bluuebunny/crossref_metadata_2025_split huggingface dataset:
ENDOTHELIUM‐DERIVED HYPERPOLARIZING FACTOR
Authors: Félétou Michel , Vanhoutte Paul M. 
Published: June 2007

SUMMARY1. Not all endothelium‐dependent relaxation can be full explained by the release of either nitric oxide (NO) and/or prostacyclin. Another unidentified substance(s) that hyperpolarizes the underlying vascular smooth muscle cells (endothelium‐derived hyperpolarizing factor; EDHF) contributes to endothelium‐dependent relaxations.2. In blood vessels from various species these hyperpolarizations are resistant to inhibitors of NO synthase (NOS) and cycl‐oxygenase. In canine, porcine and human blood vessels the hyperpolarization cannot be mimicked by nitrovasodilators or exogeneous NO. However, in other species (rat, guinea‐pig, rabbit) endothelium‐dependent hyperpolarizations resistant to inhibitors of NOS and cyclo‐oxygenase and hyperpolarizations to endothelium‐derived or exogeneous NO can be obsercved n the same vascular smooth muscle cells.3. In blood vessels where NO causes hyperpolarization, the response is blocked by glibenclamide, suggesting the involvement of ATP‐dependent potassium channels. Hyperpolarizations caused by EDHF are insensitive to glibenclamide but, depending on the tissue, are inhibited by relatively small concentrations of tetraethylammonium (TEA) or by apamin or the combination of charybdotoxing plus apamin, indicating that calcium‐dependent potassium channels are likely to be involved.4. Metabolites of arachidonic acid, through the cytochrome P450 mono‐oxygenase pathway (epoxyeicosatrienoic acids), are produced by the endothelial cells, increase the open‐state probability of calcium‐activated potassium channels sensitive to TEA or charybdotoxin, and induce the hyperpolarization of arterial smooth muscle cells, indicating that epoxyeicosatrienoic acids could be EDHF. However, in blood vessels from various species, cytochrome P450 inhibitors do not affect endothelium‐dependent hyperpolarizations, indicating that EDHF is not yet identified with certainty.5. Endothelium‐derived hyperpolarizing factor released from cultured endothelial cells reduces the intracellular calcium concentration in vascular smooth muscle cells and the EDHF component of the relaxation is proportionally more important in smaller than larger arteries. In aging animals and in various models of diseases, endothelium‐dependent hyperpolarizations are diminished.6. The identification of EDHF and/or the discovery of specific inhibitors of its synthesis and its action may allow a better understanding of its physiological and pathophysiological role(s).
REGULATION AND ROLE OF UROKINASE PLASMINOGEN ACTIVATOR IN VASCULAR REMODELLING
Authors: Tkachuk Vsevolod , Stepanova Victoria , Little Peter J. , Bobik Alex 
Published: June 2007

SUMMARY1. Urokinase plasminogen activator (uPA) is produced and secreted by multiple vascular cell types, thus influencing the processes and the extent to which the vasculature is remodelled during the development of the intima or a neointima and during hypertrophy and angiogenesis.2. Urokinase plasminogen activator mRNA expression is up‐ and down‐regulated by growth factors, cytokines and steroids. Urokinase plasminogen activator is secreted as a single chain inactive form that may be proteolytically converted to active or inactive forms. Targeting of proteolytic activity may occur via focalized expression of uPA and its cell surface receptors (uPAR). Proteolytic activity is also controlled through the often co‐ordinated expression of specific inhibitors.3. A proteolytic cascade involving uPA provides its major role in tissue remodelling through the primary degradation of extracellular matrix and secondarily through the activation of transforming growth factor‐β or release from the matrix of basic fibroblast growth factor. In addition, uPA secreted by growth factor‐stimulated vascular cells may contribute to the chemotactic and mitogenic responses ascribed to the growth factor and recent evidence strongly suggests that uPA has direct biological actions on vascular cells.4. The cell surface binding of uPA via its growth factor‐like domain to uPAR localizes and activates the protease, but may also initiate transmembrane signalling of biological responses, including migration/invasion and proliferation. As the uPAR lacks intracellular signalling domains, the signals may be transduced via interactions between uPA/uPAR and more classical signalling receptors. The mechanism by which uPA may be involved in cell signalling is yet to be elucidated.
DIRECT MEASUREMENT OF THE RELEASE OF ATP AND ITS MAJOR METABOLITES FROM THE NERVE FIBRES OF THE GUINEA‐PIG TAENIA COLI
Authors: McConalogue K. , Todorov L. , Furness JB , Westfall DP 
Published: June 2007

