bluuebunny/crossref_metadata_2025_split huggingface dataset:
ROLE OF NITRIC OXIDE AND TPEN, A POTENT METAL CHELATOR, IN ISCHAEMIC AND REPERFUSED RAT ISOLATED HEARTS
Authors: Ferdinandy Peter , Appelbaum Yori , Csonka Csaba , Blasig Ingolf E. , Tosaki Arpad 
Published: June 2007

SUMMARY1. The role of nitric oxide (NO) was studied in the control of ischaemic/reperfused cardiac function and the effect of N, N, N', N'‐tetrakis‐[2‐pyridylmethyl]‐ethylenediamine(TPEN), a potent metal chelator, on the regulation of cardiac NO formation.2. Rat isolated working hearts were subjected to 30 min is‐chaemia and reperfusion. The incidence of reperfusion‐induced ventricular fibrillation (VF), ventricular tachycardia (VT) and the recovery of cardiac function were measured. Nitric oxide was detected by electron spin resonance (ESR) spectroscopy.3. With 5.0, 7.5 and 10.0 μmol/L of TPEN administered prior to ischaemia, the drug produced a reduction in the incidence of VF from its control value of 100% to 25% (P<0.05), 17% (P<0.05) and 8% (P<0.05), respectively. The incidence of VT followed the same pattern.4. When TPEN was given at the moment of reperfusion, a reduction in the incidence of VF and VT was still observed. Reduction in the incidence of VF and VT was reflected in the improvement of cardiac function both in the pre‐ and post‐ischaemic TPEN‐treated groups.5. TPEN reduced basal cardiac NO content and prevented the accumulation of NO during ischaemia/reperfusion.6. The results show that TPEN exerts beneficial effects on postischaemic cardiac function and dysrhythmias in relation to inhibition of the accumulation of NO in ischaemic/reperfused myocardium.
ACETYLCHOLINE‐INDUCED SYSTEMIC VASODILATION RESISTANT TO NG‐NITRO‐L‐ARGININE IN ANAESTHETIZED RATS
Authors: Kakizoe Eiichi , Wang Dan‐Qiao , Kobayashi Yuta , Shimoura Keiko , Okunishi Hideki 
Published: June 2007

SUMMARY1. The effects of NG‐nitro‐L‐arginine (l‐NNA; 20mg/kg bodyweight (BW), i.v.) and metyrapone (300 mg/kg BW, s.c.) on acetylcholine (ACh)‐induced depressor responses were investigated in anaesthetized rats.2. Acetylcholine (0.05,0.5,5 μg/kg BW, i.v.) dose‐dependently evoked a sharp fall in mean blood pressure (BP) followed by a slow recovery under control conditions.3. Basal BP level was elevated when rats were treated with l‐NNA, indicating endogenous nitric oxide (NO) participated in BP regulation. However, pretreatment with l‐NNA did not attenuate but rather augmented the ACh‐induced maximum vasodilation. In contrast, the time for recovery of mean BP to the pre‐ACh administration level was shortened by l‐NNA. These observations suggested that ACh‐induced vasodilation consisted of two phases: a sharp and transient fall (phase 1) that was resistant to l ‐NNA followed by a longer depressor response (phase 2) that was suppressed by l‐NNA.4. To examine whether augmentation of phase 1 by l‐NNA resulted from the elevation of basal BP, an appropriate dose of phenylephrine was infused to obtain similar BP elevation. Phenylephrine infusion augmented the phase 1 in a similar manner to l‐NNA pretreatment but showed little effect on phase 2, supporting the selective inhibition of phase 2 by l‐NNA.5. The s.c. pretreatment with metyrapone for 3 days failed to attenuate phase 1. Thus, the involvement of endothelium‐derived hyperpolarizing factor that could be formed by a metyrapone‐sensitive oxidase in phase 1 was unlikely.6. These results suggest that some factor(s), which is not inhibitable by l‐NNA or metyrapone, may induce the phase 1 depressor response to ACh while NO is responsible for the phase 2 response. The mechanism inducing the phase 1 response remains to be identified.
PRECONDITIONING IMPROVES MYOCARDIAL FUNCTION AND REFLOW, BUT NOT VASODILATOR REACTIVITY, AFTER ISCHAEMIA AND REPERFUSION IN ANAESTHETIZED DOGS
Authors: Loke Kit E. , Woodman Owen L. 
Published: June 2007

