bluuebunny/crossref_metadata_2025_split huggingface dataset:
LACK OF SYMPATHETIC AUGMENTATION IN RESPONSE TO INTRAVENOUS LOAD OF GLUCOSE IN RABBITS
Authors: Takishita Shuichi , Takata Yutaka , Abe Isao , Tomita Yuji , Kawazoe Nobuyuki , Fujishima Masatoshi , Fukiyama Koshiro 
Published: June 2007

SUMMARY1. We investigated a link between sympathetic nervous function and carbohydrate metabolism by measuring renal sympathetic nerve activity in response to intravenous load of glucose in α‐chloralose‐urethane anaesthetized rabbits.2. Intravenous infusion of a 25% glucose solution (0.5 g/kg) over 3 min caused a transient increase in arterial blood pressure and a decrease in renal sympathetic nerve activity. Thereafter, these parameters were restored and remained around preload levels while plasma glucose and insulin concentrations were still elevated.3. Equimolar mannitol solution produced similar patterns of change in blood pressure and nerve activity without an elevation of plasma glucose and insulin levels.4. The transient changes in blood pressure and renal nerve activity could be attributed to acute hypervolaemia indicated by similar changes in plasma osmolality and haematocrits in the two groups of treatment.5. The present study did not support a close relationship between carbohydrate metabolism and the sympathetic nervous system regulating cardiovascular function.
DIFFERENTIAL EFFECTS ON ACTION POTENTIAL DURATION OF CLASS IA, B AND C ANTIARRHYTHMIC DRUGS: MODULATION BY STIMULATION RATE AND EXTRACELLULAR K+ CONCENTRATION
Authors: Campbell Terence J. , Wyse Kenneth R. , Pallandi Regan 
Published: June 2007

SUMMARY1. Standard microelectrode techniques were used to study the effects on the action potential duration (APD) of canine Purkinje fibres of a therapeutic concentration of nine Class I antiarrhythmic drugs. At an extracellular K+ concentration of 5.6 mmol/L all nine agents reduced APD at all drive rates studied (range of interstimulus intervals = 200–1000 ms). At lower levels of K+, quinidine (5 μmol/L) and disopyramide (10 μmol/L) (Class Ia agents) revealed dual effects on APD. At the lowest levels of K+ (2 mmol/L) and the longest interstimulus interval used (2000 ms), both agents significantly prolonged APD. Under all other conditions, APD was either unchanged or reduced. Lignocaine, 15 μmol/L (Class Ib agent) reduced APD at all rates and all K+ concentrations and this effect was greatest at the slowest rates.2. Flecainide (1 μmol/L) (Class Ic) shortened APD at K+= 5.6 and 4 mmol/L but had no effect at K+= 2 mmol/L.3. We conclude that these data result from opposing drug actions on inward sodium and outward potassium currents flowing during the plateau of the action potential.4. Class Ia drugs exhibit significant depression of both currents, with the resultant effect on APD being modulated by external K+ concentration and drive rate.5. Class Ib agents predominantly depress the sodium current and hence shorten APD, and Ic compounds have intermediate actions.6. These differential effects on APD must be considered when planning antiarrhythmic therapy, and are directly relevant to the proarrhythmic propensities of these agents.
ACTIVATION OF Na+/H+ EXCHANGE IS UNNECESSARY IN THE INDUCTION OF c‐fos mRNA IN SERUM‐STIMULATED VASCULAR SMOOTH MUSCLE CELLS
Authors: Nabika Toru , Kobayashi Ayame , Nara Yasuo , Endo Jiro , Yamori Yukio 
Published: June 2007

