bluuebunny/crossref_metadata_2025_split huggingface dataset:
AUTONOMIC CONTROL OF BRONCHIAL CIRCULATION IN AWAKE SHEEP DURING REST AND BEHAVIOUR
Authors: Mcllveen Stephen , White Saxon , Parsons Gibbe 
Published: June 2007

SUMMARY1. We tested the hypothesis that the pattern and the intensity of autonomic mechanisms causing vasoconstriction in the resting bronchial circulation of awake dogs also exists in awake sheep. It was also postulated that sighing behaviour and the associated bron‐chovascular dilatation induced by non‐adrenergic, non‐cholinergic (NANC) mechanisms observed in the dog exist in sheep.2. Bronchial arterial blood flow to lower airways of both lungs of awake sheep was measured continuously using pulsed Doppler flow probes mounted on the bronchial artery at prio. thoracotomy.3. Cumulative and factorial analysis of responses to randomized combinations of autonomi. α1‐, α2‐, β1‐ and β2‐adrenoceptors and cholinoceptor autonomic blockade suggests that resting vasoconstrictor activity is less in sheep than in dogs. At normal aortic pressure, the autonomic activity of these receptor groups in the sheep lowers bronchial blood flow and conductance by 30%, whereas in the awake dog, the corresponding autonomic effect is 50%.4. Tonic autonomic control of bronchial conductance can be partitioned in sheep to show significant and separat. α‐ and β‐adrenoceptor vasoconstrictor activity at a ratio of 1.8:1, an effect normally offset by a weaker vasodilator α‐/β‐adrenoceptor interaction. In contrast to the situation in awake dogs, cholinoceptors do not play a role in awake sheep.5. Nitric oxide (NO) synthase inhibition in sheep using NG‐nitro‐L‐arginine following blockade of α‐ and β‐adrenoceptors and cholinoceptors causes hypertension, but minor changes, if any, in pulmonary pressures or heart rate. Bronchial flow and conductance, however, fall from a higher resting conductance by approximately 50%, suggesting that, normally, resting bronchial flow conductance is dominated by strong tonic NO vasodilator effects that interact with weaker tonic autonomic vasoconstrictor effects.6. Superimposed (respiratory) behaviours of sighing, sneezing and coughing, which involve negative swings in intrathoracic pressure and the movement of inspired air, evoke large active bronchovascular dilator effects. These appear to be largely NANC in origin and appear to be dependent, in part, on mechanisms associated with NO release. It is postulated that the C‐fibre axon reflex using substance P, calcitonin gene‐related peptide and neurokinin A may be involved. Vocalization and eructation do not evoke bronchovascular effects.
PROSTANOID ACTION ON THE HUMAN PULMONARY VASCULAR SYSTEM
Authors: Jones Robert L. , Qian Yue‐ming , Wong Henry NC , Chan Ho‐wai , Yim Anthony PC 
Published: June 2007

SUMMARY1. Four types of prostanoid receptor are present on pulmonary arterial vessels of man. Thromboxane (TP) receptors mediate constriction and are blocked by antagonists such as BAY u‐3405, GR 32191 and EP169. Prostaglandin (PG) EP3 receptors also mediate constriction, the agonist potency ranking being SC 46275 > sulprostone > misoprostol≥PGE2; this action needs to be borne in mind when PGE analogues are used therapeutically.2. Prostaglandi. E2 causes relaxation in a few pulmonary artery preparations: an EP2 receptor may be involved. Prostacyclin, acting through IP receptors, consistently produces relaxation and studies are in progress to determine the contribution made by K+‐channel opening. Agonist potencies of stable prostacyclin analogues and non‐prostanoid prostacyclin mimetics, such as BMY 45778 and the novel diphenylindole CU 23, on human pulmonary artery and platelets are well correlated. Interestingly, the non‐prostanoid mimetics show persistent relaxant effects in vitro, which may be related to their high lipophilicities.3. Prostacyclin and iloprost are being used to treat severe pulmonary hypertension; further study of the pharmacodynamic and pharmacokinetic properties of other IP receptor agonists could produce improve. therapy.
ELECTRICAL REMODELLING OF CHRONIC ATRIAL FIBRILLATION
Authors: Lau Chu‐Pak , Tse Hung‐Fat 
Published: June 2007