SUMMARY1. The present study examines whether three cycles of brief coronary artery occlusion and reperfusion (i.e. ischaemic preconditioning; PC) can prevent vasodilator dysfunction and the impairment of myocardial reflow caused by prolonged ischaemia. Coronary blood flow, left ventricular dP/dt, systemic arterial blood pressure and heart rate were measured in open‐chest anaesthetized dogs.2. Sixty minute occlusion of the left circumflex coronary artery (LCx) and 60 min LCx reperfusion (ISC/REP; group 1) significantly reduced resting coronary blood flow (CBF, initial 29±3mL/min; ISC/REP 20±3mL/min, P<0.05 vx initial) and increased coronary vascular resistance (CVR, initial 4.1±0.6 mmHg/min per mL; ISC/REP 5.8±1.0 mmHg/min per mL, P<0.05 vs initial). By contrast CBF and CVR were not affected in dogs subjected to preconditioning before ischaemia (group 2: CBF, initial 24±4mL/min; PC+ISC/REP 23±4mL/min; CVR, initial 4.7±0.6 mmHg/min per mL; PC+ ISC/REP 5.3±1.0 mmHg/min per mL). These data suggest that ischaemic preconditioning prevents the ischaemia‐induced impairment of myocardial reflow.3. Ischaemia and reperfusion impaired coronary dilator responses to the endothelium‐dependent dilator acetylcholine (ACBF, after ISC/REP: 50±6% of initial) and the endothelium‐independent dilator glyceryl trinitrate (ΔCBF, ISC/REP: 46±6% of initial). Despite the improvement in reperfusion in the preconditioned group, there was no significant improvement in responses to acetylcholine (PC+ISC/REP 52±6% of initial) or glyceryl trinitrate (PC+ISC/REP 59±6% of initial) after ischaemia and reperfusion.4. The reduction in left ventricular dP/dt after ischaemia and reperfusion was significantly smaller in the preconditioned group indicating a lower level of impairment of cardiac contractility. In addition, we confirmed that preconditioning caused a significant reduction in infarct size and a reduction in the release of lactate dehydrogenase indicating less cardiac injury.5. These results suggest that although ischaemic preconditioning was able to improve both myocardial reperfusion and contractility, it was not able to preserve vasodilator function. Such a reduction in vasodilator reserve could prevent adequate myocardial perfusion under conditions of elevated oxygen demand.
EFFECTS OF AMLODIPINE AND NIFEDIPINE RETARD ON AUTONOMIC NERVE ACTIVITY IN HYPERTENSIVE PATIENTS
Authors: Minami Junichi , Ishimitsu Toshihiko , Kawano Yuhei , Matsuoka Hiroaki 
Published: June 2007

