = 1.06±0.04). However, the bradykinin B1 receptor antagonist des‐Arg9Leu8‐bradykinin (3 μmol/L) had no effect on the bradykinin responses.3. The non‐peptide bradykinin B2 receptor antagonist FR173657 selectively antagonized bradykinin‐induced acidification responses in INT‐407 cells in a competitive manner (pKB = 8.76±0.10; Hill slope = 0.92±0.05) at lower concentrations (1 and 3 nmol/L) but in an insurmountable manner at higher concentrations (10 nmol/L; Hill slope = 1.04±0.09). This compound, at concentrations of 10 and 100 nmol/L (Hill slope = 1.38±0.15), also proved to be an insurmountable antagonist in IMR‐90 cells.4. The bradykinin B1 receptor selective agonist Lys0des‐Arg10‐bradykinin (0.1 nmol/L to 0.1 μmol/L) failed to produce acidification responses in IMR‐90 cells, even after 24 h pre‐incubation with bacterial lipopolysaccharide (0.1 μg/mL).5. A 24 h pre‐incubation of INT‐407 cells with TGF‐α (1, 10 and 100 ng/mL) caused a significant concentration‐dependent decrease in maximal bradykinin response without affecting the pEC50.6. In addition to this study being the first to use a microphysiometer to characterize bradykinin B2 receptors in cultured IMR‐90 human lung fibroblast cells and INT‐407 human colonic epithelial cells, we also showed that pre‐incubation of INT‐407 cells with TGF‐α caused a significant decrease in maximal acidification response mediated by bradykinin B2 receptors.
Cyclo‐Oxygenase 2 Tissue Distribution And Developmental Pattern Of Expression In The Chicken
Authors: Mathonnet M , Lalloue F , Danty E , Comte I , Lièvre C Ayer‐Le 
Published: March 2003

SUMMARY1. Cyclo‐oxygenase 2 (COX‐2) is implicated in multiple physiopathological processes. We have studied its physiological expression during chicken embryogenesis.2. An original procedure was set to prepare a COX‐2 probe from red blood cells. In situ hybridization, reverse transcription–polymerase chain reaction and northern blots, were performed on chick embryos from embryonic day (E) 3 to postnatal day 15.3. In the mesonephros, the signal detected in mesonephric tubules presented a slow increase from E5 to E9, a plateau up to E12 and then a decrease, while the signal increased in the metanephros and then decreased after hatching. Transient expression of COX‐2 mRNA in endothelial cells of the infundibulum of the aorta was also detected between E12 and E17.4. This enzyme may have important roles in kidney morphogenesis during early embryonic stages and in tubular functions during development and in adult life. In the cardiovascular system, its vasodilatory effect could modulate the vasoconstrictor effect of the systolic pressure between E12 and E17 and contribute to a normal morphogenesis of the arterial tree and heart.
Role of endothelin‐1 receptors in healthy anaesthetized rabbits
Authors: Schmitz‐Spanke S , Schipke JD 
Published: March 2003

