bluuebunny/crossref_metadata_2025_split huggingface dataset:
β‐Adrenoceptor Blocking Activities Of Nipradilol And Its Optical Isomers In Pig Coronary Artery
Authors: Itomine Tatsushi , Matsuzaki Toshihiro , Sakanashi Mayuko , Hobara Norio , Sakanashi Matao 
Published: March 2003

SUMMARY1. β‐Adrenoceptor blocking activities of nipradilol, its four optical isomers (RR, RS, SR, SS) and denitro nipradilol were evaluated using pig isolated coronary arteries.2. (–)‐Isoprenaline produced concentration‐dependent relaxations of the arteries, which were antagonized by nipradilol, its four optical isomers or denitro nipradilol under KCl‐induced contracture.3. The order of pA2 values for β‐adrenoceptor blocking activities was SR > nipradilol > SS ≥ denitro nipradilol > RR > RS.4. The nitroxy group in nipradilol appears to enhance its β‐adrenoceptor blocking activity, because the β‐adrenoceptor blocking activity of nipradilol was more potent than that of denitro nipradilol.5. Isomers that have the S configuration (SR, SS) at the 2′ position (having a hydroxyl group) in the aryloxypropanolamine showed more potent β‐adrenoceptor blocking activity than isomers that have the R configuration (RR, RS).6. Isomers that have the R configuration (SR, RR) at the 3 position (having a nitroxy group) in the benzopyran ring showed more potent β‐adrenoceptor blocking activity than those with the S configuration (SS, RS).7. It is suggested that the difference in configuration of the chemical structure of nipradilol may result in variations of binding affinity for the β‐adrenoceptor.
The Lung Is The Major Site That Produces Nitric Oxide To Induce Acute Pulmonary Oedema In Endotoxin Shock
Authors: Lee Ru Ping , Wang David , Kao Shang Jyh , Chen Hsing I 
Published: March 2003

SUMMARY1. The present study was undertaken to determine the locus of nitric oxide (NO) production that is toxic to the lung and produces acute pulmonary oedema in endotoxin shock, to examine and compare the effects of changes in lung perfusate on endotoxin‐induced pulmonary oedema (EPE) and to evaluate the involvement of constitutive and inducible NO synthase (cNOS and iNOS, respectively).2. Experiments were designed to induce septic shock in anaesthetized rats with the administration of Escherichia coli lipopolysaccharide (LPS). Exhaled NO, lung weight (LW)/bodyweight (BW) ratio, LW gain (LWG) and lung histology were measured and observed to determine the degree of EPE 4 h following LPS. The EPE was compared between groups in which LPS had been injected either into the systemic circulation or into the isolated perfused lung. The lung perfusate was altered from whole blood to physiological saline solution (PSS) with 6% albumin to test whether different lung perfusions affected EPE. Pretreatment with various NOS inhibitors was undertaken 10 min before LPS to investigate the contribution of cNOS and iNOS to the observed effects.3. Endotoxin caused profound systemic hypotension, but little change in pulmonary arterial pressure. The extent of EPE was not different between that induced by systemic injection and that following administration to isolated lungs preparations. Replacement of whole blood with PSS greatly attenuated (P < 0.05) EPE. In blood‐perfused lungs, pretreatment with NOS inhibitors, such as Nω‐nitro‐L‐arginine methyl ester, aminoguanidine and dexamethasone, significantly prevented EPE (P < 0.05).4. The major site of NO production through the whole blood is in the lung. The NO production mediated by the iNOS system is toxic to the endothelium in the pulmonary microvasculature. Inhalation of NO for patients with sepsis may be used with clinical caution. Therapeutic consideration of lung extracorporeal perfusion with PSS and pharmacological pretreatment with iNOS inhibitors may be warranted.
Circumventricular Organs: Gateways to the Brain Role Of Circumventricular Organs (CVO) In Neuroendocrine Responses: Interactions Of Cvo And The Magnocellular Neuroendocrine System In Different Reproductive States
Authors: Summy‐Long Joan Y , Kadekaro Massako 
Published: March 2003