SUMMARY1. The effects of 1,4‐dihydropyridine calcium antagonists with different biological half‐lives, amlodipine and nifedipine retard on 24 h blood pressure (BP), heart rate (HR) and autonomic nerve activity in patients with essential hypertension were compared.2. Twenty patients (six men and 14 women; mean (±SEM) age 63±2 years) with essential hypertension were enrolled in the present study. Their ambulatory BP and electrocardiograms were monitored for 24 h at intervals of 30 min with a portable recorder after a 4 week drug‐free period, after a 4 week treatment period with amlodipine (2.5 or 5 mg once daily) and after a 4 week treatment period with nifedipine retard (10 or 20 mg twice daily). The order of the three periods was randomized. Autonomic nerve activity was evaluated by power spectral analysis of HR variability, using the high frequency (HF) component as an index of parasympathetic activity and the ratio of the low frequency (LF) to the HF component as an index of sympathovagal balance.3. Amlodipine and nifedipine retard significantly lowered the 24 h BP to a similar extent (amlodipine: −12.7±2.6/−5.6±1.4mmHg, P<0.01/P<0.01; nifedipine retard: −15.1±2.1/−6.9+1.5 mmHg, P<0.01/<P0.01). Amlodipine did not change the 24 h average HR, while nifedipine retard significantly increased it (+3.3±1.2 b.p.m., P<0.05). Amlodipine also did not change the HF component or the ratio of the LF to the HF component. However, nifedipine retard significantly decreased the HF component (P<0.01) and increased the ratio of the LF to the HF component (P<0.05).4. These results suggest that nifedipine retard caused a decrease in parasympathetic activity and an increase in sympathetic activity with reflex tachycardia in these patients with essential hypertension, while amlodipine did not produce such effects on the autonomic nervous system.
INHIBITORY EFFECT OF ALDOSTERONE ON THE NATRIURETIC RESPONSE TO ATRIAL NATRIURETIC PEPTIDE IN HYPOCAPNIC RATS
Authors: Kanauchi Hajime , Mimura Yoshikazu 
Published: June 2007

SUMMARY1. Previous studies have shown that acute hypocapnia blunts the natriuretic effect of atrial natriuretic peptide (ANP) independently of the renal nerves and that the effect of ANP is restored by total adrenalectomy. We investigated the natriuretic response to ANP in potassium canrenoate (aldosterone receptor antagonist)‐treated rats to clarify whether aldosterone contributes to the attenuated natriuretic response to ANP during hypocapnia.2. Wistar rats, challenged with either canrenoate or saline vehicle, were infused with 10 μg/kg per h ANP during acute hypocapnia achieved by mechanical ventilation.3. In saline‐treated hypocapnic rats, ANP infusion failed to increase the fractional excretion of sodium (FENa) (from 3.49± 0.26 to 5.03±0.42%, respectively; n= 6) which was similar to values for time control rats (from 3.00±0.61 to 4.41±0.68%; n= 6). The hyporesponsiveness to ANP during hypocapnia was also evident when the FENa was compared with that of normocapnic rats (from 3.92±0.69 to 7.87±0.45%; P < 0.05; n= 6). In canrenoate‐treated rats, ANP infusion caused greater increases in sodium excretion (FENA from 3.05±0.71 to 7.21±0.45%; P < 0.05; n= 8) than saline infusion (FENa from 4.16± 1.11 to 5.47±0.66%; n= 6), despite the hypocapnia. The increase in FENa after ANP infusion during hypocapnia (4.16±0.86%) was similar to the increase seen during normocapnia (3.89±0.86%; n= 9).4. In conclusion: (i) acute hypocapnia blunts the natriuretic effects of ANP; and (ii) this attenuation is restored by potassium canrenoate treatment. The data suggest that aldosterone plays an important role by limiting the renal actions of ANP during acute hypocapnia.
INHIBITION OF CARDIAC BAROREFLEX SENSITIVITY AFTER CENTRAL DOPAMINERGIC STIMULATION
Authors: van den Buuse Maarten , Wilks David P. , Cornish Jennifer L. 
Published: June 2007

SUMMARY1. Stimulation of the mesolimbic dopamine system, by microinjection of the substance P analogue [pGlu5, MePhe8, Sar9]sub‐stance P (DiMe‐C7) into the ventral tegmental area induced a prolonged increase in blood pressure and circulating levels of vasopressin.2. In the present study, this treatment produced a significant decrease of cardiac baroreflex sensitivity in conscious rats. After pretreatment with the dopamine receptor antagonist raclopride, central stimulation failed to produce any changes in baroreflex parameters.3. The central dopamine‐mediated decrease in baroreflex sensitivity may be involved in functionally potentiating the circulatory actions of vasopressin.
A LINKAGE AND CROSS‐SECTIONAL STUDY OF HYPERTENSION AND OBESITY USING A POLY(A) Alu‐REPEAT POLYMORPHISM AT THE GLUCAGON RECEPTOR GENE LOCUS (17q25)
Authors: Rutherford S. , Boatwright SD , Samwell GA , Morris BJ , Griffiths LR 
Published: June 2007