SUMMARY1. Many diseases are associated with elevated endothelin (ET)‐1 plasma concentrations. In order to understand the consequence of this elevation, in the present study the effects of exogenous ET‐1 on the entire organsim were investigated, in particular with respect to the role of ETA and ETB receptors in the cardiovascular system. In open‐chest rabbits, left ventricular (LV) pressure (LVPmax, LVPed), dP/dtmax and dP/dtmin were recorded in ejecting and isovolumically beating hearts to determine cardiac function. In addition, heart rate (HR), aortic pressure (AoP) and aortic flow (AoF) were measured. Total peripheral resistance (TPR) was calculated from mean AoP and AoF.2. In the first series of experiments (n = 11), ET‐1 (0.5 nmol/kg; bolus) produced a non‐significant reduction in HR. Systolic function, in terms of AoF, LVPmax and dP/dtmax, was improved; for example, LVPmax was increased significantly (69 ± 10 vs 106 ± 20 mmHg for control and ET‐1, respectively; P < 0.05). Similarly, early relaxation (dP/dtmin) was improved. In parallel, TPR rose significantly (0.25±0.07 vs 0.35±0.1 mmHg/min per mL for control and ET‐1, respectively; P < 0.05). Isovolumic measurements showed corresponding responses.3. In the second series of experiments (n = 7), animals were pretreated with an ETA receptor antagonist (330 nmol/min per kg FR 139317). After ETA receptor blockade, the administration of ET‐1 had no significant effect on cardiac function or vasomotion.4. In the third series of experiments (n = 6), animals were pretreated with an ETB receptor antagonist (10 nmol/min per kg BQ 788). In this series of experiments, the effects of ET‐1 on cardiac function and vasomotion were the same as in the first series of experiments, except for the effect on HR, which decreased by 35% after ET‐1.5. In our experimental model, exogenous ET‐1 exerted a clear‐cut positive inotropic effect, together with the anticipated peripheral vasoconstriction via ETA receptors.
Existence Of α1A‐ and α1B‐Adrenoceptor Subtypes In Canine Mandibular Alveolar Arteries
Authors: Taguchi Yuichi , Yang Xiao‐Ping , Chiba Shigetoshi 
Published: March 2003

SUMMARY1. The present study attempted to pharmacologically characterize the α‐adrenoceptor subtypes mediating vasoconstriction in canine isolated and perfused mandibular alveolar artery (MAA).2. Noradrenaline (NA) and phenylephrine (PE) induced a strong vasoconstriction in a dose‐dependent manner. The PE‐induced vascular constriction was significantly inhibited by treatment with prazosin. Xylazine evoked a moderate vascular constriction and the xylazine‐induced response was suppressed by rauwolscine. The NA‐induced response was partially inhibited by rauwolscine and the remaining response to NA was abolished by subsequent administration of prazosin.3. Treatment of MAA with WB4101 produced a dose‐ dependent inhibition of NA‐induced vasoconstriction. Pretreatment of tissues with 10 μmol/L chloroethylclonidine produced a slight and statistically significant inhibition of NA‐induced responses. BMY 7378, a selective α1D‐adrenoceptor antagonist, failed to significantly affect vasoconstrictor responses to NA.4. The present results suggests that: (i) both α1‐ and α2‐adrenoceptors are involved in vasoconstrictor responses in the canine MAA; and (ii) the α1‐adrenoceptors involved in the vasoconstrictor responses in the MAA are characterized as mainly of the α1A‐ and partially of the α1B‐adrenoceptor subtype.
Effects Of Optic Tract Stimulation On Baroreflex Vagal Bradycardia In Rats
Authors: Cheng Zhi Bin , Kobayashi Masayoshi , Nosaka Shoichiro 
Published: March 2003

SUMMARY1. Arterial baroreflexes are suppressed in stressful conditions. Intense visual stimuli can cause a threatening sensation and produce defensive reactions.2. The present study was designed to determine whether and how electrical stimulation of the optic tract (OT) affects arterial baroreflexes, especially the heart rate component, baroreflex vagal bradycardia (BVB), in rats. In chloralose– urethane anaesthetized, β‐adrenoceptor‐blocked rats, BVB was evoked by electrical stimulation of the aortic depressor nerve.3. Electrical stimulation of the OT was found to not only increase blood pressure and heart rate, but also to inhibit BVB. To determine whether these responses were mediated by the lateral genticulate body and/or the superior colliculus, which are major target sites to which the OT projects, each was activated with electrical and chemical stimulation.4. The lateral genticulate body did not respond to either electrical or chemical stimulation, whereas the superior colliculus increased blood pressure and heart rate while suppressing BVB following electrical stimulation. Essentially similar responses were observed following microinjection of the GABA antagonist bicuculline methiodide.5. Optic tract‐induced inhibition of BVB was abolished by bilateral destruction of the superior colliculus. Furthermore, this inhibition was also largely attenuated by destruction of the midbrain periaqueductal grey (PAG).6. In conclusion, electrical stimulation of the OT increases blood pressure, heart rate and inhibits BVB. These responses are not mediated by the lateral genticulate body but are mediated by the superior colliculus. The PAG may participate in the subsequent mediation of the responses to electrical stimulation of the OT and the OT‐induced inhibition of BVB may contribute to expression of a light‐induced defence reaction.
The Many Essential Interfaces Of Clinical Pharmacology
Authors: Shenfield Gillian M 
Published: March 2003