SUMMARY1. Magnocellular neurons, which release oxytocin (OT) or vasopressin (VP) into the circulation in response to hyperosmolality, hypovolaemia and cholecystokinin (CCK), undergo a resetting during pregnancy and lactation that involves circumventricular organs.2. During gestation, there is a similar lowering of the osmotic thresholds for stimulation of OT and VP release, whereas the responsiveness of both neuroendocrine systems to hyperosmolality is attenuated by lactation. These osmotic changes in the magnocellular system are mediated by depletion of hormone (OT) stores in the neurohypophysis (lactation), as well as by alterations in afferent stimulation via pathways involving the subfornical organ, organum vasculosum lamina terminalis and median preoptic nucleus.3. During gestation, both the VP and OT systems are reset such that the expanded blood volume is maintained and defended as ‘normal’ in response to hypovlaemia. Thus, in virgin animals, only a 0–5% reduction in blood volume is needed to activate VP release, whereas 23–25% is required for stimulation of the oxytocinergic system. Thereafter, incremental changes in plasma levels of both hormones with increasing loss in blood volume are similar in virgin and pregnant animals. However, during lactation, the apparent hypovolaemic threshold for both hormones becomes significantly elevated to 20.4% (VP) and > 25% (OT) blood volume depletion, resulting in a decreased responsiveness of the magnocellular system to hypovolaemia.4. The OT response to CCK is attenuated in lactating animals and circulating VP is unaffected in pregnant rats given the peptide.
General practitioner participation in the second australian national blood pressure study (ANBP2)
Authors: Reid Christopher M , Ryan Phillip , Nelson Mark , Beckinsale Paul , McMurchie Marilyn , Gleave David , DeLoozeƒ Fred , Wing Lindon M 
Published: March 2003

SUMMARY1. The second Australian National Blood Pressure Study (ANBP2) is an outcome trial of the treatment of hypertension in the elderly conducted entirely in general practices across Australia. Prior to ANBP2, no study of this size and nature had been undertaken in Australian general practice and the response of General Practitioners (GPs) to becoming involved in long‐term cardiovascular research was unknown.2. Academic departments and Divisions of General Practice were approached to support the project. General Practitioners were approached by letter of invitation and contacted by a regional medical coordinator (RMC) either at a face‐to‐face meeting or by telephone.3. At the close of recruitment to ANBP2, 1938 GPs from 950 practices had registered as investigators. Sixty‐two Divisions of General Practice were approached to support the study in five mainland Australian states with 39 (63%) participating, although participation by state was highly variable (range: 18–100%). Thirty divisional or promotional dinner meetings were held, with 56% (368/658) of those attending registering as investigators. Of the 8098 GPs sent a letter of invitation to participate in the study, 1357 (17%) expressed interest and eventually enrolled as investigators, ranging from 8% in Queensland to 28% in New South Wales. Ninety‐six per cent of GPs who had a personal face‐to‐face contact (696/724) with the RMC registered in the study.4. The GP recruitment phase of ANBP2 has been successfully completed. Peer‐to‐peer recruitment was the most successful strategy; however, success varied between states. General Practitioner recruitment to long‐term clinical trials appears to be successful with a multifactorial approach focusing on peer‐to‐peer recruitment.
Proceedings of the Australian Physiological and Pharmacological Society Symposium: New Frontiers in Muscle Research Hybrid skeletal muscle fibres: a rare or common phenomenon?
Authors: Stephenson Gabriela MM 
Published: March 2003

SUMMARY1. The main aim of the present review is to raise awareness of the molecular complexity of single skeletal muscle fibres from ‘normal’ and ‘transforming’ muscles, in recognition of the many types of hybrids that have been observed in vertebrate skeletal muscle. The data used to illustrate various points made in the review were taken from studies on mammalian (mostly rat) and amphibian muscles.2. The review provides a brief overview of the pattern and extent of molecular heterogeneity in hybrid muscle fibres and of the methodological problems encountered when attempting to identify and characterize such fibres. Particular attention is given to four types of skeletal muscle hybrids: (i) myosin heavy chain (MHC) hybrids; (ii) mismatched MHC–myosin light chains (MLC) hybrids; (iii) mismatched MHC–regulatory protein hybrids; and (iv) hybrids containing mismatched MHC–sarcoplasmic reticulum protein isoforms.3. Some of the current ideas regarding the functional significance, origin and cognitive value of hybrid fibres are examined critically.
Blood Pressure Variability And Organ Damage
Authors: Su Ding‐Feng , Miao Chao‐Yu 
Published: March 2003