SUMMARY1. Previous glucagon receptor gene (GCGR) studies have shown a Gly40Ser mutation to be more prevalent in essential hypertension and to affect glucagon binding affinity to its receptor. An Alu‐repeat poly(A) polymorphism colocalized to GCGR was used in the present study to test for association and linkage in hypertension as well as association in obesity development.2. Using a cross‐sectional approach, 85 hypertensives and 95 normotensives were genotyped using polymerase chain reaction primers flanking the Alu ‐repeat. Both hypertensive and normotensive populations were subdivided into lean and obese categories based on body mass index (BMI) to determine involvement of this variant in obesity. For the linkage study, 89 Australian Caucasian hypertension affected sibships (174 sib‐pairs) were genotyped and the results were analysed using genehunter, Mapmaker Sibs, erpa and splink (all freely available from http://linkage.rockefeller.eduVsoft/list.html).3. Cross‐sectional results for both hypertension and obesity were analysed using Chi‐squared and Monte Carlo analyses. Results did not show an association of this variant with either hypertension (X2= 6.9, P= 0.14; Monte Carlo X2= 7.0, P= 0.11; n= 5000) or obesity (X2= 3.3, P= 0.35; Monte Carlo X2= 3.26, P= 0.34; n= 5000). In addition, results from the linkage study using hypertensive sib‐pairs did not indicate linkage of the poly(A) repeat with hypertension. Hence, results did not indicate a role for the Alu‐repeat in either hypertension or obesity. However, as the heterozygosity of this poly(A) repeat is low (35%), a larger number of hypertensive sib‐pairs may be required to draw definitive conclusions.
EFFECTS OF LONG‐TERM EXTRARENAL ANGIOTENSIN II INFUSION ON RENAL VASCULAR RESPONSIVENESS TO VASOACTIVE AGENTS
Authors: Fitzgerald Sharyn M. , Stevenson Kathleen M. , Evans Roger G. , Anderson Warwick P. 
Published: June 2007

SUMMARY1. We tested whether chronic intrarenal angiotensin II (AngH) infusion altered renal vascular responsiveness to vasoactive agents, which would provide evidence of vascular structural changes.2. The renal blood flow (RBF) responses to renal arterial administration of bolus doses of acetylcholine, glyceryl trinitrate, AngH and noradrenaline were measured before commencement of and 1 day after cessation of 28 days intrarenal Angll infusion (0.5 ng/kg per min) in chronically instrumented conscious dogs.3. The RBF responses to these vasoactive agents were unaltered by chronic intrarenal Angll infusion in conscious dogs.4. These functional studies provide no evidence for renal vascular hypertrophy in response to chronic intrarenal Angll infusion in conscious dogs.
SPECIAL ARTICLE: NON‐INVASIVE MEASUREMENT OF ENDOTHELIAL FUNCTION
Authors: Playford DA , Watts GF 
Published: June 2007

SUMMARY1. Endothelial dysfunction, due to reductions in nitric oxide (NO) action, is an early feature of macrovascular disease.2. Non‐invasive measurement of endothelial function may be assessed by postischaemic dilatation of forearm vessels, using plethysmography, or flow‐mediated dilatation of the brachial artery, using ultrasound.3. Brachial flow‐mediated dilatation reflects NO release and/or action more than forearm hyperaemia.4. These techniques have been used as surrogate measures of coronary endothelial function.5. Methodological, physiological and clinical aspects of the techniques are discussed.
EFFECTS OF NITRIC OXIDE SYNTHASE INHIBITION AND ENDOTHELIN ETA RECEPTOR BLOCKADE ON HAEMODYNAMICS IN HYPERTENSIVE RATS
Authors: Granstam S‐O , Lind L. , Granstam E. , Fellström B. 
Published: June 2007

