bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF INDOMETHACIN ON EPIDERMAL GROWTH FACTOR‐INDUCED RENAL RESPONSES IN SHEEP
Authors: Gow Christine B. , Grant Sharon L. , Phillips Paddy A. 
Published: June 2007

SUMMARY1. The effects of indomethacin (an inhibitor of prostaglandin synthesis) on the renal responses to epidermal growth factor (EGF) were investigated in conscious sheep.2. Ewes (n = 5 per group) received an i.v. saline infusion (150 mL/day) for days 1‐8, followed by either vehicle control, 15 μg/h EGF, 2mg/kg per day indomethacin or 15 μg/h EGF with 2 mg/kg per day indomethacin in 150 mL/day saline, i.v., over days 9‐12. All ewes subsequently received an i.v. saline infusion (150 mL/day) over days 13‐20.3. Polydipsia, diuresis, transient natriuresis and reduced urine osmolality occurred during EGF treatment alone. There was no effect of EGF on fluid balance, plasma electrolyte or hormone concentrations, plasma osmolality or haematocrit or on the urinary excretion of potassium.4. Simultaneous infusion of indomethacin with EGF attenuated (P>0.05) the stimulatory effects of EGF infusion alone on urine volume, water intake, natriuresis and urine osmolality.5. We conclude that prostaglandins may be involved in the diuretic/natriuretic effects of EGF, but may not be the sole mechanism involved.
LOSARTAN AND CAPTOPRIL FOLLOW DIFFERENT MECHANISMS TO DECREASE PRESSOR RESPONSES IN THE PITHED RAT
Authors: Yokoyama Hitomi , Minatoguchi Shinya , Koshiji Masatoshi , Uno Yoshihiro , Kakami Masao , Nagata Chisato , Ito Hiroyasu , Fujiwara Hisayoshi 
Published: June 2007

SUMMARY1. We investigated the effects of losartan and captopril on noradrenaline (NA) release and vascular reactivity to NA in the pithed rat.2. The pressor responses to sympathetic nerve stimulation (SNS) before and after i.v. administration of captopril (1 mg/kg), losartan (1 and 10 mg/kg), sodium nitroprusside (SNP; 5 μg/kg per min), losartan (1 mg/kg) + captopril (1 mg/kg), captopril (1 mg/kg) + losartan (1 mg/kg) or the bradykinin B2 receptor antagonist HOE 140 (1 mg/kg) + captopril (1 mg/kg) were measured. Plasma NA concentrations were measured during 60 s SNS before and after losartan (1 mg/kg), captopril (1 mg/kg), SNP (5 μg/kg per min) or HOE 140 (1 mg/kg) + captopril (1 mg/kg). Pressor responses to exogenous NA were measured before and after administration of losartan (1 mg/kg), captopril (1 mg/kg), HOE 140 (1 mg/kg) + captopril (1 mg/kg) or the nitric oxide synthase (NO) inhibitor, NG‐nitro‐L‐arginine methyl ester (L‐NAME; 10 mg/kg) + captopril (1 mg/kg).3. Captopril, losartan and SNP decreased frequency‐response curves to a similar extent. The captopril‐induced decrease in pressor responses to SNS was restored by pretreatment with HOE 140. Adding captopril to losartan decreased the curve more than did adding losartan to captopril. Both losartan, captopril and HOE 140 + captopril significantly decreased the plasma NA concentration after SNS (34.1±5.0, 27.4±2.6 and 41.4+8.1%, respectively). Sodium nitroprusside did not change the plasma NA concentration after SNS (3.8±28.2%). The dose‐response curves to i.v. NA were not affected by losartan, but were significantly decreased by captopril. However, responses to NA that were reduced by captopril were restored to control values by pretreatment with HOE 140 or L‐NAME.4. We suggest that both losartan and captopril decrease pressor responses to SNS by inhibiting NA release from sympathetic nerve endings; however, captopril also decreases ‘vascular reactivity’ to NA, which is mediated by nitric oxide produced by activation of the bradykinin B2 receptors.
HISTOLOGICAL EVALUATION OF CONNECTIVE TISSUE COMPONENTS IN THE HEALING PROCESS OF HUMAN GASTRIC ULCER
Authors: Miyata Akihiro , Goto Hidemi , Niwa Yasumasa , Hayakawa Tetsuo , Nagasaka Tetsuro , Nakashima Nobuo 
Published: June 2007