SUMMARY1. The effects of extracellular Na+ concentration ([Na+]o) on serum‐stimulated c‐fos mRNA induction in vascular smooth muscle cells (VSMC) were studied to examine whether the activation of Na+/H+ exchange and the following intracellular alkalinization are necessary in the induction of c‐fos in VSMC.2. When monitored with 2′, 7′‐bis (carboxylethyl)‐5(6)‐carboxyfluorescein, the reduction in [Na+]o in HCO3−‐free buffer caused a dose‐dependent inhibition of Na+‐dependent intracellular pH recovery in acid‐loaded VSMC. In addition, serum‐stimulated intracellular alkalinization in VSMC was completely blocked by the removal of extracellular Na+.3. By contrast, c‐fos induction, quantified by slit blot hybridization of c‐fos mRNA, was not fully inhibited by the reduction of [Na+]o. Furthermore, amiloride and ethylisopropyl‐amiloride, inhibitors of Na+/H+ exchange, only partially blocked c‐fos induction by serum.4. We concluded from the observation above, that the intracellular alkalinization caused by the activation of Na+/H+ exchange was unnecessary in serum‐stimulated induction of c‐fos mRNA in VSMC.
URINARY EXCRETION OF PROSTANOIDS DURING SLEEP IN OBSTRUCTIVE SLEEP APNOEA PATIENTS
Authors: Krieger Jean , Benzoni Daniel , Sforza Emilia , Sassard Jean 
Published: June 2007

SUMMARY1. Given the unexplained frequent association between systemic hypertension and obstructive sleep apnoea (OSA), the secretion of prostanoids during sleep was investigated (more specifically, the ratio of prostacyclin (PGI2) to thromboxane A2 (TxA2), since they have marked opposite effects on vascular tone). Prostacyclin has vasodilating effects, whereas thromboxane results in vasoconstriction.2. In 11 OSA drug‐free male patients (age 53 ± 2 years, mean ± s.e.m.; apnoea index 55 ± 15 apnoeas/hour of sleep; body mass index 31 ± 2 kg/m2), we measured the urinary excretion during sleep of 6‐keto‐PGF1‐alpha and of thromboxane TxB2 (the stable metabolites of prostacyclin PGI2 and of thromboxane A2 respectively). This was done on two consecutive nights; one untreated, the other with nasal continuous positive airway pressure (CPAP) treatment. The results were compared with those of nine normal unobese male subjects.3. The urinary ratio of 6‐keto‐PGF1‐alpha to TxB2 was significantly (P<0.001) lower in the untreated OSA patients (1.7 ± 0.2) than in the controls (3.1 ± 0.3). It significantly increased with CPAP treatment to 2.3 ± 0.2, P<0.02, which was no longer different from the controls.4. These results suggest that OSA is associated with an abnormal release of prostanoids during sleep resulting in a decrease of the prostacyclin to thromboxane ratio which potentially has a vasoconstricting effect. The relationship between these changes and the systemic hypertension often observed in OSA patients remains to be established.
GENETIC FACTORS REGULATE THE RISE IN BLOOD PRESSURE IN F2 GENERATION CROSSED BETWEEN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS AND WISTAR‐KYOTO RATS
Authors: Ikeda Katsumi , Nara Yasuo , Nabica Toru , Fujimoto Akihiko , Endo Jiro , Ishino Hiroshi , Yamori Yukio 
Published: June 2007

SUMMARY1. There was no significant difference between the systolic blood pressure (SBP) of offspring derived from SHRSP mother and WKY father and the SBP of offspring derived from WKY mother and SHRSP father at the developing stage (5–13 weeks of age).2. The degree of genetic determinations of SBP in stroke‐prone spontaneously hypertensive rat (SHRSP) at 5, 7, 10 and 13 weeks of age, determined by genetic crosses between SHRSP and WKY, was 73.9, 70.8, 50.2 and 55.3% respectively.3. Significant correlations between SBP at 5 and 7 weeks, 7 and 10 weeks, 10 and 13 weeks, also at 5 and 13 weeks of age in F2 generation crossed between SHRSP and WKY were observed. SBP falling at or above the 80th percentile group in F2 generation at 5 weeks of age were constantly higher than SBP falling at or below the 20th percentile group from 7 weeks of age onwards.4. These results indicate that there exists ‘tracking phenomenon of SBP in SHRSP’ and that genetic factors regulate the rise in SBP. Tracking of SBP in F2 generation gives us new methodological insight into hypertensive mechanism in SHR.
AUTACOIDS AFFECTING VASCULAR TONE IN THE HUMAN FETAL EXTRACORPOREAL CIRCULATION
Authors: Walters William A. W. 
Published: June 2007