SUMMARY1. The objectives of the present study were to study regional differences in haemodynamics between spontaneously hypertensive (SHR) and normotensive Wistar‐Kyoto (WKY) rats induced by the nitric oxide synthase (NOS) inhibitor NG‐monomethyl ‐l‐arginine (l‐NMMA) and the endothelin ETA receptor antagonist BQ123 in vivo in tissues known to be important for blood pressure (BP) regulation (heart, kidney and skeletal muscle). Furthermore, the effect of acetylcholine (ACh) infusion (2 μg/kg per min) was examined after l‐NMMA or BQ 123. The microsphere method was used for determinations of cardiac index (CI) and regional haemodynamics.2. NG‐Monomethyl‐l‐arginine (20mg/kg) increased BP (26–48%; P < 0.01) and reduced CI in both rat strains. BQ 123 (1 mg/kg) reduced BP slightly (‐4 to 11 %; P < 0.05).3. NG ‐Monomethyl‐l‐arginine significantly increased myocardial and skeletal muscle vascular resistance in SHR only; however, in the kidney, l‐NMMA reduced blood flow and increased vascular resistance in both rat strains.4. BQ 123 induced minor changes in regional haemodynamics that were not significantly different between the two strains.5. Acetylcholine following BQ123 induced an increase in myocardial blood flow in WKY rats, but decreased blood flow in SHR. Acetylcholine following l‐NMMA reduced myocardial blood flow in both strains.6. Acetylcholine following BQ 123 induced renal vasodilation in WKY rats but, following l‐NMMA, ACh did not induce renal vasodilation in either rat strain. In contrast, l‐NMMA did not abolish the vasodilation of acetylcholine in skeletal muscle in WKY rats.7. In conclusion, the contribution of nitric oxide to basal vessel tone was not impaired in the heart, skeletal muscle and kidney in SHR. Antagonism of ETA receptors caused similar haemodynamic responses in both rat strains in these organs. Furthermore, NOS inhibition, but not ETA blockade, blunted the expected ACh‐induced vasodilation in the heart and kidney in WKY rats, but not in skeletal muscle in both strains.
EMBRYONIC GLOBINS OF THE MARSUPIAL THE TAMMAR WALLABY (MACROPUS EUGENII): BIRD LIKE AND MAMMAL LIKE
Authors: Holland Robert AB , Gooley Andrew A. , Hope Rory M. 
Published: June 2007

SUMMARY1. Tammar Wallaby embryonic blood has been shown to have three α‐like and two β‐like globin chains in its four haemoglobin components and partial sequences of several chains have been determined.2. The major embryonic β‐like chain (ɛ) is similar to other mammalian embryonic p‐like chains on the basis of sequencing its first 60 amino acids.3. There is another embryonic β‐like chain present in one haemoglobin component. It was designated to and, in its first 54 amino acids, it has features that are more like avian globins than mammalian globins.4. The one α‐like embryonic globin sequenced has mammalian rather than avian characteristics.5. A provisional phylogenetic tree of β‐like globins has been determined. The Tammar ω‐globin forms a monophyletic group with marsupial and other mammalian embryonic globins; the to‐globin forms a monophyletic group with bird adult and embryonic globins.
STUDIES OF EVOLUTIONARY TEMPERATURE ADAPTATION: MUSCLE FUNCTION AND LOCOMOTOR PERFORMANCE IN ANTARCTIC FISH
Authors: Franklin Craig E. 
Published: June 2007