SUMMARY1. The aim of the present study was the evaluation of human gastric ulcer healing and intractability from the viewpoint of connective tissue components.2. Based on investigations of clinical status, we divided 78 patients with a gastric ulcer into three groups. All patients underwent gastrectomy and group I consisted of 17 patients operated on for bleeding or perforation, group II consisted of 37 patients operated on for an accompanying gastric carcinoma and group III consisted of 24 patients operated on for ulcer intractability.3. We evaluated, in resected specimens, angiogenesis by Azan‐Mallory staining and fibroplasia by applying proliferating cell nuclear antigen (PCNA) immunostaining. The inflammatory grade and fibrosis at the ulcer base were also evaluated by haematoxylin‐eosin and Azan‐Mallory staining.4. Microvessel counts in group III were significantly lower than those in groups I and II (P<.05). The PCNA labelling index of fibroblasts in group III was significantly lower than that in groups I and II (P>0.05). The inflammatory grade was severe and fibrosis was excessive in group III.5. From these results, it is suggested that the reduced angiogenesis and decline in fibrous cell proliferation are important factors contributing to gastric ulcer intractability.
SHORT COMMUNICATION HYPOTENSIVE EFFECTS OF PEPTIDE T IN CONSCIOUS RATS
Authors: Wen Cheng , Liu Dennis T. , Li Ming , Michaelis Jurgen , Grigg Geoffrey W. , Whitworth Judith A. 
Published: June 2007

SUMMARY1. The present study investigated the effects of peptide T on mean arterial blood pressure (MAP) in conscious normotensive Sprague‐Dawley (SD) rats, spontaneously hypertensive rats (SHR) and two‐kidney one‐clip (2K1C) hypertensive rats.2. Peptide T was infused via the left jugular vein at a rate of 1 mg/kg per h in SD, SHR and 2K1C rats and then at doses of 0.1, 0.25, 0.5,1 and 5 mg/kg per h in SHR, with 0.9% saline as a sham control in SHR and 2K1C. Mean arterial pressure was measured directly before, during and after infusion.3. Peptide T (1 mg/kg per h) decreased blood pressure in both SHR (/><0.01) and 2K1C (P<0.05). In normotensive SD rats the fall in MAP approached statistical significance (P = 0.06). The effect of peptide T was not significantly different in normotensive compared with hypertensive rats. Saline infusion had no effect. The blood pressure lowering effect of peptide T appeared to be dose‐dependent in SHR.
Ming Li, Tafline Fraser, Jian Wang* and Judith A Whitworth
Authors: Ming Li  , Tafline Fraser  , Jian Wang  , A Whitworth Judith 
Published: June 2007

SUMMARY1. The effects of L‐arginine treatment on dexamethasone‐induced hypertension were examined in the Sprague‐Dawley rat Seventy rats were randomly divided into the following eight groups: sham, dexamethasone (5 and 10 fig/day), L‐arginine (100 and 500 mg/kg per day), L‐arginine (100 or 500 mg/kg per day) + dexamethasone (10 ug/day), L‐arginine (520‐797 mg/kg per day in food) + dexamethasone (5 fig/day). Systolic blood pressure (SBP), bodyweight and plasma nitrate/nitrite concentration were measured.2. Dexamethasone (5 and 10 ug/day) increased SBP in both sham and L‐arginine‐treated rats. Dexamethasone at 10 ug/day decreased bodyweight, but did not alter plasma nitrate/nitrite concentrations.3. L‐Arginine (500 mg/kg per day, i.p.) increased plasma nitrate/nitrite concentrations in 10 ug/day dexamethasone‐treated rats. L‐Arginine did not alter blood pressure in either sham or dexamethasone‐treated rats.4. Dexamethasone‐induced hypertension differs from adrenocorticotropic hormone (ACTH)‐induced hypertension in the rat in that it is not modified by L‐arginine. Thus, ACTH‐induced hypertension cannot be explained simply in terms of glucocorticoid activity.
SHORT COMMUNICATION EXPRESSION OF THE 03‐ADRENOCEPTOR GENE POLYMORPHISM (Trp64Arg) IN OBESE DIABETIC AND NON‐DIABETIC SUBJECTS
Authors: Jeyasingam Cheryl L. , Bryson Janet M. , Caterson Ian D. , Yue Dennis K. , Donnelly Richard 
Published: June 2007