SUMMARY1. The human fetal extracorporeal circulation is normally a vasodilated, low pressure system.2. As this vasculature lacks innervation, autacoids have been postulated as being of great importance in controlling its tone.3. This has now been confirmed by pharmacological in vitro techniques, particularly utilizing perfusion of the isolated umbilical cord and placental lobule.4. The fetal umbilical—placental vessels are sensitive to a wide range of vasoconstrictor autacoids, some of which can cause intense vasospasm.5. Thromboxane A2 receptors have been identified in both umbilical vein and placental villous vessels.6. Prostacyclin and endothelial cell‐derived relaxing factor (or nitric oxide) may be largely responsible for the low vascular resistance normally found in the fetal extracorporeal circulation.7. Immediately after birth it is likely that stimuli such as cooling, stretching and handling of the umbilical cord cause release of eicosanoids and other autacoids from the vessels, leading to their complete closure.
CHEMICAL DESIGN OF PERIPHERALLY ACTING COMPOUNDS
Authors: Jackson W. Roy , Copp Fred C. , Cullen John D. , Guyett Frances J. , Rae Ian D. , Robinson Andrea J. , Pothoulackis Helen , Serelis Algirdas K. , Wong Margaret 
Published: June 2007

SUMMARY1. Some guanidines, related in structure to mianserin and to 2‐methyl‐1,2,9,13b‐tetrahydro‐3H‐dibenz[c,f]irnadazo[l,5a]azepin‐3‐imine hydrobromide (WAL 801), have been synthesized and shown to be peripherally acting 5‐HT2antagonists. Structurally related compounds but not bearing a charged ionic group have been shown to have central activity.2. Computer‐aided molecular modelling has been used to establish a 5‐HT2pharmacophore.3. The principle of exclusion from the CNS by incorporating a highly polar group to a biologically active molecule has been extended to the design and synthesis of a peripherally acting analgesic.
SENSORY NERVES IN THE AIRWAYS AS A TARGET FOR DRUG DEVELOPMENT
Authors: Rechtman M. P. 
Published: June 2007

SUMMARY1. Electrical stimulation (2.5–10 Hz, 80 V, 1 ms for 15 s) within the spinal canal of the pithed guinea‐pig pretreated with atropine, D‐tubocurarine and pentolinium caused a bronchoconstrictor response, indicated by a rise of insufflation pressure.2. The magnitude of these non‐cholinergic neuronal bronchoconstrictor responses were frequency‐dependent, capsaicin‐sensitive and temperature‐dependent.3. Responses could be inhibited by the α2‐adrenoceptor agonist B‐HT920 (3 mg/kg, i.v.) and the μ‐opioid agonist H‐Tyr‐D‐Arg‐Phe‐Lys‐NH2 (DALDA; 1 mg/kg, i.v.) and the attenuation observed could be overcome by use of the respective antagonists idazoxan (3 mg/kg, i.v.) and naloxone (3 mg/kg, i.v.).4. Substance P‐induced bronchoconstriction (0.3 μg/kg, i.v.), but not that due to electrical stimulation, was attenuated by indomethacin (3 mg/kg, i.v.), indicating an indirect action of substance P via a product of arachidonic acid metabolism.5. The prostanoid product of the substance P response was probably thromboxane A2.6. Hence, novel drug development could be directed towards tachykinin receptors or to the synthesis, release and degradation of neuropeptides.
AN INDUSTRIAL APPROACH TO DRUG DISCOVERY: A PHARMACOLOGIST'S EYEVIEW
Authors: Armstrong J. M. , Hicks P. E. 
Published: June 2007

SUMMARY1. The pressures on the pharmaceutical industry to produce novel, safe and effective therapeutic agents have provoked management to rethink the way in which drug discovery is undertaken.2. Advances in drug therapy are likely to come from the application of new technologies and leading‐edge science, perhaps in collaboration with academia.3. Close collaboration between biologists and medicinal chemists is a proven way to discover new products.4. The complexity of the modern industrial discovery process, due to the interaction of many disciplines, requires matrix‐style management.5. The early demonstration of efficacy in human subjects is considered essential for providing feedback to the basic scientists about the validity of hypotheses, and the relevance of the methods utilized, as well as whether a decision should be allowed to advance to full development.
ORIGIN OF URINARY EPIDERMAL GROWTH FACTOR IN HUMANS: EXCRETION OF ENDOGENOUS EGF AND INFUSED [131I]‐HUMAN EGF AND KIDNEY HISTOCHEMISTRY
Authors: Lev‐Ran Arye , Hwang David L. , Ben‐Ezra Jonathan , Williams Lawrence E. 
Published: June 2007

