bluuebunny/crossref_metadata_2025_split huggingface dataset:
AUTONOMIC BLOCKADE AMPLIFIES CORTISOL‐INDUCED HYPERTENSION IN MAN
Authors: Tam Sim Horn , Williamson Paula M. , Kelly John J. , Whitworth Judith A. 
Published: June 2007

SUMMARY1. We investigated the role of the autonomic nervous system (ANS) in Cortisol induced hypertension using the technique of total autonomic blockade (AB).2. Four healthy young males were given 50 mg Cortisol 6 hourly for 6 days. On the day prior to, and the last day of, Cortisol treatment, AB was produced using oral prazosin 1 mg, intravenous clonidine 300 μg, propranolol 0.2 mg/kg and atropine 2 mg. The adequacy of blockade was assessed using the haemodynamic response to Valsalva manoeuvre.3. Cortisol produced a significant rise in systolic blood pressure (130 ± 2 vs 110 ± 1 mmHg, pre vs post Cortisol; P<0.01). On the final treatment day, AB augmented the increase in diastolic blood pressure (ΔDBP), mean arterial pressure (ΔMAP) and heart rate (ΔHR) compared to the pre‐treatment day, ΔDBP: 43 ± 6 vs 17 ± 4 mmHg, post vs pre Cortisol, P<0.005, ΔMAP: 39 ± 4 vs 14 ± 4 mmHg, P<0.001, ΔHR: 45 ± 5 vs 26 ± 4 b.p.m., P<0.05. The change in systolic blood pressure (ΔSBP) was not statistically significant (32 ± 4 vs7 ± 3 mmHg, P= 0.065).4. These results suggest that the ANS exerts a modulating influence on the hypertensive effect of Cortisol.
INTERACTION OF EXOGENOUS OUABAIN AND CHRONIC MINERALOCORTICOID TREATMENT IN THE KIDNEY OF THE CONSCIOUS SHEEP
Authors: Yates NA , McDougall JG 
Published: June 2007

SUMMARY1. Ouabain is known to have natriuretic effects only at high doses, and therefore if endogenously produced ouabain has a role in the regulation of sodium excretion, the renal response to ouabain must be increased substantially in certain physiological situations. The aim of this study is to determine whether treatment with the mineralocorticoid, aldosterone, potentiates that natriuretic response to ouabain.2. Six conscious sheep received renal arterial infusion of either vehicle or aldosterone (3 μg/h). Forty hours after commencement of infusion ouabain was infused into the renal artery at 400 μg/h for 60min. A second infusion of ouabain was administered on the 6th day of aldosterone treatment.3. In the absence of aldosterone, the effects on sodium excretion produced by ouabain infusion at 400 μg/h into the renal artery were variable and not statistically significant. Ouabain infusion after 40 h of aldosterone treatment increased sodium excretion from 40 ± 14 to 676 ± 69 μmol/min in the second hour following cessation of ouabain infusion (P< 0.001). Ouabain infusion after 6 days of aldosterone treatment increased sodium excretion similarly. Ouabain‐stimulated sodium excretion was significantly greater during aldosterone treatment compared to vehicle treatment (P<0.05). In contrast, no enhancement of effect was observed after acute treatment with aldosterone.4. These results demonstrate potentiation of the natriuretic response to ouabain infusion by chronic mineralocorticoid treatment and suggest a potential role of endogenous digitalislike factor in the physiological control of sodium homeo stasisaldo sterone, endogenous digitalis‐like factor, ouabain, sodium excretion.
LONG‐TERM INCREASES IN RENAL SYMPATHETIC NERVE ACTIVITY AND HYPERTENSION
Authors: Osborn Jeffrey L. , Plato Craig F. , Gordin Erez , He Xiao Rui 
Published: June 2007