SUMMARY1. It is now recognized that atrial fibrillation (AF) is not a benign condition, as it is associated with a 40% increase in mortality and a doubling of the risk of stroke.2. The development of AF leads to mechanical, electrophysiological and cellular changes in the atria that tend to sustain AF. This process is known as atrial remodelling.3. The three electrophysiological elements in the atria that initiate and sustain AF are: (i) shortening of the refractory period and an increase in dispersion; (ii) slowing of conduction velocity; and (iii) the presence of triggerin. foci.4. As AF is a heterogeneous disorder, therapeutic strategies include the use of devices (pacemakers and atrial defibrillators), radiofrequency ablation (focal ablation or the creation of linear lines) and drug therapy that may reverse a remodelle. atrium.
EFFECT OF CATIONIC DRUGS ON THE RENAL SECRETION OF RANITIDINE IN THE RAT ISOLATED PERFUSED KIDNEY
Authors: Nation Roger L. , Evans Allan M. , Cabot Juanita L. , Shanahan Kathryn M. , Hsyu Poe‐Hirr 
Published: June 2007

SUMMARY1. The rat isolated perfused kidney (IPK) was used to determine whether the renal tubular secretion of ranitidine is influenced by clinically relevant concentrations of other organic cationic drugs (amantadine, pseudoephedrine, triamterene and trimethoprim) that also undergo tubular secretion.2. Ranitidine and [3H]‐ranitidine were administered to the recirculating perfusion medium as a loading dose followed by a constant infusion to maintain clinically relevant perfusate ranitidine concentrations in the range 400–700 ng/mL. The renal clearance of ranitidine (CLR) was calculated, as was glomerular filtration rate (GFR), from the renal clearance of [14C]‐inulin.3. A total of 20 perfusions were performed and, in each case, ranitidine was administered for 80 min. In four control IPK, no drug other than ranitidine was administered. In the remaining IPK, amantadine, pseudoephedrine, triamterene or trimethoprim (n= 4 in each case) were administered to achieve low, medium and high concentrations during the 20–40, 40–60 and 60–80 min periods, respectively.4. The mean (± SD) unbound fraction of ranitidine in the perfusion medium was 0.889±0.046 and was not altered (P>0.05) by the presence of the other drugs.5. The CLR/GFR ratio for ranitidine in all kidneys was substantially greater than unity and had a mean value of 10.65 or greater in control kidneys, indicating extensive net tubular secretion.6. The CLR/GFR was not affected (P>0.05) by amantadine, pseudoephedrine or triamterene at any concentration or by trimethoprim at the low concentration. However, medium (2000 ng/mL) and high (5000 ng/mL) concentrations of trimethoprim caused significant reductions in CLR/GFR of 20 and 28%, respectively (P<0.05).7. The results indicate that at clinically relevant concentrations the renal tubular secretion of ranitidine is inhibited by trimethoprim, but not by amantadine, pseudoephedrine or triamterene.
EFFECT OF cGMP INHIBITORS ON THE ACTIONS OF NITRODILATORS IN RAT AORTA
Authors: van der Zypp Andrea , Majewski Henryk 
Published: June 2007