SUMMARY1. This study examined (i) whether blood‐infused epidermal growth factor (EGF) can pass into urine; (ii) whether infused labelled EGF behaves like endogenous plasma immunoreactive EGF; and (iii) which parts of the human nephron show morphological evidence of EGF synthesis?2. We infused human [131I]‐EGF into a volunteer. After 6 min, only 66% of the plasma counts represented intact EGF. At the end of infusion, the T 1/2 of EGF was calculated to be 1.6 min. The tail of the curve lasted for at least another 2 h. The total excretion of the labelled EGF was 2.45% of the infused dose and was proportional to the urine volume.3. After a water load, the excretion of endogenous EGF was, on the contrary, inversely related to urine volume.4. Immunohistochemically, human kidneys were not stained by monoclonal anti‐EGF antibodies but showed positive in situ hybridization for EGF mRNA in the nuclei of glomerular mesangial cells, distal convoluted tubules and collecting tubules.5. We conclude that human kidneys synthesize EGF and release it into urine. Plasma‐derived EGF constitutes under normal conditions only a small part of the urinary EGF. Contrasting volume‐dependency of the excretion of endogenous and [131I]‐EGF requires further study and cautions against extrapolating results obtained with labelled EGF to physiological conditions.
EFFECTS OF 4 WEEKS ENDURANCE TRAINING ON CARDIAC LEFT VENTRICULAR STRUCTURE AND FUNCTION
Authors: Dart Anthony M. , Meredith Ian T. , Jennings Garry L. 
Published: June 2007

SUMMARY1. The effect of 4 weeks of moderate exercise training on cardiac left ventricular structure and function was examined by repeated echocardiography/ Doppler examination in 10 previously sedentary volunteers participating in a single blind, sedentary phase controlled, cross‐over study.2. Left ventricular internal diastolic diameter increased after 4 weeks of training from 4.98 to 5.11 cm with a further increase to 5.24 cm after 2 weeks of detraining (s.e.d. 0.05 cm, P < 0.01). These increases were still significant after adjustment for heart rate which fell from a pretraining average of 67.0‐59.9 beats/min after 4 weeks of training.3. There were no significant changes in systolic diameter or function and left ventricular wall thicknesses were unchanged during training, but were thinned after 2 weeks subsequent detraining.4. The ratio of early to late transmitral filling velocity (E/A ratio) was significantly increased by training. Although E/A ratio was shown to be heart rate sensitive, training effects were still evident after adjustment for heart rate.5. These changes in left ventricular volumes and function may contribute to the cardiovascular reflex changes previously shown to be produced by identical training programmes.
POTASSIUM ACCELERATES URINARY SODIUM EXCRETION DURING SALT LOADING WITHOUT STIMULATING ATRIAL NATRIURETIC POLYPEPTIDE SECRETION
Authors: Mano Masayuki , Sugawara Akira , Nara Yasuo , Nakao Kazuwa , Horie Ryoichi , Endo Jiro , Imura Hiroo , Yamori Yukio 
Published: June 2007