SUMMARY1. Clinical pharmacology requires numerous skills and most activities involve interactions with other specialities, both clinical and experimental.2. A range of experts has had a major influence on the nature and design of my research, which is illustrated by the evolution of my knowledge of adverse drug reactions and how to prevent them.3. Clinical pharmacologists are uniquely placed to coordinate programmes to achieve quality use of medicines. but we will only achieve our aims if multiple interactions with other experts are encouraged and developed.
Fetal Growth And Programming Of The Hypothalamic–Pituitary–Adrenal Axis
Authors: Phillips David Iw 
Published: March 2003

SUMMARY1. Epidemiological studies have shown that small size at birth is associated with an increased risk of coronary heart disease and its risk factors, including hypertension and type 2 diabetes.2. It is suggested that these observed links between low birthweight with disease result from an imbalance between fetal nutrient demand and supply. This imbalance results in metabolic and endocrine adaptations that benefit the fetus in the short term by reducing fetal growth and increasing fuel availability but, in the longer term, are maladaptive, leading to an increased risk of coronary heart disease.3. Experimental data in animals and recent human observations have suggested that an alteration in the set point of the hypothalamic–pituitary–adrenal axis is an important long‐term change that occurs in association with reduced fetal growth.4. These data raise the possibility that the nature and amplitude of the stress response may be determined by intra‐uterine factors.
Is Prenatal Glucocorticoid Administration Another Origin Of Adult Disease?
Authors: Newnham John P 
Published: March 2003

SUMMARY1. The intra‐uterine environment is now believed to play a major role in the origin of many adult diseases. Illnesses in which there is significant ‘programming’ before the time of birth include hypertension, diabetes, coronary heart disease and stroke. Acting on a genetic predisposition, intra‐uterine triggers appear to programme the individual’s metabolism and endocrine milieu and, after birth, these risk factors are then either amplified or minimized by environmental influences. The triggers operative during fetal life that have been studied most extensively are undernutrition and glucocorticoid exposure.2. Over the past decade, a series of studies in sheep have focused on the perinatal and life‐long consequences of glucocorticoid exposure in mid‐ to late‐pregnancy. These studies in the sheep model have shown that maternal injections with glucocorticoids, in a manner similar to clinical treatment for women at risk of preterm birth, enhance fetal lung maturation, but were also associated with developmental and other functional alterations that are of concern. With weekly doses to the mother, there is restricted fetal growth, delayed myelination of the central nervous system, altered blood pressure soon after birth and increased insulin response to glucose challenge in early adulthood. If the glucocorticoids are given to the fetus by ultrasound‐guided intramuscular injection, rather than to the mother, the effects on lung maturation are similar, but growth is spared and blood pressure after birth is unaltered. Increased insulin response to glucose challenge occurs in early adulthood with glucocorticoid by either route and is independent of growth restriction.3. The findings in experimental animals are supported by studies of children in the Western Australian Preterm Infant Follow‐up Study. Multivariate analyses have shown that increasing the number of glucocorticoid exposures, for the purpose of enhancing lung maturation prior to preterm birth, is associated with reduced birthweight and behavioural disorders at 3 years of age.4. The results of these animal and clinical studies provide further support for a role of prenatal glucocorticoid exposure in triggering predisposition to adult disease. Further exploration of these models is expected to uncover the mechanisms and lead to effective strategies that may underpin clinical interventions.
Possible Involvement Of P‐Glycoprotein In The Biliary Excretion Of Grepafloxacin
Authors: Zhao Ying Lan , Cai Shao Hui , Wang Li , Kitaichi Kiyoyuki , Tatsumi Yasuaki , Nadai Masayuki , Yoshizumi Hideo , Takagi Kenji , Takagi Kenzo , Hasegawa Takaaki 
Published: March 2003