SUMMARY1. The involvement of cGMP in vasodilatation produced by a range of nitrodilators was investigated using two different protein kinase G inhibitors, r(p) 8‐bromoguanosine‐3′5′‐cyclic monophosphothioate (RBrcGMPS) and KT5823.2. The nitric oxide donors sodium nitroprusside (SNP), glyceryltrinitrate (GTN) and s‐nitroso‐acetylpenicillamine (SNAP), the endothelium‐dependent vasodilator acetylcholine (ACh) as well as the cGMP analogues 8‐(4‐chlorophenylthio)‐cGMP (CPTcGMP) and β‐phenyl‐1‐N2‐etheno‐8‐bromo‐cGMP (PETcGMP) all relaxed rat aortic rings preconstricted with phenylephrine (0.1 μmol/L).3. The protein kinase G inhibitor KT 5823 (10 μmol/L) produced a very small inhibition of the vasodilatation produced by GTN, but had no effect against vasodilatation produced by SNP, CPTcGMP or PETcGMP, which suggests that KT 5823 is not a useful tool in this system.4. In contrast, RBrcGMPS (0.5 mmol/L) produced a rightward shift of the concentration‐response curves to SNP, CPTcGMP and PETcGMP. RBrcGMPS (0.5 mmol/L) also completely abolished vasodilatation to ACh and GTN but, surprisingly, had no effect on vasodilatation produced by SNAP.5. The guanylate cyclase inhibitor 1H‐[1,2,4] oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ; 1 and 10 μmol/L) completely inhibited the relaxation produced by GTN, whereas SNAP still had an appreciable relaxant effect after ODQ (1 μmol/L).6. The differential effect of RBrcGMPS and ODQ on the nitrodilators suggests that there are differences in the mechanism of dilatation between the nitrodilators.
CARDIOVASCULAR CONSEQUENCES OF OBESITY: ROLE OF LEPTIN
Authors: Haynes William G. , Morgan Donald A. , Walsh Susan A. , Sivitz William I. , Mark Allyn L. 
Published: June 2007

SUMMARY1. Several mechanisms have been implicated in the association between obesity and hypertension, including salt‐sensitivity, insulin resistance and sympathetic activation. Obese animals and humans exhibit exaggerated blood pressure responses to increases in salt intake.2. Although insulin resistance is common in obesity, it is clear that abnormal insulin action is not the sole or sufficient cause of hypertension in obesity. Obesity is associated with increased activity of the sympathetic nervous system. Sympathetic blockade has been reported to attenuate sodium retention and hypertension in experimental models of obesity.3. The mediators responsible for salt sensitivity, insulin resistance and sympathetic activation in obesity remain unclear.4. The novel protein hormone leptin is produced almost exclusively by adipose tissue and acts in the central nervous system through a specific receptor and multiple neuropeptide pathways to decrease appetite and increase energy expenditure.5. Increasing evidence suggests that leptin may have wider actions influencing autonomic, cardiovascular, renal and endocrine function. We have shown that leptin increases sympathetic nerve activity to kidney, hindlimb and adrenal gland, in addition to brown adipose tissue.6. Despite this sympathoexcitatory action, acute systemic administration of leptin does not acutely increase arterial pressure or heart rate in anaesthetized animals. This may reflect opposing antihypertensive actions of leptin. For example, leptin increases renal sodium and water excretion, apparently through a direct tubular action. In addition, leptin increases systemic insulin sensitivity, even in the absence of weight loss.7. In conclusion, leptin may act as a mediator linking body adiposity with changes in insulin action, sympathetic neural outflow and renal sodium excretion. Alterations in leptin generation or action may, in part, underlie the sympathetic, endocrine and renal consequences of obesity.
ROLE OF HEPATIC FATTY ACID:COENZYME A LIGASES IN THE METABOLISM OF XENOBIOTIC CARBOXYLIC ACIDS
Authors: Knights Kathleen M. 
Published: June 2007