SUMMARY1. Essential hypertensive patients have been characterized by increased sympathetic nerve activity, increased peripheral vascular tone, decreased plasma volume and normal cardiac output when compared with normotensive subjects. Bilateral renal denervation reduces the magnitude or delays the onset of the blood pressure response in numerous models of experimental hypertension regardless of the aetiology of the elevation in arterial pressure.2. Using a servocontrolled intrarenal infusion system, we have elevated intrarenal noradrenaline concentration via intermittent renal artery infusion without decreasing renal blood flow as a method of simulating selective elevation of renal sympathetic outflow.3. Chronic intrarenal adrenergic stimulation increased arterial pressure within 24 h and this hypertension persisted for 28 consecutive days. The elevated arterial pressure was not associated with sustained increases in plasma renin activity, aldosterone, circulating catecholamines, arginine vasopressin or significant renal vasoconstriction. Urinary sodium excretion was chronically elevated and the dogs remained in negative sodium balance for the duration of the intrarenal noradrenaline infusion.4. After 2 weeks of elevated intrarenal neurotransmitter coupled with hypertension, renal vascular reactivity to further adrenergic stimulation was significantly increased because the hypertension was maintained during continual reductions in the daily dosage of neurotransmitter allowed to be infused by the servocontroller. After only 28 days of noradrenaline infusion, renal vascular hypertrophy developed in vessels from 150–300 μm.5. We conclude that selective and intermittent increases in intrarenal adrenergic neurotransmitter are sufficient to elicit chronic hypertension in the absence of volume expansion. This intrarenal neuroadrenergic hypertension is closely associated with the haemodynamic parameters which characterize a major subset of human essential hypertensives.
INTERACTIONS BETWEEN ANGIOTENSIN II AND THE SYMPATHETIC NERVOUS SYSTEM IN THE THE LONG‐TERM CONTROL OF ARTERIAL PRESSURE
Authors: Brooks Virginia L. 
Published: June 2007

SUMMARY1. The role of the renin‐angiotensin system in long‐term control of sympathetic activity and arterial pressure is reviewed.2. There is evidence that favours a necessary role for the sympathetic nervous system in long‐term arterial pressure regulation. First, appropriate changes in sympathetic activity appear to be produced in response to chronic changes in blood volume or blood pressure. Second, prevention of the normal homeostatic decrease in sympathetic activity in response to an increase in sodium intake produces hypertension.3. Long‐term changes in sympathetic activity cannot be mediated by the baroreceptor reflex, because it adapts to sustained changes in pressure. Therefore, an hypothesis is presented that evokes a key role for angiotensin II (AngII) in determining the chronic level of sympathetic activity. The key feature of this model is that the role of AngII is non‐adaptive: chronic changes in extracellular fluid volume produce sustained reciprocal changes in AngII, and long‐term increases in AngII produce sustained increases in sympathetic activity.4. Evidence is reviewed that suggests that a lack of the normal suppression in AngII and/or sympathetic activity in response to an increase in sodium intake produces salt‐sensitive hypertension.
STEREOCHEMISTRY IN ANAESTHESIA
Authors: Sidebotham David A. , Schug Stephan A. 
Published: June 2007

SUMMARY1. Interest in the pharmacokinetic and pharmacodynamic properties of the enantiomers of chiral drugs has greatly increased in recent years. This is particularly so for agents used in anaesthesia.2. Chiral compounds are those that can exist in two non‐superimposable forms. Each form is termed an enantiomer or stereoisomer. Two naming systems are in use: one uses the terms (+) and (–) to indicate the direction the compound will rotate polarized light, while the other system, based on the absolute three‐dimensional structure of the enantiomers, uses the terms R and S.3. Investigation of the stereoisomers of the volatile anaesthetic agent isoflurane is increasing our understanding of the mechanism of general anaesthesia. Current evidence suggests a protein, rather than a lipid, receptor site.4. Investigation of the stereoisomers of local anaesthetics is increasing the safety of these drugs.5. For bupivacaine, a widely used amide local anaesthetic, important enantiomeric differences can be found for toxicity, clinical effect and pharmacokinetics. In particular S‐(–)‐bupivacaine has an improved central nervous system and cardiac safety profile. This is partly explained by the pharmacokinetic differences.6. Based on these differences, ropivacaine, a propyl homo‐logue of bupivacaine, has been produced solely as the S‐(–)‐enantiomer. The available evidence suggests significantly improved safety for this agent over racemic bupivacaine.
RELAXANT EFFECTS OF VASODILATOR PEPTIDES ON ISOLATED BASILAR ARTERIES FROM STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Nishimura Yoshitaka , Suzuki Aritomo 
Published: June 2007