SUMMARY1. A missense mutation (Trp64Arg) in the (β3‐adrenoceptor (P3‐AR) gene has been associated with weight gain, insulin resistance and earlier‐onset non‐insulin‐dependent diabetes mellitus (NIDDM), but the strength of these associations varies considerably between populations and the functional significance of Trp64Arg remains unclear.2. The Trp64Arg mutation was investigated in obese NIDDM (= 50) and obese non‐diabetic (n = 53) subjects by polymerase chain reaction (PCR) amplification of genomic DNA and digestion of the 210 bp product by BstOI. The Arg allele was found in 22.3% of all subjects, but there were no homozygotes for the mutation. Non‐diabetic subjects heterozygous for the mutation were more obese and Trp/Arg diabetics had a slightly younger age of onset of NIDDM (47 vs 51 years, respectively), but there were no significant differences in mutation frequency between the two groups. Metabolic parameters (e.g. fasting lipids and glycaemic control) were similar among diabetic subjects with and without the Trp64Arg mutation.3. In conclusion, the frequency of the Trp64Arg mutation of the fb‐AR was higher in this obese population compared with some previous studies, but there was no evidence that Trp64Arg confers an increased susceptibility to NIDDM among obese insulin‐resistant subjects or that diabetics with the mutation fare worse in terms of lipid or glucose metabolism.
SHORT COMMUNICATION URIC ACID PERMEABILITY COEFFICIENT IN THE RAT PAPILLARY COLLECTING DUCT
Authors: Ray Cheryl , Carney Shane , Morgan Trefor 
Published: June 2007

SUMMARY1. While it is believed that the mammalian distal nephron is not involved in uric acid transport, this has not been directly evaluated. Nevertheless, some studies are consistent with significant distal nephron transport.2. As uric acid transport in man may be similar to the rat, unidirectional uric acid permeability was evaluated by perfusion of the isolated rat papillary collecting duct.3. Uric acid permeability was 0.61 ±0.04 μm/s, which was similar to sodium permeability (0.66 ±0.05 μm/S) but was less than chloride permeability (0.93 ±0.07 μn/s) and markedly less than water permeability (4.81 ±0.21 μm/s). Uric acid permeability was not changed following the addition of a maximal antidiuretic concentration of arginine vasopressin (200 μU/mL), nor was it changed by altering the uric acid concentration in the perfusate and bath.4. These results demonstrate that the papillary collecting duct is permeable to uric acid. The coefficient of transport is sufficiently low and insensitive to arginine vasopressin and uric acid concentrations to suggest that any transport that occurs is probably passive and only of minor physiological significance.
NITRIC OXIDE AS A MODULATOR OF MEDULLARY PATHWAYS
Authors: Lawrence Andrew J. 
Published: June 2007