SUMMARY1. The release of adenosine triphosphate (ATP), adenosine diphosphate, adenosine monophosphate and adenosine from guinea‐pig taenia coli in response to electrical stimulation of intramural nerves was measured directly using high performance liquid chromatography separation and fluorometric detection.2. Purines were released in a frequency‐dependent manner by trains of transmural electrical pulses at 1‐30 Hz.3. Electrically evoked release of ATP was abolished by tetrodotoxin (10−6 mol/L) but was not affected by nicardipine (10−6 mol/ L).4. The release of purines was reduced in the presence of atropine.5. Pituitary adenylyl cyclase‐activating peptide did not evoke the release of any purines and did not modify the electrically evoked release of purines.6. The results suggest that ATP and its major metabolites are released from a neuronal source, possibly the enteric inhibitory nerves, in the guinea‐pig taenia coli.
TACHYCARDIA AFTER GLUTAMATE INJECTION IN RAT SPINAL CORD IS NOT BLOCKED BY KYNURENATE OR MIMICKED BY METABOTROPIC AGONISTS
Authors: Arnolda Leonard F. , Pilowsky Paul M. , Minson Jane B. , Llewellyn‐Smith Ida J. , Chalmers John P. 
Published: June 2007

SUMMARY1. We have used microinjections of glutamate, an ionotropic excitatory amino acid receptor antagonist (kynurenate) and selective ionotropic (NMDA and kainate) and metabotropic (lS‐3R‐ACPD, trans‐ACPD and L‐AP4) receptor agonists in the thoracic IML of the rat to define the receptors mediating the tachycardia produced by excitatory amino acid agonists.2. Injection of glutamate (Δ heart rate = 76±8 beats/min n = 16), NMDA (A heart rate = 116.5±5 beats/min n = 6) or kainate (Δ heart rate = 92±22 beats/min n = 6) evokes a tachycardia when injected into the thoracic intermediolateral column. Kynurenate blocked the response to NMDA (‐2% of initial response) and markedly attenuated the response to kainate (14% of initial response) but did not alter the response to glutamate (106% of initial response).3. IS‐3R‐ACPD did not elicit a tachycardia when injected into the thoracic intermediolateral column and neither trans‐ACPD nor L‐AP4 induced a tachycardia after kynurenate injection into the thoracic intermediolateral column.4. Thus stimulation of either NMDA or AMPA/kainate receptors elicits a tachycardia in rat thoracic spinal cord but glutamate also activates another receptor type to elicit a tachycardia. The lack of a tachycardia when trans‐ACPD1, 1S‐3RACPD or L‐AP4 were injected into the thoracic spinal cord suggests that the kynurenate resistant tachycardia elicited by glutamate is not mediated by metabotropic receptors. The kynurenate resistant tachycardia elicited by glutamate is not mediated by any of the known excitatory amino acid receptor types.
ON THE ANTIARRHYTHMIC ACTIONS OF MAGNESIUM IN SINGLE GUINEA‐PIG VENTRICULAR MYOCYTES
Authors: Song Yejia , Liu Qi‐Ying , Vassalle Mario 
Published: June 2007

SUMMARY1. The hypotheses that magnesium quickly abolishes arrhythmias by acting as a calcium antagonist or by increasing outward potassium currents were tested in guinea‐pig isolated ventricular myocytes by recording membrane potentials and currents by means of a single microelectrode discontinuous voltage clamp method.2. High [Mg2+]0 (4‐16 mmol/L) slightly increased the amplitude and duration of the action potential (AP) in some myocytes, but overall the changes were not significant.3. High [Mg2+]0 did not decrease the slow inward current (Ica) and had little effect on voltage‐ and time‐dependent outward potassium currents whether or not Ica was allowed to flow.4. Zero [Mg2+]0 decreased the duration, but not amplitude, of the AP. Zero [Mg2+]0 had little effect on Ica and on outward currents except for a small increase in outward current in the region of the negative slope of the inward rectifier currentvoltage relationship.5. In our myocytes, in contrast to [Mg2+]0 high [Ca2+]0 significantly increased the amplitude and decreased the duration of the AP; at the same time, high [Ca2+]0 increases Ic2. and the outward potassium current.6. High [Mg2+]0 decreased the amplitude of the oscillatory potentials (Vos) induced by various Ca2+‐over1oading procedures (high [Ca2+]0, noradrenaline, strophanthidin and barium).7. It is concluded that the mechanisms by which high [Mg2+]0 quickly suppresses cardiac arrhythmias are related to an extracellular action of Mg2+ and do not include a block of ICa, or an increase in outward current. Mg2+ can be antiarrhythmic by decreasing Vos amplitude and possibly by screening the fixed negative charges at the external surface of the sarcolemma.
POSSIBLE INVOLVEMENT OF MUSCARINIC M1 AND M3 RECEPTOR SUBTYPES MEDIATING VASODILATION IN ISOLATED, PERFUSED CANINE LINGUAL ARTERIES
Authors: Chiba Shigetoshi , Tsukada Miyoko 
Published: June 2007