SUMMARY1. The relaxant effects of vasodilator peptides were examined in ring preparations of basilar arteries from stroke‐prone spontaneously hypertensive rats (SHRSP) and Wistar‐Kyoto (WKY) rats.2. Vasoactive intestinal peptide and peptide histidine iso‐leucine produced similar endothelium‐independent relaxations in basilar arteries from WKY rats and SHRSP. Calcitonin gene‐related peptide (CGRP) elicited endothelium‐independent relaxations in both groups and the CGRP‐induced relaxation was greater in SHRSP than in WKY rats. Substance P and neurokinin A did not relax basilar arteries from either group.3. Both WKY rat and SHRSP basilar arteries were relatively insensitive to atrial natriuretic peptide, brain natriuretic peptide and C‐type natriuretic peptide.4. Bradykinin (BK) potently relaxed basilar arteries with endothelium, but BK produced contractions in endotheliumrubbed arteries in both WKY rats and in SHRSP. There was no significant difference in the relaxant response to BK between WKY rat and SHRSP arteries.5. Adrenomedullin (AM) produced endothelium‐independent relaxations in both groups and the relaxant response to AM was significantly greater in SHRSP than in WKY rats.6. Human CGRP(8–37; 1 μmol/L), a CGRP receptor antagonist, significantly inhibited both relaxant responses induced by CGRP and AM in WKY rats and in SHRSP arteries.7. Among various peptides tested, the responses to CGRP and AM were higher in basilar arteries from SHRSP than in those from WKY rats. The relaxation produced by AM may be via CGRP receptors in WKY rat and SHRSP basilar arteries.
INFLUENCE OF AGEING ON CILIARY BEAT FREQUENCY AND ON CILIARY RESPONSE TO LEUKOTRIENE D4 IN GUINEA‐PIG TRACHEAL EPITHELIUM
Authors: Joki Susanna , Saano Veijo 
Published: June 2007

SUMMARY1. In the present study on guinea‐pig tracheal epithelium, the influence of age on ciliary beat frequency (CBF) was investigated.2. An age‐dependent decrease in CBF was seen: as the age of the guinea‐pig increased from 0.9 to 16.3 months, CBF decreased from 20.2 to 6.9 Hz.3. The effect of leukotriene D4 (LTD4) on CBF was also examined using tracheal explants from guinea‐pigs of varying ages. The lower CBF of the older animal was increased by LTD4 to a larger extent than was the higher CBF seen in explants taken from younger animals.4. Ciliary activity and possibly also the sensitivity of the cilia to drugs, seems to be dependent upon the age of the animal, which has to be taken into consideration when comparing the results of different studies on the effects of xenobiotics on mucociliary function.
EFFECTS OF BKCa CHANNELS ON THE REDUCTION OF CYTOSOLIC Ca2+ IN cGMP‐INDUCED RELAXATION OF GUINEAPIG TRACHEA
Authors: Mikawa Kenichiro , Kume Hiroaki , Takagi Kenzo 
Published: June 2007

SUMMARY1. In order to examine the mechanisms of cGMP‐induced relaxation in airway smooth muscle, the effects of atrial natriuretic peptide (ANP) and 8‐brom cGMP on muscle tone were studied by measuring isometric tension, while the effects on cytosolic Ca2+ concentrations were studied by measuring the spectra of fura‐2 loaded in guinea‐pig tracheal strips.2. Atrial natriuretic peptide and 8‐brom cGMP caused a concentration‐dependent inhibition of spontaneous tone in the guinea‐pig trachea. The relaxant effects of these agents on spontaneous tone were markedly suppressed in the presence of iberiotoxin (IbTX), a selective inhibitor of large‐conductance Ca2+‐activated K+ (BKca) channels. Iberiotoxin (30 nmol/L) markedly affected the maximal effect induced by ANP and 8‐brom cGMP and augmented EC70 values for ANP and EC50values for 8‐brom cGMP approximately 27‐ and 17‐fold, respectively. The inhibitory effects of IbTX on relaxation induced by these agents were diminished in the presence of 1 μmol/L nifedipine, an antagonist of voltage‐operated Ca2+channels (VOCC).3. The inhibitory action of ANP and 8‐brom cGMP on spontaneous tone was not affected by the presence of 10 μmol/L glibenclamide, an inhibitor of ATP‐sensitive K+ channels, and 100 nmol/L apamin, an inhibitor of small‐conductance Ca2+‐activated K+ channels. When these agents were applied to tissues precontracted by high (40mmol/L) K+, the relaxant effects of these agents markedly diminished.4. The extracellular Ca2+‐dependent contraction was inhibited in the presence of 0.3 μmoI/L ANP or 0.1 mmol/L 8‐brom cGMP. Concentration—response curves to extracellular Ca2+ (0.03—2.4 mmol/L) were markedly diminished by exposure to these agents. The maximal effect induced by extracellular Ca2+ was affected by these agents.5. Atrial natriuretic peptide caused an inhibition of spontaneous tone accompanied by a reduction in the intracellular Ca2+ concentration. In the presence of IbTX, the elimination of both muscle tone and cytosolic Ca2+ by ANP was suppressed.6. We conclude that ANP and 8‐brom cGMP activate BKca channels and that the inhibition of Ca2+ influx through VOCC, mediated by BKca channel activation, may be involved in cGMP‐dependent bronchodilation.
SPECIAL ARTICLE COMPARING METHODS OF MEASUREMENT
Authors: Ludbrook John 
Published: June 2007