SUMMARY1. The present study has employed in vitro electrophysiology and chemical neuroanatomy to determine whether nitric oxide (NO) could be considered a modulator at neurons involved in medullary cardiovascular control pathways.2. The NO donor diethylamine‐NO caused concentration‐related depolarizations of the rat isolated nodose ganglion preparation that were sensitive to blockade by inhibitors of soluble guanylate cyclase.3. Incubation of rat medulla oblongata sections (50 (JLITI) with a polyclonal antibody to NO synthase (NOS) revealed a topographic network of NOS‐containing neurons. Specifically, NOS‐positive neurons were found throughout the entire rostral‐caudal axis of the nucleus tractus solitarius (NTS) and also in the area postrema, dorsal motor nucleus of the vagus, nucleus ambiguus, caudal and rostral ventrolateral medulla, nucleus gigantocellularis and lateral paragigantocellularis.4. These data indicate that NO has functional actions on centrally projecting rat vagal afferent neurons that ultimately innervate the NTS. Furthermore, neurons that contain the enzyme NOS and that are, therefore, capable of using NO are localized in medullary nuclei concerned with both parasympathetic and sympathetic cardiovascular control pathways.
DIABETIC VASCULAR COMPLICATIONS
Authors: Cooper Mark E. , Gilbert Richard E. , Jerums George 
Published: June 2007

SUMMARY1. Diabetic vascular complications can be arbitrarily divided into micro‐ and macrovascular complications, the major microvascular complications being nephropathy, retinopathy and neuropathy. Macrovascular complications are due to accelerated atherosclerosis and include ischaemic heart disease, cerebrovascular disease and peripheral vascular disease.2. It is postulated that metabolic and haemodynamic factors interact leading to the development of diabetic vascular complications.3. Advanced glycation appears to be an important pathway in the pathogenesis of diabetic complications with evidence that the inhibitor of this process, aminoguanidine, attenuates the development of a range of diabetic vascular complications.4. The results of experimental studies have led to large‐scale clinical trials of various therapeutic agents that act to interfere with the metabolic and haemodynamic pathways implicated in the progression of diabetic complications.
EFFECTS OF LOCALLY ADMINISTERED ARGATROBAN ON RESTENOSIS AFTER BALLOON ANGIOPLASTY: EXPERIMENTAL AND CLINICAL STUDY
Authors: Imanishi Toshio , Arita Mikio , Tomobuchi Yoshiaki , Hamada Masanori , Hano Takuzo , Nishio Ichiro 
Published: June 2007

SUMMARY1. This study was undertaken to evaluate the preventive effects of locally administered argatroban, a competitive inhibitor of thrombin‐induced platelet activation, on restenosis after balloon angioplasty.2. A hydrogel‐coated balloon catheter was immersed three times in argatroban/saline solution (1 mg/mL) for 60 s, inflated to a pressure of 606 kPa and left in the rabbit common carotid artery for 1 min. The same procedure was performed, without drug, as a control. The pharmacokinetics of delivered argatroban in the arterial wall were assessed using [14C]‐argatroban. Platelet deposition 2h after balloon injury was quantified by fluorescence studies using antiplatelet antibody. Vascular smooth muscle cell (VSMC) proliferation 3 days after balloon injury was assessed by immunohistochemical staining for proliferative cell nuclear antigen (PCNA). In a clinical study, we divided 50 elective patients into two groups: argatroban and control.3. In the experimental study, the mean quantities of argatroban at 0, 2 and 6 h after deflation wer. 24.63, 0.49 and 0.11 nmol/g wet weight of artery, respectively. Argatroban was undetected 24 h after deflation. Two hours after deflation, argatroban‐treated arteries showed less platelet adhesion than saline‐treated controls. The mean number of PCNA‐positive cells was 16.9 and 43.8% in the argatroban and control groups, respectively (P < 0.01). In the clinical study, the mean late gain loss was 8.2 and 27.3% in the argatroban and control groups, respectively (P < 0.05). The mean late restenosis rate was 11.1 and 41.4% in the argatroban and control groups, respectively (P<0.05).4. These data suggest that blood coagulation plays a significant role in VSMC proliferation after balloon injury and that locally administered argatroban using hydrogel‐coated balloon catheter may prevent post‐percutaneous transluminal coronary angioplast. restenosis.
EFFECTS OF INTRACELLULAR Ca2+ CHELATING ON NORADRENALINE RELEASE IN NORMOXIC AND ANOXIC HEARTS
Authors: Du Xiao‐Jun , Bobik Alex , Esler Murray D. , Dart Anthony M. 
Published: June 2007