SUMMARY1. Using the cannula insertion method, muscarinic receptor subtypes were analysed in isolated, perfused canine lingual arteries preconstricted with phenylephrine.2. Both acetylcholine and McN‐A‐343 induced a profound vasodilation in a dose‐related manner. Acetylcholine‐induced dilations were approximately 1000‐times more potent than McN‐A‐343‐induced dilation.3. Acetylcholine‐induced dilations were abolished after removal of the endothelium by intraluminal treatment with 1 mg saponin.4. Acetylcholine‐induced dilations were markedly inhibited by an M1/M3 receptor antagonist, 4‐DAMP. Moreover, they were slightly, but significantly, inhibited by an M1 antagonist, pirenzepine, but never influenced by an M2 antagonist, AF‐DX 116. Mc‐N‐A‐343‐induced vasodilations were inhibited by both 4‐DAMP or pirenzepine.5. These results suggest that there are abundant functional M3 and a few M1 receptors in the canine lingual artery that mediate vasodilation and that this vasodilation is dependent on the presence of an intact endothelium.
MECHANISMS OF MYOCARDIAL PROTECTION BY AMINO ACIDS: FACTS AND HYPOTHESES
Authors: Pisarenko Oleg I. 
Published: June 2007

SUMMARY1. Positive inotropic effect of taurine and improvement of cardiac performance of failing heart are mediated through the modulation of Ca2+ movement through the sarcolemma.2. Cardioprotection with glutamate and aspartate is related to enhanced anaerobic energy formation in mitochondria coupled with succinate formation and, probably, with the relieving of glycolytic flux. During reperfusion, both amino acids replenish the malate‐aspartate shuttle reactants, thereby facilitating glucose oxidation.3. Increased intracellular concentrations of branched chain amino acids (leucine, valine and isoleusine) stimulate formation of acetyl‐coenzyme (CoA) and succinyl‐CoA and, thus, recovery of oxidative metabolism.4. Methionine and cysteine enhance force of contraction by N‐methylation of membrane phospholipids of the sarcolemma and sarcoplasmic reticulum. Methionine and, to a lesser extent, cysteine may reduce myocardial damage by oxygen radical species.5. Histidine exerts antioxidant properties as a scavenger of singlet oxygen and OH’ radicals. High concentrations of histidine provide intracellular buffering to stimulate anaerobic energy formation.
AUGMENTED ENDOTHELIUM‐DEPENDENT CONSTRICTION TO HYPOXIA EARLY AND LATE FOLLOWING REPERFUSION OF THE CANINE CORONARY ARTERY
Authors: Pearson Paul J. , Lin Pyng J. , Schaff Hartzell V. , Vanhoutte Paul M. 
Published: June 2007

SUMMARY1. Canine coronary arteries with intact endothelium respond to hypoxaemia or serotonin infusion with dilatation, but when the endothelium is injured or dysfunctional, these stimuli can cause constriction. The present studies investigated whether or not regional ischaemia and reperfusion alter endotheliumdependent responsiveness of canine coronary arteries in vivo and in vitro.2. In organ chamber experiments, isolated control and reperfused coronary artery rings were contracted with prostaglandin F2α and exposed to hypoxia (PO2 less than 5 mmHg).3. Hypoxia augmented the response of reperfused arteries more than that of controls. The hypoxic augmentation was blocked by NG‐monomethyl‐L‐arginine, an inhibitor of nitric oxide synthesis from L‐arginine.4. These findings demonstrate that early following coronary reperfusion the hypoxic augmentation, which is mediated by a nitric oxide‐dependent pathway in the endothelium, is facilitated.5. In vivo studies revealed hyperconstriction of reperfused arteries in response to hypoxaemia (PO2= 30‐40 mmHg) and administration of either serotonin or ergonovine.6. Twelve weeks following reperfusion injury, coronary arteries still exhibited augmented endothelium‐dependent hypoxic augmentations in vitro, which were inhibited by NG‐monomethyl‐L‐arginine.7. Furthermore, resting coronary segments with endothelium displayed hypoxia‐induced contractions that could not be inhibited by indomethacin, the lipoxygenase inhibitor AA861, superoxide dismutase plus catalase, deferoxamine, ouabain, or NG‐monomethyl‐L‐arginine.8. These endothelium‐dependent hypoxic response may play a role in the pathogenesis of hyperconstriction (vasospasm) following coronary reperfusion.
EFFECTS OF TETRANDRINE AND CLOSELY RELATED BIS‐BENZYLISOQUINOLINE DERIVATIVES ON CYTOSOLIC Ca2+ IN HUMAN LEUKAEMIC HL‐60 CELLS: A STRUCTURE‐ACTIVITY RELATIONSHIP STUDY
Authors: Leung Yuk‐Man , Berdik Mariana , Kwan Chiu‐Yin , Loh Tatt‐Tuck 
Published: June 2007