SUMMARY1. The purpose of comparing two methods of measurement of a continuous biological variable is to uncover systematic differences not to point to similarities.2. There are two potential sources of systematic disagreement between methods of measurement: fixed and proportional bias.3. Fixed bias means that one method gives values that are higher (or lower) than those from the other by a constant amount. Proportional bias means that one method gives values that are higher (or lower) than those from the other by an amount that is proportional to the level of the measured variable.4. It must be assumed that measurements made by either method are attended by random error: in making measurements and from biological variation.5. Investigators often use the Pearson product—moment correlation coefficient (r) to compare methods of measurement. This cannot detect systematic biases, only random error.6. Investigators sometimes use least squares (Model I) regression analysis to calibrate one method of measurement against another. In this technique, the sum of the squares of the vertical deviations of y values from the line is minimized. This approach is invalid, because both y and x values are attended by random error.7. Model II regression analysis caters for cases in which random error is attached to both dependent and independent variables. Comparing methods of measurement is just such a case.8. Least products regression is the reviewer's preferred technique for analysing the Model II case. In this, the sum of the products of the vertical and horizontal deviations of the x,y values from the line is minimized.9. Least products regression analysis is suitable for calibrating one method against another. It is also a sensitive technique for detecting and distinguishing fixed and proportional bias between methods.10. An alternative approach is to examine the differences between methods in order to detect bias. This has been recommended to clinical scientists and has been adopted by many.11. It is the reviewer's opinion that the least products regression technique is to be preferred to that of examining differences, because the former distinguishes between fixed and proportional bias, whereas the latter does not.
SHORT COMMUNICATION EFFECTS OF α2‐ADRENOCEPTOR ANTAGONISTS AND IMIDAZOLINE2‐RECEPTOR LIGANDS ON NEURONAL DAMAGE IN GLOBAL ISCHAEMIA IN THE RAT
Authors: Craven John A. , Conway Elizabeth L. 
Published: June 2007

SUMMARY1. In the present study the neuroprotective effects of 3 mg/kg idazoxan, an α2‐adrenoceptor antagonist and imidazolinea‐receptor (I2‐receptor) ligand, 3 mg/kg methoxyidazoxan, a specific α2‐adrenoceptor antagonist, and 0.6 and 3 mg/kg BU224, a selective I2‐receptor ligand, were evaluated following 10 min of global ischaemia in rats.2. Neuronal cell counts in the CA1 region of the hippocampus 8 days postischaemia indicated 46–96% cell loss compared with control (P<0.001) and a 320% increase in [3H]‐PK11195 binding (P<0.001) used as a marker of gliosis. No significant neuroprotective effect could be detected on these markers of neuronal damage in the active treatment groups. In a subset of idazoxan‐treated rats, neuronal loss and gliosis was minimal.3. Mean body temperature over 3 h postischaemia was lower in idazoxan‐treated rats than in the other treatment groups (P< 0.001) and there was a correlation between mean body temperature and cell counts (P<0.01) and mean body temperature and gliosis in this group (P—0.057).4. These results indicate that at the doses used neither BU224 nor methoxyidazoxan are neuroprotective in this ischaemia model and they raise the possibility that any neuroprotective effect of idazoxan may be related to hypothermic effects of the drug.
MEDIATORS ON HUMAN AIRWAY SMOOTH MUSCLE
Authors: Armour Carol , Johnson Peter , Anticevich Sinthia , Ammit Alaina , McKay Karen , Hughes Margaret , Black Judith 
Published: June 2007

SUMMARY1. Bronchial hyperresponsiveness in asthma may be due to several abnormalities, but must include alterations in the airway smooth muscle responsiveness and/or volume.2. Increased responsiveness of airway smooth muscle in vitro can be induced by certain inflammatory cell products and by induction of sensitization (atopy).3. Increased airway smooth muscle growth can also be induced by inflammatory cell products and atopic serum.4. Mast cell numbers are increased in the airways of asthmatics and, in our studies, in airway smooth muscle that is sensitized and hyperresponsive.5. We propose that there is a relationship between mast cells and airway smooth muscle cells which, once an allergic process has been initiated, results in the development of critical features in the lungs in asthma.
INHIBITION OF ENDOTHELIAL CELL ADHESION MOLECULE EXPRESSION BY HIGH DENSITY LIPOPROTEINS
Authors: Barter PJ 
Published: June 2007