SUMMARY1. Studies of evolutionary temperature adaptation of muscle and locomotor performance in fish are reviewed with a focus on the Antarctic fauna living at subzero temperatures.2. Only limited data are available to compare the sustained and burst swimming kinematics and performance of Antarctic, temperate and tropical species. Available data indicate that low temperatures limit maximum swimming performance and this is especially evident in fish larvae.3. In a recent study, muscle performance in the Antarctic rock cod Notothenia coriiceps at 0°C was found to be sufficient to produce maximum velocities during burst swimming that were similar to those seen in the sculpin Myoxocephalus scorpius at 10°C, indicating temperature compensation of muscle and locomotor performance in the Antarctic fish. However, at 15°C, sculpin produce maximum swimming velocities greater than N. coriiceps at 0°C.4. It is recommended that strict hypothesis‐driven investigations using ecologically relevant measures of performance are undertaken to study temperature adaptation in Antarctic fish. Recent detailed phylogenetic analyses of the Antarctic fish fauna and their temperate relatives will allow a stronger experimental approach by helping to separate what is due to adaptation to the cold and what is due to phytogeny alone.
MOLECULAR AND STRUCTURAL BIOLOGY OF THYROID HORMONE RECEPTORS
Authors: Apriletti James W. , Ribeiro Ralff CJ , Wagner Richard L. , Feng Weijun , Webb Paul , Kushner Peter J. , West Brian L. , Nilsson Stefan , Scanlan Thomas S. , Fletterick Robert J. , Baxter John D. 
Published: June 2007

SUMMARY1. Thyroid hormone receptors (TR) are expressed from two separate genes (α and β) and belong to the nuclear receptor superfamily, which also contains receptors for steroids, vitamins and prostaglandins.2. Unliganded TR are bound to DNA thyroid hormone response elements (TRE) predominantly as homodimers, or as heterodimers with retinoid X‐receptors (RXR), and are associated with a complex of proteins containing corepressor proteins. Ligand binding promotes corepressor dissociation and binding of a coactivator.3. Recent studies from our group have focused on the acquisition and use of X‐ray crystallographic structures of ligand‐binding domains (LBD) of both the rat (r) TRα and the human (h) TRβ bound to several different ligands. We have also developed ligands that bind selectively to the TRβ, which may provide ways to explore the differential functions of TRα compared with TRβ isoforms.4. The LBD is comprised mostly of α‐helices. The ligand is completely buried in the receptor and forms part of its hydrophobic core. Kinetic studies suggest that the limiting step in formation of high‐affinity ligand‐receptor complexes is the rate of folding of the receptor around the ligand. Ligands can be fitted tightly in the ligand‐binding pocket and small differences in this fitting may explain many structure‐activity relationships. Interestingly, analysis of the structures of antagonists suggests that they have chemical groups, ‘extensions', that could impair receptor folding around them and, thus, prevent the agonist‐induced conformation changes in the receptor.5. The TR structures allowed us to see that the mutations that occur in the syndrome of generalized resistance to thyroid hormone are located in the vicinity of the ligand‐binding pocket.6. X‐ray structure of the TR has also been used to guide construction of mutations in the TR surface that block binding of various proteins important for receptor function. Studies with these TR mutants reveal that the interfaces for homo‐ and heterodimerization map to similar residues in helix 10 and 11 and also allow the definition of the surface for binding of coactivators, which appears to be general for nuclear receptors. Formation of this surface, which involves packing of helix 12 of the TR into a scaffold formed by helices 3 and 5, appears to be the major change in the receptor structure induced by hormone occupancy.
DEVELOPMENTAL BIOLOGY AT THE HOWARD FLOREY INSTITUTE
Authors: Beck Felix 
Published: June 2007

SUMMARY1. A brief account of the history of developmental biology at the Howard Florey Institute, as well as in a wider general context, is presented and some of the results of developmental studies performed at the Institute over the past 7 years are discussed.2. In the foetal rat, parathyroid hormone rather than parathyroid hormone‐related protein is produced by the parathyroid anlage. This contrasts with results reported by others for the sheep.3. The control of imprinting of H19 and insulin‐like growth factor‐II has been studied in the mouse using gene knockout of the coding region of the H19 gene. Bi‐allelic expression of H19 in some liver and gut cells was observed.4. Gene knockout of the homeobox gene Cdx2 produced dramatic effects. Homozygous embryos did not implant in the uterus. Heterozygotes exhibited homeosis involving the gut and skeleton. Animals developed intestinal tumours within a few weeks of birth.