SUMMARY1. Formation of acyl‐coenzymes (Co)A occurs as an obligatory step in the metabolism of a variety of endogenous substrates, including fatty acids. The reaction is catalysed by ATP‐dependent acid:CoA ligases (EC 6.2.1.1‐2.1.3; AMP forming), classified on the basis of their ability to conjugate saturated fatty acids of differing chain lengths, short (C2‐C4), medium (C4‐C12) and long (C10‐C22). The enzymes are located in various cell compartments (cytosol, smooth endoplasmic reticulum, mitochondria and peroxisomes) and exhibit wide tissue distribution, with highest activity associated with liver and adipose tissue.2. Formation of acyl‐CoA is not unique to endogenous substrates, but also occurs as an obligatory step in the metabolism of some xenobiotic carboxylic acids. The mitochondrial medium‐chain CoA ligase is principally associated with metabolism via amino acid conjugation and activates substrates such as benzoic and salicylic acids. Although amino acid conjugation was previously considered an a priori route of metabolism for xenobiotic‐CoA, it is now recognized that these highly reactive and potentially toxic intermediates function as alternative substrates in pathways of intermediary metabolism, particularly those associated with lipid biosyntheses.3. In addition to a role in fatty acid metabolism, the hepatic microsomal and peroxisomal long‐chain‐CoA‐ligases have been implicated in the formation of the acyl‐CoA thioesters of a variety of hypolipidaemic and peroxisome proliferating agents (e.g. cloflbric acid) and of the r(‐)‐enantiomers of the commonly used 2‐arylpropionic acid non‐steroidal anti‐inflammatory drugs (e.g. ibuprofen). In vitro kinetic studies using rat hepatic microsomes and peroxisomes have alluded to the possibility of xenobiotic‐CoA ligase multiplicity. Although cDNA encoding a long‐chain ligase have been isolated from rat and human liver, there is currently no molecular evidence of multiple isoforms. The gene has been localized to chromosome 4 and homology searches have revealed a significant similarity with enzymes of the luciferase family.4. Increasing recognition that formation of a CoA conjugate increases chemical reactivity of xenobiotic carboxylic acids has led to an awareness that the relative activity, substrate specificity and intracellular location of the xenobiotic‐CoA ligases may explain differences in toxicity.5. Continued characterization of the human xenobiotic‐CoA ligases in terms of substrate/inhibitor profiles and regulation, will allow a greater understanding of the role of these enzymes in the metabolism of carboxylic acids.
CYTOCHROME P450 KNOCKOUT MICE: NEW TOXICOLOGICAL MODELS
Authors: McKinnon Ross A. , Nebert Daniel W. 
Published: June 2007

SUMMARY1. Despite the frenetic pace of cytochrome P450 (CYP) research, important questions remain about the possible role of xenobiotic‐metabolizing CYP in development and cellular homeostasis.2. The recent experimental development of CYP null mouse lines has provided valuable new models for addressing these issues, as well as providing novel in vivo models to study the precise role of CYP in chemical‐mediated toxicity.3. The present review summarizes results from the three Cyp gene knockout mouse lines generated so far and looks at likely future directions of this research field.4. Also discussed are null mouse lines with targeted mutations in genes encoding receptors having primary roles in Cyp gene regulation.
ACUTE LITHIUM ADMINISTRATION IMPAIRS THE ACTION OF PARATHYROID HORMONE ON RAT RENAL CALCIUM, MAGNESIUM AND PHOSPHATE TRANSPORT*
Authors: Carney Shane , Jackson Peggy 
Published: June 2007

SUMMARY1. Chronic lithium (Li+) treatment commonly produces a state of hyperparathyroidism in humans and rat although the mechanism is unknown.2. The present study evaluated the acute effect of Li+ on renal electrolyte transport, particularly Ca2+ and Mg2+ in thyroparathyroidectomized (TPTX) and intact rats.3. The acute administration of Li+ significantly increased water, sodium, potassium and phosphate excretion in both TPTX and intact animals; however, Ca2+ and Mg2+ excretion was only increased in the intact group. Fractional excretion (FE) of Ca2+ and Mg2+ increased from 2.2±0.2 to 3.5±0.3% and 12±2 to 18±2%, respectively (P<0.01).4. In further experiments in TPTX rats, Li+ administration inhibited the usual reduction in urine Ca2+ and Mg2+ excretion following parathyroid hormone (PTH) administration and inhibited the phosphaturia. However, supramaximal concentrations of PTH overcame this inhibitory effect. For example, an FECa of 3.8±0.2% was reduced to 1.4±0.2% and 1.7±0.2% with maximal and supramaximal PTH concentrations, respectively, while in the presence of Li+ an FEca of 4.0±0.2 was decreased to 2.8±0.2 and then 1.9±0.3% with the same PTH concentrations.5. The inhibitory effect of Li+ was reduced with a lower plasma Li+ concentration (0.7±0.2 vs 1.6–1.8 mmol/L). The FEMg results were comparable.6. These results demonstrate that Li+ directly inhibits PTH‐mediated renal reabsorption of Ca2+ and Mg2+ and also blunts PTH‐mediated phosphaturia. Therefore, the hyperparathyroidism in humans following Li+ treatment may be a consequence of reduced renal Ca2+ reabsorption.
IS A HYPERTENSINOGENIC FACTOR PRESENT IN THE KIDNEY OF HYPERTENSIVE DAHL RATS?
Authors: Zhou Ming Sheng , Nishida Yasuhiro , Chen Qing Hui , Murakami Hiroshi , Hosomi Hiroshi , Kosaka Hiroaki 
Published: June 2007