SUMMARY1. Blood pressure variability (BPV) is expressed as the standard deviation of the average blood pressure (BP). Blood pressure variability is increased in hypertensive patients and animals. However, BPV is not necessarily related to the BP level.2. For nearly any level of 24 h mean BP, hypertensive patients in whom the BPV is low have a lower prevalence and severity of organ damage than patients in whom the 24 h BPV is high. This observation has been confirmed further in spontaneously hypertensive rats with direct pathological analysis for organ damage.3. In sinoaortic‐denervated (SAD) rats, 24 h average BP is normal and BPV is markedly increased. Myocardial damage, renal lesions and vascular remodelling are seen in these animals 4 weeks after SAD.4. Haemodynamic effects and activation of the renin– angiotensin system are hypothesized to contribute to organ damage induced by increased BPV.5. Blood pressure variability is of potential importance in antihypertensive therapy.
Fendiline Mobilizes Intracellular Ca2+ In Chang Liver Cells
Authors: Cheng Jin‐Shiung , Chou Kang‐Ju , Wang Jue‐Long , Lee Kam‐Chung , Tseng Li‐Ling , Tang Kwong‐Yui , Huang Jong‐Khing , Chang Hong‐Tai , Su Warren , Law Yee‐Ping , Jan Chung‐Ren 
Published: March 2003

SUMMARY1. The effects of the antianginal drug fendiline (N‐[3,3‐diphenylpropyl]‐α‐methyl‐benzylamine) on intracellular free Ca2+ levels ([Ca2+]i) in Chang liver cells were evaluated using fura‐2 as a fluorescent Ca2+ indicator.2. Fendiline (1–100 μmol/L) increased [Ca2+]i in a concentration‐dependent manner, with an EC50 of 25 μmol/L.3. The [Ca2+]i response was composed of an initial rise and a slow decay to a sustained phase. Removal of extracellular Ca2+ partly reduced the [Ca2+]i signals.4. Fendiline (10 μmol/L)‐induced release of intracellular Ca2+ was reduced by 65% following pretreatment with 1 μmol/L thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) to deplete Ca2+ stored in the endoplasmic reticulum.5. After pretreatment with 10 μmol/L fendiline in Ca2+‐free medium for several minutes, addition of 3 mmol/L Ca2+ induced an increase in [Ca2+]i of a magnitude four‐fold greater than control. This increase in [Ca2+]i was not reduced by 10 μmol/L SKF96365, econazole, nifedipine or verapamil.6. Fendiline (10 μmol/L)‐induced release of intracellular Ca2+ was not altered by inhibition of phospholipase C with 2 μmol/L 1‐(6‐((17β‐3‐methoxyestra‐1,3,5(10)‐trien‐17‐yl)amino) hexyl)‐1H‐pyrrole‐2,5‐dione (U73122).7. The results of the present study show that fendiline induces an increase in [Ca2+]i in Chang liver cells by releasing stored Ca2+ in an inositol 1,4,5‐trisphosphate‐independent manner and by causing extracellular Ca2+ influx.
Effect Of Age On Renal Functional And Orthostatic Vascular Response In Healthy Men
Authors: Adachi Toshiyuki , Kawamura Minoru , Owada Masahiko , Hiramori Katsuhiko 
Published: March 2003

SUMMARY1. Few studies have been reported concerning the effect of ageing on renal functional and vascular responses to various stresses during ordinary life. In the present study, we examined the effect of age on changes in renal sodium handling and renal vascular resistance (RVR) in response to standing from a supine position in subjects with normal renal function.2. We selected 43 healthy males in the second through to the seventh decade of life and gave them a constant dietary sodium intake before the study period. Renal function was estimated by standard clearance methods with the subject in a state of euvolaemia.3. The mean daily urinary excretion of sodium was 236 ± 22 mEq. Standing from a supine position was associated with significant decreases (P < 0.0001) in creatinine clearance (from 125 ± 18 to 117 ± 19 mL/min per 1.73 m2), sodium excretion (from 178 ± 29 to 97 ± 23 μEq/min) and fractional excretion of sodium (from 1.02 ± 0.19 to 0.60 ± 0.13%). A significant increase (P < 0.0001) in the RVR index (from 0.11 ± 0.03 to 0.14 ± 0.04 units) was noted. Univariate analysis indicated that while the change in RVR associated with standing was significantly diminished (P < 0.05) in older subjects, orthostatic changes in other parameters associated with standing were minimally influenced by age.4. In conclusion, although the renal vascular response is impaired in advanced age, the renal functional response to orthostasis is otherwise maintained in healthy elderly subjects under conditions of normal sodium intake and clinical euvolaemia.
The Selfish Brain And The Barker Hypothesis
Authors: Lumbers Eugenie R , Yu Ze‐Yan , Gibson Karen J 
Published: March 2003