SUMMARY1. Previously it has been shown that tetrandrine (TET), a bis‐benzylisoquinoline alkaloid, isolated from a Chinese herb Stephania tetrandra, can block non‐voltage‐operated Ca2+ entry activated by intracellular Ca2+ store depletion induced by thapsigargin (TSG) and can release intracellular Ca2+ in HL‐60 cells. The present study attempted to identify the chemical group(s) of the TET molecule responsible for these dual effects. The effects of TET and its closely related analogues, hernandezine (HER) and berbamine (BER), on Ca2+ entry and Ca2+ release were compared in fura‐2‐loaded HL‐60 cells.2. Berbamine was much less potent (IC50= 200 μmol/L) than TET and HER (both IC50 values = 25 μmol/L) in inhibiting Ca2+ entry activated by TSG. Furthermore, at 100 μmol/L, BER was much less effective than TET and HER in suppressing TSG‐induced Mn2+ entry. At 30‐100 μmol/L, BER was significantly less effective than both TET and HER in causing Ca2+ release from internal stores. However, only BER was able to cause store depletion‐activated Ca2+ entry (or the so‐called ‘capacitative Ca2+ entry') upon Ca2+ readmission.3. Taken together, the data from this structure‐activity relationship study reveal that the‐OCH3 group of one particular benzene ring of TET, which distinguishes TET from BER, in part produces the dual pharmacological actions of TET.
EFFECTS OF FULLER'S EARTH AND ACTIVATED CHARCOAL ON ORAL ABSORPTION OF PARAQUAT IN RABBITS
Authors: Idid SZ , Lee CY 
Published: June 2007

SUMMARY1. Thirty male rabbits of local strain (weighing 1.5‐2kg) were divided into five groups. Four groups were treated with an oral dose of paraquat, which was followed by either Fuller's Earth or activated charcoal 0.5 or 2.0 h later. The remaining group acted as the control group and was treated only with an oral dose of paraquat. The dose of paraquant was 20.0 mg/kg given in a concentration of 20.0 mg/mL.2. Both adsorbents were administered in 15mL normal saline as a 30% slurry. Blood was sampled from the ear vein 0.5, 1, 2, 4, 8 and 24 h after the administration of paraquat.3. Paraquat concentration was determined spectophotometrically at 600 nm by comparing against a standard curve of paraquat obtained by the addition of standard paraquat into normal rabbit serum and extracting interfering substances with ether.4. The results of the present study show that either adsorbent can bring down the serum paraquat level. There was no significant difference found in the effectiveness of either adsorbent.5. It is concluded that the administration of an adsorbent as early as possible will help in the reduction of paraquat absorption from the gastrointestinal tract.6. Activated charcoal is still effective in lowering serum paraquat concentration when given more than 1 h after ingestion of paraquat.
CHANGES IN RENAL RENIN GENE EXPRESSION IN FETAL SHEEP†
Authors: Zhang David Yanling , Lumbers Eugenie R. , Simonetta Giuseppe 
Published: June 2007

SUMMARY1. Renin gene expression was investigated in kidneys from 13 foetal and four adult sheep.2. The levels of renal renin and mRNA in foetuses were greater than those in adult sheep (P < 0.001).3. There was no significant difference in renin mRNA levels between foetuses aged 91 and 134 days (term 150 days).4. The levels of renin gene expression were higher (178±5 units; P < 0.001) in foetuses at 142 days than levels in 91 (144±4 units) and 134 days old foetuses (146±6 units).5. It is concluded that the high level of renin gene expression in the foetal kidney in responsible for the high levels of renin in the foetal circulation.
SILENT AFFERENTS: A SEPARATE CLASS OF PRIMARY AFFERENTS?
Authors: Michaelis M. , Häbler H‐J , Jänig W. 
Published: June 2007