SUMMARY1. Effects of potassium (K) supplementation (100 mEq/day) on urinary sodium (Na) excretion and on the secretion of atrial natriuretic polypeptide (ANP) during salt loading (350 mEq/day) were studied in 12 healthy salt‐resistant normotensives under strictly controlled metabolic ward conditions.2. Urinary volume and Na excretion on the first day of the high salt period (HSP) were significantly greater in the K‐supplemented group (KG) than in the control group (CG).3. There was a significant gain in bodyweight after salt loading in both groups, with a significantly greater gain in CG on the second day of HSP. Haematocrit decreased significantly during salt loading in both groups, the degree of which was significantly greater in CG.4. Plasma norepinephrine decreased significantly during salt loading in both groups, the degree of which was significantly less in KG than in CG. A significant increase in plasma ANP was observed in CG on and after the second day of HSP, while a significant increase in plasma ANP was observed on the fifth day of HSP in KG.5. These findings indicate that K supplementation accelerates diuresis and natriuresis, resulting in moderate suppression of volume expansion induced by salt loading and that this accelerated diuresis and natriuresis is not a result of the action of ANP.
ASSESSING VASCULAR REACTIVITY OF ARTERIES IN THE SMALL VESSEL MYOGRAPH
Authors: McPherson Grant A. 
Published: June 2007

SUMMARY1. Using a small vessel myograph, experiments were performed on rat small mesenteric arteries (and in some cases dog small coronary arteries) to assess the dependence of vasoconstrictor potency (EC50) and maximum response (Emax) on the initial passive conditions and on the mode of recording (i.e. isometric, isobaric or isotonic).2. Maximum active isometric tension development to methoxamine occurred at different points on the passive diameter‐tension curve depending on the origin of the vessel. The point of maximum sensitivity of methoxamine did not coincide with the point of maximum tension development on the passive diameter‐tension curve.3. Vascular reactivity to methoxamine was assessed under isobaric, isotonic and isometric conditions using a new computerized myograph. Methoxamine was significantly more potent, but only by a factor of twofold, when assessed under isometric conditions. In addition, the maximum response to methoxamine, in terms of diameter change, was always greater under isobaric than under isotonic conditions.4. The results show that, in studies comparing vascular reactivity of vasoactive drugs, the results depend, to some extent, on the initial passive conditions selected. In terms of assessing the pharmacological activity of drugs on isolated blood vessels, the use of common isometric recording procedures are adequate. However, the use of isobaric, isotonic and isometric recording procedures have shown the complexities of vascular reactivity which depend on the passive and active properties of the blood vessel. These factors may need to be taken into account when comparing the reactivity of isolated blood vessels.
CYCLIC ADENOSINE 3′,5′‐MONOPHOSPHATE CONTENT AND BRONCHIAL SMOOTH MUSCLE CONTRACTILITY OF HYPER‐ AND HYPOTHYROID LUNGS
Authors: Nabishah B. M. , Morat P. B. , Alias A. K. , Kadir B. A. , Khalid B. A. K. 
Published: June 2007

SUMMARY1. Male Sprague‐Dawley rats were made either hyper‐ or hypothyroid with thyroxine or 4‐methyl‐2‐thiouracil, respectively. Bronchial smooth muscle (BSM) contractility and lung cyclic adenosine 3′,5′‐monophosphate (cAMP) content were measured in both conditions.2. Bronchial smooth muscle contractility was significantly weaker in hyperthyroid rats, while the BSM contractility of hypothyroid rats was the same as controls.3. The cAMP content of hyperthyroid rat lungs was similar to controls but was decreased in hypothyroid rats.4. These studies demonstrated that both the hyper‐ and hypothyroid states affect respiration, although the mechanisms involved with different for each condition.
IMPEDANCE MEASUREMENT DURING AIR AND HELIUM‐OXYGEN BREATHING BEFORE AND AFTER SALBUTAMOL IN COPD PATIENTS
Authors: Wouters E. F. M. , Lándsér F. J. , Polko A. H. , Visser B. F. 
Published: June 2007