SUMMARY1. Brain sparing is a feature of intra‐uterine growth retardation (IUGR). This implies that there is a redistribution of metabolic supply so that body growth slows to a greater extent than brain growth.2. Intra‐uterine growth retardation, as evidenced by a low birthweight for gestational age is a predisposing factor for hypertension, cardiovascular disease and diabetes mellitus in adult life.3. In species like humans, nephrogenesis is complete before birth. In the rat, it is completed shortly after birth. In both species, it can be shown that either undernutrition or IUGR is associated with reduced nephron number.4. It has been proposed that oligonephropathy results in hyperfiltration, which ultimately leads to glomerulosclerosis and hypertension. The renin–angiotensin system (RAS) is necessary for normal renal development and fetal renal function. In the rat, blockade of the RAS in the first weeks of life by pharmacological agents reduces glomerular number and has been shown to cause hypertension in adult life. Renal denervation reduces the activity of the fetal RAS and also causes abnormal development of the renin‐secreting cells.5. There is tonic renal sympathetic nerve activity in the late gestation fetal sheep. The level of renal sympathetic nerve activity (RSNA) is influenced by the fetal behavioural state.6. However, interactions between the developing kidney and the developing sympathetic nervous system are poorly understood. On the one hand, renal innervation may be important in the provision of neurotrophic factors that stimulate the development of the RAS and kidney. On the other, high levels of RSNA associated with circulating catecholamines and vasopressin may cause vasoconstriction and limit nephrogenesis. This latter effect could be a predisposing factor to adult hypertension and cardiovascular disease.
Characterization Of Lymphocyte β2‐Adrenoceptor Signalling In Patients With Left Ventricular Volume Overload Disease
Authors: Dzimiri Nduna , Basco Chona , Moorji Azadali , Afrane Barima , Al‐Halees Zohair 
Published: March 2003

SUMMARY1. Studies using animal experimental models have suggested that the β2‐adrenoceptor
is uncoupled in association with alterations in the expression of G‐protein‐coupled
receptor kinases (GRK) 2/3 in heart failure. However, the functional expression of
the components of this pathway in human disease has not been fully elucidated yet.
In the present study, we evaluated the possibility that the regulation of β2‐adrenoceptor signalling components in patients with left ventricular volume overload (VOL) depends on the severity of the overload.2. We characterized the lymphocyte GRK 2–6, β‐arrestins 1 and
2, β2‐adrenoceptor expression at the mRNA and protein levels, as well as the activity of adenylyl cyclase, protein kinases (PK) A and PKC in patients with VOL using healthy blood donors as controls.3. In the patient group, GRK2 mRNA was increased by 61% (P <
0.001), GRK3 was increased by 54% (P < 0.005), GRK5 was increased
fivefold (P < 0.001) and the β‐arrestin 2 mRNA was increased
by 40% (P < 0.05). These increases were paralleled with a sixfold
increase in GRK2, a twofold increase in GRK3 and a 1.3‐fold increase in GRK5 protein
levels. These changes were associated with a significant decrease in β2‐adrenoceptor mRNA, the basal, catalytic and receptor‐mediated activity of adenylyl cyclase and sensitization of the forskolin‐stimulated activity towards augmented inhibition by guanylimidodiphosphate. In general, the increase in GRK2 and 5 mRNA exhibited a positive correlation with the gravity of the haemodynamic load, as determined by changes in left ventricular fractional shortening.4. The results suggest that VOL induces an increase in the expression of lymphocyte β2‐adrenoceptor‐specific GRK and β‐arrestin 2
in association with an attenuation in β2‐adrenoceptor levels.
It can be speculated that the cardiac circulatory system adapts itself to altered
haemodynamic functional demands partly by altering β2‐adrenoceptor signalling.
A Comparative Study On The Activity Of Lansoprazole, Omeprazole And PD‐136450 On Acidified Ethanol‐ And Indomethacin‐Induced Gastric Lesions In The Rat
Authors: Chandranath SI , Bastaki SMA , Singh J 
Published: March 2003