SUMMARY1. In recent years, fine sensory nerve fibres have been detected that are not excited by physiological stimuli, even at potentially tissue damaging intensities. These silent afferents are known to supply knee joint, skin and viscera; in the last case, silent afferents seem to be particularly numerous.2. When an artificial inflammation is induced, many silent afferents develop spike activity, others remain quiescent. Silent afferents that do respond probably have a nociceptive sensory function. Under inflammatory conditions some silent afferents are sensitized to physiological stimuli, others are probably chemospecific.3. Orthodromic activity in silent afferents may sum spatially and temporally in second order neurons with other nociceptive information and may thereby contribute to different pain states. Furthermore, there is evidence that the activation of chemospecific silent afferents may lead to sensitization of nociceptive dorsal horn neurons.4. Some silent afferents probably contain neuropeptides that may be liberated under pathophysiological conditions, such as inflammation.5. Whether certain pathological states can be exclusively attributed to the activation of silent afferents or whether silent afferents sustain the functions of ‘conventional’ nociceptors remains to be clarified.
VALIDATION OF A SUBENDOCARDIAL ISCHAEMIC SHEEP MODEL BY INTRACORONARY FLUORESCENT MICROSPHERES
Authors: Li DS , Yong AC , Kilpatrick D. 
Published: June 2007

SUMMARY1. We evaluated the use of non‐radioactive fluorescent‐labelled microspheres (FM) for the measurement of regional myocardial blood flow (RMBF) in an ischaemic sheep model.2. Injection of FM directly into the coronary artery was compared with left atrial injection. There was a good correlation in the measurement of RMBF between these two injection methods (r = 0.92; n= 107 data points). Injection into the coronary artery requires less FM (one twentieth of that required by atrial injection) and is more economical.3. The use of a fluorescent technique without filtering myocardial tissue was investigated. Calibration curves from the fluorescence plus myocardial tissue samples were similar to those of the pure fluorescence samples and both showed a linear relationship between fluorescent intensity and the number of microspheres (r > 0.97). These results indicate that the extraction of six fluorescent dyes (blue‐green, yellow‐green, green, orange, red and crimson) directly from the aqueous solution using ethyl acetate is effective.4. A subendocardial ischaemic model was produced by partially occluding the circumflex artery (CxA) with concomitant left atrium (LA) pacing. During ischaemia, the endocardium/epicardium (Endo/Epi) flow ratios in the ischaemic area changed from 1.04 ± 0.12 to 0.47 ± 0.17 (P < 0.05; CxA injection) and from 1.08 ± 0.12 to 0.51 ± 0.05 (P < 0.05; LA injection). The ratio in the non‐ischaemic area remained unchanged (1.12 ± 0.26 to 1.01 ± 0.22; not significant).5. RMBF calculation using coronary inflow as the reference flow was also compared with that using the traditional method. We found that, in this study in which a non‐filtering technique was applied, using coronary inflow as the reference flow was superior to the conventional distal sampling method.
TACHYKININ RECEPTORS AND NON‐CHOLINERGIC BRONCHOCONSTRICTION IN THE ANAESTHETIZED GUINEA‐PIG
Authors: Yuan Liqun , Burcher Elizabeth , Nail Bruce 
Published: June 2007

SUMMARY1. Bronchoconstriction can be evoked by electrical stimulation of the vagus nerves in the presence of atropine. We have used novel, highly selective tachykinin receptor antagonists, together with a procedure for on‐line, breath‐by‐breath analysis of total lung resistance (Rl, subtractor method) and dynamic lung compliance (Cdyn), to investigate the role of tachykinins in this response in anaesthetized, paralysed guinea‐pigs.2. In the presence of 1 mg/kg phosphoramidon (a neutral endopeptidase inhibitor), CP 96345 (the non‐peptide NK1 selective antagonist) at 200 nmol/kg had no effect on the increase in Rl caused by vagal stimulation, but significantly inhibited the associated decrease in Cdyn.3. The NK2 selective antagonist, MDL 29913 (1 μmol/kg), significantly antagonized the changes in both Rl and Cdyn. In the absence of phosphoramidon, MDL 29913 again significantly inhibited the changes in Rl and Cdyn, although CP 96345 no longer had any effect.4. The non‐peptide NK2 selective antagonist, SR 48968 (100 nmol/kg), also effectively inhibited the responses to vagal stimulation and was more potent than MDL 29913.5. These results emphasize the importance of the NK2 receptor system in mediating non‐cholinergic bronchoconstriction evoked by vagal stimulation in the guinea‐pig.