SUMMARY1. Early studies suggest that hypertension in Dahl salt‐sensitive (S) rats is related to an uncommon humoral factor that may be released from the kidney.2. To investigate whether the kidney releases a hypertensino‐genic factor for developing salt‐induced hypertension in S rats, we examined a pressor effect, or vascular contractive activity of a kidney extract from S rats using a conscious recipient rat or an isolated aortic ring.3. Donor S and Dahl salt‐resistant (R) rats were fed a 0.4 or 8% NaCl diet for 4 weeks and were then used to provide four kinds of kidney extracts (S‐0.4%, S‐8%, R‐0.4%, R‐8%). The systolic arterial pressure (SAP) was significantly increased in donor S rats fed an 8% NaCl diet compared with other donor rat groups.4. All four types of kidney extract increased mean arterial pressure (MAP) in a recipient rat fed a 0.4% NaCl diet. However, the increase in MAP observed following infusion of the S‐8% extract was the least of all groups. An angiotensin AT1 receptor antagonist, CV‐11974, abolished any pressor effect of all kidney extracts. In an in vitro experiment, all four types of kidney extract evoked contractile responses in aortic rings, but elicited no significant difference in aortic ring contractile force.5. These results suggest that the kidney of S rats may not release an active hypertensinogenic factor that would cause salt‐induced hypertension.
MAGNOLOL DECREASES BODY TEMPERATURE BY REDUCING 5 HYDROXYTRYPTAMINE RELEASE IN THE RAT HYPOTHALAMUS
Authors: Hsieh MT , Chueh FY , Lin MT 
Published: June 2007

SUMMARY1. The effects of magnolol, isolated and purified from the cortex of Magnolia officinalis Rehd. et Wils, on thermoregulation and hypothalamic release of 5‐hydroxytryptamine (5‐HT) by in vivo microdialysis were assessed in normothermic rats and in febrile rats treated with interleukin‐1β.2. Intraperitoneal administration of magnolol (25–100 mg/kg) produced a decrease in colon temperature, an increase in foot skin temperature, a decrease in metabolic rate and a decrease in the endogenous release of 5‐HT in the rat hypothalamus.3. Depletion of rat brain 5‐HT, produced by intracerebro‐ventricular pretreatment with 5,7‐dihydroxytryptamine, attenuated the magnolol‐induced hypothermia, cutaneous vasodilation and decreased metabolism.4. Intracerebroventricular administration of (±)‐2,5‐dimethoxy‐4‐iodoamphetamine (a 5‐HT2 receptor agonist; 5–10 μg/5 μL) increased basal colon temperature and reversed the magnolol‐induced hypothermia.5. The increases in both colon temperature and hypothalamic 5‐HT release produced by interleukin‐1β injection were attenuated by treatment with magnolol.6. The data suggest that magnolol decreases body temperature (due to increased heat loss and decreased heat production) by reducing 5‐HT release in rat hypothalamus.
CHARACTERIZATION OF A MAJOR SLOW OSCILLATION IN THE MESENTERIC CIRCULATION OF CONSCIOUS RATS
Authors: Létienne Robert , Julien Claude , Zhang Zhi‐Qi , Barrès Christian 
Published: June 2007