SUMMARY1. A low level of high density lipoprotein (HDL) cholesterol is highly predictive of premature coronary heart disease (CHD). It is unclear from human studies whether this relationship reflects an ability of HDL to protect against coronary disease or whether a low HDL in coronary patients is simply an epi‐phenomenon.2. Recent studies of transgenic mice provide strong evidence that HDL are directly anti‐atherogenic, although the mechanism of the protection is unknown. It is uncertain whether it relates to the involvement of HDL in plasma cholesterol transport or to a range of non‐lipid transport functions of HDL.3. We have recently reported HDL have the ability to inhibit the cytokine‐induced expression of adhesion molecules by endothelial cells, a process well recognized as an early event in the development of atherosclerosis.
ROLE OF NITRIC OXIDE IN THE CONTROL OF GLOMERULAR MICROCIRCULATINO
Authors: Ito Sadayoshi , Carretero Oscar A. , Abe Keishi 
Published: June 2007

SUMMARY1. Nitric oxide (NO) plays an important role in the control of glomerular haemodynamics and is synthesized from the amino acid L‐arginine by a family of enzymes, NO synthase (NOS).2. Nitric oxide synthase is present in the endothelium and also in the macula densa, a plaque of specialized tubular epithelial cells. Endothelial NOS is known to be stimulated by shear stress and hormones, while the factor that regulates the activity of macula densa NOS remains undefined.3. Studies with the in vitro microperfusion of glomerular arterioles have shown that the constriction of afferent arterioles (Af‐Art) induced by myogenic responses and angiotensin II (AngII) is stronger in the absence rather than in the presence of luminal flow. Furthermore, endothelial disruption or NOS inhibition abolishes such differences, suggesting that flow through the lumen stimulates the endothelium to synthesize and release NO, which in turn attenuates both the myogenic response and the action of AngII in the Af‐Art.4. In contrast, NOS inhibitors have no effect on efferent arteriolar (Ef‐Art) constriction induced by AngII.5. In preparations in which Af‐Art and the macula densa are simultaneously microperfused, selective inhibition of macula densa NOS has been shown to augment Af‐Art constriction when the NaCl concentration at the macula densa is high, suggesting that the macula densa produces NO, which in turn modulates tubuloglomerular feedback.6. Thus, the differential actions of NO in the Af‐Art, Ef‐Art and the macula densa may be important in the control of glomerular haemodynamics under various physiological and pathological conditions.
INTRARENAL LOCALIZATION OF NITRIC OXIDE SYNTHASE ISOFORMS AND SOLUBLE GUANYLYL CYCLASE
Authors: Star Robert A. 
Published: June 2007

SUMMARY1. Nitric oxide (NO) plays an important role in the regulation of renal function. To date, five isoforms of NO synthase (NOS) and four subunits of soluble guanylyl cyclase have been cloned. The kidney contains four isoforms of NOS and all sub‐units of soluble guanylyl cyclase.2. This review focuses on the intrarenal location of the isoforms of NOS and the subunits of soluble guanylyl cyclase.
COMPETITION BY SECOND MESSENGER SYSTEMS FOR RECEPTOR INTERACTION AND ACTIVATION: IMPLICATIONS FOR TISSUE‐SPECIFIC RESPONSES AND DISEASE THERAPY
Authors: Crouch Michael F. , Frew Ian J. , Simson Ljubov , Davy Deborah A. 
Published: June 2007

SUMMARY1. At any one instant, most receptors are now recognized to be able to stimulate multiple signal transduction pathways in a cell when activated by an appropriate hormone. These different signalling pathways appear to allow for distinct cellular responses, such as cell proliferation, differentiation, and shape change.2. In addition, many different types of cell will possess the same type of receptor. Therefore, for a hormone to be able to transmit differential signals to the various cell types able to respond to it, cells must discriminate the stimulus at some point. Such discrimination would seem to be an absolute requirement to allow a tissue‐specific response to an identical initial stimulus. In theory, this specificity could occur at many points in the receptor signal transduction cascade, including cytosolic receptor coupling systems and tissue/cell‐specific responsive genes.3. The present paper summarizes our work and that of others which has determined some of the coupling systems of G‐protein‐coupled receptors and tyrosine kinase receptors and how these systems may be interacting.4. In addition to these theoretical considerations, a potential therapeutic strategy underlies the ability of receptors to couple to more than one signal transduction system. If a response to a hormone were, for example, either cell proliferation or cell morphological change or differentiation and separate receptor‐coupled signalling systems were responsible for these effects, pharmacological intervention may allow the transfer from one signalling system to another. If such a change allowed a permanent change to the differentiated phenotype, this could potentially form the basis of a signal‐based cancer therapy.