SUMMARY1. In the present study, we have examined the effects of the quinolones norfloxacin (NFLX), enoxacin (ENX), ofloxacin (OFLX), tosufloxacin (TFLX), lomefloxacin (LFLX), sparfloxacin (SPFX) and grepafloxacin (GPFX) on the efflux of doxorubicin from mouse leukaemia P388/ADR cells expressing P‐glycoprotein. The relationship between their partition coefficients (hydrophobicity) and effluxing potencies was also elucidated.2. Both TFLX and SPFX strongly increased the intracellular accumulation of doxorubicin (5 μmol/L) in P388/ADR cells, but had no effect on P388/S cells not expressing P‐glycoprotein. The rank of order of the potency of the quinolones (TFLX > SPFX > GPFX > NFLX) was not related directly to their hydrophobicity. These results suggest that some quinolones can reverse anticancer drug resistance.3. Because GPFX is more highly excreted into the bile than other known quinolones, the effects of doxorubicin (10 mg/kg) or the well‐known inhibitors of P‐glycoprotein, namely cyclosporine A (10 mg/kg) and erythromycin (100 mg/kg), on the biliary excretion of GPFX at steady state was studied in rats.4. Doxorubicin, cyclosporine A and erythromycin significantly decreased the biliary clearance of GPFX. Cyclosporine A and erythromycin had a much stronger inhibitory effect on the biliary excretion of GPFX than doxorubicin. These results suggest the possibility that GPFX is, at least in part, excreted into the bile by a P‐glycoprotein‐mediated transport mechanism.
Dendroaspis Natriuretic Peptide Administered Intracerebroventricularly Increases Renal Water Excretion
Authors: Lee JongUn , Kim Soo Wan 
Published: March 2003

SUMMARY1. The effects of intracerebroventricular (i.c.v.) infusion of Dendroaspis natriuretic peptide (DNP) on renal function were examined in anaesthetized rats. The results were compared with those obtained following intravenous (i.v.) infusion of the same dose of DNP.2. Urine volume was increased four‐ to six‐fold over basal values by i.c.v. infusion of DNP (6 pmol/min). Urine osmolality was decreased, whereas sodium excretion was not significantly altered. Intravenous infusion of the same dose of DNP had little effect on urinary water excretion. Neither arterial pressure nor heart rate was changed significantly by either i.v. or i.c.v. infusion of DNP. Glomerular filtration rate, measured by creatinine clearance, remained unaltered.3. The diuretic response to i.c.v. DNP was markedly attenuated in rats that were deprived of their water supply for 3 days before the experiment.4. These results suggest that DNP can act within the central nervous system to increase renal water excretion.
Sympathoinhibitory Action Of Nociceptin In The Rat Spinal Cord
Authors: Brailoiu GC , Lai CC , Chen CT , Hwang LL , LIN HH , Dun NJ 
Published: March 2003

SUMMARY1. Whole‐cell patch recordings were made from antidromically identified sympathetic preganglionic neurons (SPN) of immature rat spinal cord slices. Bath application of nociceptin (0.1–1 μmol/L) suppressed excitatory postsynaptic potentials (EPSP) and hyperpolarized a population of SPN; these effects were naloxone (1 μmol/L) insensitive.2. Nociceptin suppressed the amplitude of EPSP without causing a concomitant change in glutamate‐induced depolarizations, suggesting a presynaptic inhibitory action.3. Analysis of current–voltage relationships showed that nociceptin hyperpolarized SPN by increasing an inwardly rectifying K+ current.4. Intrathecal injection of nociceptin (3, 10 and 30 nmol) to urethane‐anaesthetized rats dose‐dependently reduced the mean arterial pressure and heart rate; these effects were not prevented by prior intravenous injection of naloxone (1 mg/kg).5. Results from our in vitro and in vivo experiments suggest that nociceptin suppresses spinal sympathetic outflow either by attenuating excitatory synaptic responses or hyperpolarizing SPN.
Neutrophil Migration During Liver Cirrhosis In Rabbits
Authors: Penteado FC , Ferreira HHA , Calafatti SC , Bernascconi G , Piovesana H , Pedrazzoli J 
Published: March 2003