SUMMARY1. Little is known about spontaneous slow rhythms in regional circulations. The present study was aimed at characterizing low‐frequency (LF; 78–269 mHz) oscillations in the mesenteric and hindquarter circulations of conscious rats.2. Mean arterial pressure (MAP) and indices (pulsed Doppler technique) of mesenteric (n= 25) and hindquarter (n= 23) blood flows were recorded in conscious, freely moving rats during 1 h periods. Fast Fourier transform analysis was applied to beat‐to‐beat data after resampling at 10 Hz of consecutive 205 s time series.3. A major oscillation centred at 164±4mHz was present in the mesenteric, but not in hindquarter, circulation. Consequently, LF power accounted for approximately 43% of the overall variability of mesenteric blood flow. Cross‐spectral analysis performed between MAP and mesenteric blood flow indicated that fractional changes in flow were approximately two‐fold of those in MAP, in pressure, at the peak frequency.4. Acute blockade of the autonomic, renin‐angiotensin and vasopressin systems combined with noradrenaline infusion (n= 7) reduced the frequency of the mesenteric blood flow oscillation (115 ± 6 mHz) but did not change its contribution to overall flow variability (approximately 48%). A clear oscillation was still present after acute inhibition of nitric oxide (NO) synthesis with NG‐nitro‐l‐arginine methyl ester (n= 8), but was virtually absent in chronically guanethidine‐sympathectomized rats (n= 12).5. In conclusion, the mesenteric blood flow of conscious rats exhibits a major slow oscillation that originates in the mesenteric vasculature and is not secondary to the activity of the major pressor systems or to the cyclic release of NO. Because of the strong attenuation of the oscillation in sympathectomized rats, we suggest that adrenergic vasoconstrictor tone plays a permissive role in its genesis.
SIGNAL TRANSDUCTION BY PROTEIN KINASE C IN MAMMALIAN CELLS
Authors: Kanashiro Celia A. , Khalil Raouf A. 
Published: June 2007

SUMMARY1. The past two decades have witnessed great advances in our understanding of the role of protein kinase C (PKC) in signal transduction. The Ca2+‐activated, phospholipid‐dependent protein kinase discovered by Nishizuka's group in 1977 is now a family of at least 11 isoforms. Protein kinase C isoforms exist in different proportions in a host of mammalian cells and each isoform has a characteristic subcellular distribution in each cell type.2. Stimulation of a specific PKC is oform often causes redistribution of the isoform from one subcellular compartment to another compartment where it complexes with and phosphorylates a specific protein substrate.3. The interaction of a specific PKC isoform with its protein substrate may directly activate a specific function of the cell or may trigger a cascade of protein kinases that ultimately stimulates a specific response in differentiated cells or regulates growth and proliferation in undifferentiated cells.
TRANSCARDIAC 5‐HYDROXYTRYPTAMINE RELEASE AND IMPAIRED CORONARY ENDOTHELIAL FUNCTION IN PATIENTS WITH VASOSPASTIC ANGINA
Authors: Murakami Yo , Shimada Toshio , Ishinaga Yuji , Kinoshita Yoshihisa , Kin Hakutetsu , Kitamura Jun , Ishibashi Yutaka , Murakami Rinji 
Published: June 2007

SUMMARY1. The present study was designed to test the hypotheses whether platelet degranulation across the coronary bed is detectable during non‐ischaemic periods in patients with vasospastic angina (VSA) and whether the exogenous nitric oxide (NO) donor nitroglycerin (GTN) is able to modify platelet degranulation, reflecting an impaired endothelial production of NO.2. We studied 13 patients with VSA and 10 controls. The time course of coronary sinus (CS) plasma 5‐hydroxytryptamine (5‐HT) levels was evaluated every 4 h before and after intravenous infusion of GTN over a period of 40 h. Coronary sinus plasma 5‐HT levels were significantly higher at any measured time point in patients with VSA compared with control and were significantly decreased in patients with VSA following treatment with GTN, but not in controls. Femoral artery plasma 5‐HT levels remained almost constant throughout the study. The ratio of CS:aorta 6‐keto‐prostaglandin F1α was significantly and inversely correlated with the transcardiac plasma 5‐HT difference only in patients with VSA (r=−0.68; P < 0.02; n= 13).3. The time course of CS 5‐HT levels confirmed significant platelet degranulation across the coronary bed supplied by the spasming artery in patients with VSA and this was modified by GTN. The present data suggest that platelet degranulation occurs during non‐ischaemic periods in patients with VSA and that prostacyclin biosynthesis may be a compensatory response to an impaired endothelial release of NO, limiting the degree of the effects of platelet degranulation.