SUMMARY1. The forced oscillation technique is an effort‐independent method used to characterize the mechanical impedance of the respiratory system. To support the hypothesis that non‐invasive partitioning of total pulmonary resistance is possible by this technique, impedance was measured during air breathing and after equilibration with a mixture of 80% helium (He) and 20% oxygen (O2) in 21 chronic obstructive pulmonary disease (COPD) patients by means of a forced pseudo‐random noise pressure signal over a frequency spectrum from 4 to 52 Hz. Furthermore, during inhalation of both gas mixtures impedance was determined before and after inhalation of 0.400 mg Salbutamol.2. He + O2 breathing caused less negative frequency dependence of resistance and a significant decrease in reactance over the range 16–52 Hz. Inhalation of Salbutamol caused a marked increase in reactance values over the range 8–40 Hz. However after equilibration with the He + O2 mixture, Salbutamol caused a significant decrease in resistance and a significant increase in reactance at all frequencies.3. The results during He + O2 breathing are in accordance with a partitioning of airways resistance into central and peripheral components. The decrease in reactance during He + O2 can be explained by a density dependent decrease in inductive reactance. By comparing the impedance data during air and He + O2 breathing, it can be concluded that a distribution of pulmonary resistance with minimal losses in the larger airways is more sensitive for detecting changes in the peripheral airways in COPD patients.
PLASMA PHOSPHOLIPASE A2 ACTIVITY IN CLINICAL ACUTE MYOCARDIAL INFARCTION
Authors: Leong Lillian L. L. , Sturm Marian J. , Ismail Yahya , Stephens Charlene J. , Taylor Roger R. 
Published: June 2007

b1. Phospholipase A2 (PLA2) cleaves phospholipids to produce a lyso‐phospholipid and free fatty acid and, in view of the biological activity of the products, PLA2 may play a role in many disease states. Lyso‐phospholipids and free arachidonic acid increase in ischaemic myocardium, indicating that ischaemia activates the enzyme.2. Plasma PLA2 activity was measured in patients with acute myocardial infarction, based on the release of labelled arachidonic acid from Escherichia coli cell membrane. Fourteen males (peak serum creatine phosphokinase (CK) above twice upper normal) were studied on day 1 (within 6 h of chest pain onset), days 2–4, and days 6–9. Normal age matched males (n= 13) were also studied.3. Plasma PLA2 in patients with uncomplicated myocardial infarction (n= 12) was, initially, 1.14±0.10 (s.e.m.) nmol/min per mL plasma, similar to that in the normal group (1.52 ± 0.14). On days 2–4, PLA2 activity increased to 1.94±0.18(P<0.001) and this activity was correlated with the earlier peak CK level (P<0.02). On days 6–9, PLA2 activity was 1.49±0.13 while in two patients who developed complications and underwent open‐heart surgery between the last two measurements, there were further increases to 4.22 and 4.04 nmol/min per mL.4. The increase in plasma PLA2 in uncomplicated myocardial infarction is likely to be due to release from the damaged myocardium; whether it contributes to pathophysiology is uncertain.
SUPEROXIDE DISMUTASE ATTENUATED POST‐ISCHAEMIC CONTRACTILE DYSFUNCTION IN A MYOCARDIAL XANTHINE OXIDASE DEFICIENT SPECIES
Authors: Ooiwa Hitoshi , Miura Tetsuji , Iwamoto Toshihiro , Ogawa Takashi , Ishimoto Row , Adachi Takeo , Iimura Osamu 
Published: June 2007

SUMMARY1. We assessed the effect of polyethylene glycol conjugated superoxide dismutase (PEG‐SOD) on myocardial stunning in the rabbit heart in which xanthine oxidase level is extremely low.2. In open‐chest anaesthetized rabbits, the left marginal branch of the coronary artery was occluded for 10 min and then reperfused for 30 min. A group of rabbits (PEG‐SOD group) received 1000 units/kg of PED‐SOD and another group (control group) was given saline 15 min before the coronary occlusion.3. Regional systolic thickening fraction (TF) was similarly reduced to approximately ‐ 25% of baseline value during ischaemia in both groups. However recovery of TF after reperfusion was significantly better in the PEG‐SOD group (n= 9) and TF at 30 min after reperfusion was 70.1 ±3.9% of baseline value compared with 44.9 ±3.4% in the control group (n= 9; P < 0.05). Rate‐pressure products, left ventricular pressure, and LV dP/dt max were not significantly different between the PEG‐SOD treated and untreated control rabbits at any time during the experiment. PEG‐SOD did not modify the regional myocardial blood flow (coloured microsphere method) during ischaemia/reperfusion, which was assessed by using separate groups of rabbits.4. These findings indicate that oxygen free radicals are important in the pathogenesis of myocardial stunning in xanthine oxidase deficient hearts.