SUMMARY1. The aim of the present study was to investigate neutrophil chemotaxis during the induction of liver cirrhosis in rabbits.2. Liver cirrhosis was induced in male New Zealand white rabbits. The study consisted of three experimental groups: (i) group A (n = 16) served as the control and
received only normal chow and all rabbits in this group were killed at 16 weeks;
(ii) group B rabbits (n = 8) were killed immediately after the chemotaxis
assay, which was performed 24 h after CCl4 administration, at weeks 2,
4, 6 and 8; and (iii) in group C rabbits (n = 19), the chemotaxis assay was
performed every second week on the day before CCl4 administration for 16 weeks and all animals in this group were killed at 16 weeks.3. Four of six rabbits in group B had liver cirrhosis at week 8. In group C, liver cirrhosis occurred in seven of eight animals. All rabbits with liver cirrhosis had an inflammatory infiltrate of neutrophils. In group B, there was a significant increase in polymorphonuclear cells and neutrophil chemotaxis and a significant reduction in mononuclear leucocytes at week 8. The rabbits in group C showed a significant increase in total leucocyte and polymorphonuclear numbers at week 10. A significant increase in neutrophil chemotaxis was also observed from week 2 through to week 6.4. The presence of neutrophils in the liver of all rabbits with cirrhosis, associated with an increase in polymorphonuclear cell chemotaxis during this process, supports the view that this cell type has an important role in the development of toxic liver damage.
Oxidative Stress And Potassium Channel Function
Authors: Liu Yanping , Gutterman David D 
Published: March 2003

SUMMARY1. Modulation of K+ channel activities by cellular oxidative stress has emerged as a significant determinant of vasomotor function in multiple disease states.2. Evidence from in vitro and in vivo studies suggest that superoxide
(O2–) and hydrogen peroxide (H2O2)
enhance BKCa channel activity in rat and cat cerebral arterioles; however,
activity is decreased by peroxynitrite (ONOO–) in rat cerebral
arteries. The mechanisms of changes in BKCa channel properties are not fully understood and may involve oxidation of cysteine residues that are located in the cell membranes.3. Studies further suggest that O2– increases KATP
channel activity in guinea‐pig cardiac myocytes, but decreases opening in cerebral
vasculature. Both H2O2 and ONOO– enhance
KATP channel activity in the myocardium and in coronary, renal, mesenteric
and cerebral vascular beds. Alteration of KATP channels by free radicals may be due to oxidation of SH groups or changes in the cytosolic concentration of ATP.4. It does appear that O2– produced by either reaction
of xanthine and xanthine oxidase or elevated levels of glucose reduces Kv channel activity and the impairments can be partially restored by free radical scavengers, superoxide dismutase and catalase.5. Thus, redox modulation of potassium channel activity is an important mechanism regulating cell vascular smooth muscle membrane potential.
Cellular Coupling And Conducted Vasomotor Responses
Authors: Neild TO , Crane GJ 
Published: March 2003

SUMMARY1. The present brief review examines the concept of spreading vasodilator responses in arteriolar trees, its physiological relevance and possible mechanisms.2. The most likely mechanisms involve spread of hyperpolarization through tissues in the vessel wall, made possible by electrical coupling between the cells. It is generally agreed that there is coupling between cells within the muscle and endothelial layers, but coupling between the two layers is not always present.3. The passive electrical properties of arterioles can be modelled, using different techniques depending on the complexity of branching of the arteriolar tree. Comparison of experimental results with the model indicates that hyperpolarization can spread further than expected from passive properties alone, implying that spreading vasodilatation may be an active process.