SUMMARY1. The proton pump inhibitors lansoprazole (LP) and omeprazole (OP) and the cholecystokinin (CCK)‐receptor antagonist PD‐136450 (PD) provide a broad spectrum of activities in their ability to inhibit gastric acid secretion and protect the stomach against ulcerogens. In the present study, we investigated the protective effects of these compounds against gastric ulcers induced by acidified ethanol (AE) and indomethacin.2. Both AE (60% ethanol in 150 mmol/L HCl, 1 mL/rat) and indomethacin (30 mg/kg) produced gastric haemorrhagic lesions in the rat 1 and 6 h after oral administration, respectively.3. The gastric mucosal protective effects of LP (1–20 mg/kg), OP (0.5–10 mg/kg) and PD (1–20 mg/kg), administered either orally or subcutaneously (s.c.) 30 min before the administration of AE or indomethacin, were dose dependent against both models of ulcer induction.4. To determine whether the cytoprotective effect of LP, OP and PD (each 10 mg/kg) was mediated by endogenous prostaglandins (PG), indomethacin (10 mg/kg, s.c.) was administered 15 min before AE to inhibit prostanoids biosynthesis. Indomethacin reduced the cytoprotective effects of OP, but not LP, administered either orally or s.c. Indomethacin reduced the cytoprotective effect of PD administered orally, although the effect was much less significant than when PD was administered s.c. The results exclude the role of PG in mediating the protective effects of LP, whereas the possibility exists for PG to have a role in mediating the protective effects of OP and PD.5. To investigate the possible involvement of endogenous nitric oxide (NO) in the cytoprotective action of LP, OP and PD, we treated rats with a selective inhibitor of NO synthesis, namely NG‐nitro‐L‐arginine methyl
ester (L‐NAME; 25 mg/kg, s.c.). Administration of L‐NAME
15 min prior to LP, OP or PD (each 10 mg/kg) orally or s.c. and challenge with AE
or indomethacin did not significantly increase the degree of the ulcer index and
L‐NAME was not able to antagonize the protective effects of LP, OP
and PD, thus excluding the role of NO in mediating the protective effects of these
drugs. However, the effects of PD in reducing the indomethacin‐induced ulcer index
were less significant in the presence than the absence of L‐NAME (P
< 0.05 vs P < 0.001, respectively), suggesting a role for NO.6. In conclusion, the results of the present study suggest that LP and OP are equally effective against AE‐ as well as indomethacin‐induced gastric ulcers and were more potent than PD in protecting the stomach against ulcer formation. Lansoprazole, OP and PD bring about their cytoprotective action through the reduction of acid secretion and some other unknown mechanisms. However, OP and PD may exert their cytoprotective action through PG and NO pathways.
Potassium Channels Underlying The Resting Potential Of Pulmonary Artery Smooth Muscle Cells
Authors: Gurney Alison M , Osipenko Oleg N , MacMillan Debbi , Kempsill Fiona EJ 
Published: March 2003

SUMMARY1. The molecular identity of the K channels giving rise to the negative membrane potential of pulmonary artery smooth muscle cells has yet to be determined.2. To date, most studies have focused on voltage‐gated, delayed rectifier channels and their roles in mediating hypoxia‐induced membrane depolarization. There is, however, strong evidence that an outwardly rectifying K+ conductance distinct from the classical delayed rectifier is involved.3. Growing evidence that TASK‐like channels can sense hypoxia and are present in pulmonary artery smooth muscle cells suggests that they may be responsible for the resting K+ conductance and resting potential.4. The present review considers the evidence that particular K channels maintain the resting membrane potential of pulmonary artery smooth muscle cells and mediate the depolarizing response to hypoxia.
Effects Of Glycine On Glomerular Filtration Rate And Segmental Tubular Handling Of Sodium In Conscious Rats
Authors: Thomsen Klaus , Nielsen Camilla Birch , Flyvbjerg Allan 
Published: March 2003

SUMMARY1. Infusion of the amino acid glycine leads to an increase in effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by a mechanism that possibly involves stimulation of nitric oxide (NO). Because NO also increases proximal tubular fluid output (Vprox) by inhibition of proximal tubular Na+ reabsorption and modulation of the tubuloglomerular feedback system, we hypothesized that glycine would increase Vprox as measured by lithium clearance (CLi).2. In the first series of experiments, the effect of glycine infusion (4 mg/min) was examined in conscious, unstressed, chronically catheterized rats. In an additional series of experiments, the effect of glycine was examined under similar conditions in rats pretreated with a NO synthase (NOS) inhibitor (NG‐nitro‐L‐arginine methyl ester (L‐NAME), 2.5 μg/min).3. Glycine significantly increased ERPF (from 3268 to 4018 μL/min per 100 g bodyweight (BW)), GFR (from 874 to 1009 μL/min per 100 g BW), CLi (from 275 to 461 μL/min per 100 g BW) and Na+ clearance (CNa; from 2.9 to 14.0 μL/min per 100 g BW). Fractional excretion of lithium (FELi; from 32 to 46%) and CNa/CLi (from 0.99 to 2.99%) also rose, indicating inhibition of proximal and distal nephron Na+ reabsorption, respectively. In the rats pretreated with L‐NAME, similar haemodynamic and tubular responses to glycine infusion were seen, suggesting that the effects were not mediated by NO.4. We conclude, that glycine increases ERPF and GFR and it also inhibits proximal and distal nephron Na+ reabsorption leading to an increase in CLi and CNa. There was no indication that any of these effects were mediated by NO.