SUMMARY1. Ischaemia and anoxia induce excessive noradrenaline (NA) release in the heart by a mechanism independent of both nerve activity and extracellular Ca2+. The present study was designed to examine the potential role of intracellular Ca2+ mobilization in anoxic NA release in the heart by chelating intracellular free Ca2+.2. In normoxic hearts, preloading with an intracellular fre. Ca2+ chelator (BAPTA) reduced neuronal NA release by 65%, confirming the effectiveness of the loading protocol. Release of NA independent of nerve activity occurred in hearts subjected to a 40 min period of anoxic, substrate‐free and nominal Ca2+‐free perfusion. Loading hearts with BAPTA prior to anoxia failed to reduce NA overflow (1561 ± 147 vs 1496 ± 206 pmol/g over 40 min). Infusion with BAPTA (20 μmol/L) during the first 25 min of the anoxic period reduced the quantity of anoxic NA release by approximately 25% from 2013 ± 124 to 1476 ± 207 pmol/g (P < 0.05).3. Our results confirm that anoxic NA release is predominantly. Ca2+‐independent process with Ca2+ mobilization from endogenous storage playing only a minor contributing role.
EFFECTS OF AE0047 ON CEREBRAL ISCHAEMIA AND OEDEMA AFTER MIDDLE CEREBRAL ARTERY OCCLUSION IN CATS
Authors: Shinyama Hiroshi , Hayashi Kazutaka , Kawamura Toru , Nakamura Norifumi , Kagitani Yoshio 
Published: June 2007

SUMMARY1. AE0047 is a new dihydropyridine calcium antagonist with protective effects against cerebral ischaemia and the occurrence of stroke in several animal models.2. In the present study we investigated whether AE0047 would improve the reduced cerebral blood flow (CBF) and oedema formation in cats subjected to middle cerebral artery (MCA) occlusion and compared it for efficacy with other dihydropyridine calcium antagonists with different moieties, such as nilvadipine an. nicardipine.3. Middle cerebral artery occlusion reduced local CBF (1CBF), as measured by the hydrogen clearance method, while dry weight measurement showed that water content in the cortical tissues surrounding each 1CBF measurement electrode had increased after 4 h ischaemia.4. Both AE0047 (10 μg/kg) and nilvadipine (30 μg/kg), given intravenously 20min after MCA occlusion, produced an approximate 10. hypotensive response and significantly increased 1CBF in severely and moderately ischaemic regions, grouped according to the initial reduced flow values. However, nicardipine (5 μg/kg bolus followed by infusion of 3 μg/kg per min for 60 min) failed to mitigate the reduction in 1CBF despite an increase in the ICBF of the contralateral cortex. In addition, AE0047 tended to prevent an increase in cortical water content in severely ischaemic regions, whereas water content in both nilvadipine‐ and nicardipine‐treated groups tended to increase.5. These results suggest that dihydropyridine calcium antagonists act differently on cerebral ischaemia and oedema formation in a manner dependent on their side‐chain structures and that AE0047 effectively attenuates ischaemic brain damage without aggravatin. oedema.
ADRENALECTOMY OVERCOMES THE BLUNTED NATRIURETIC RESPONSE TO ATRIAL NATRIURETIC PEPTIDE DURING HYPOCAPNIA IN RATS
Authors: Kanauchi Hajime , Mimura Yoshikazu 
Published: June 2007

SUMMARY1. Hypocapnia has been shown to blunt the natriuretic effect of atrial natriuretic peptide (ANP) independently of the renal nerves. In order to examine whether the adrenal glands are a limiting factor for the natriuretic effect of ANP, we evaluated the natriuretic responses of adrenalectomized rats to ANP infusion during hypocapnia.2. Rats subjected to total adrenalectomy (ADX) or sham‐operation (sham) were divided into hypocapnic and normo‐capnic groups depending on their arteria. PCO2 levels.3. In sham rats, ANP infusion at a rate of 12 μg/kg per h resulted in a smaller increase in the fractional excretion of sodium during hypocapnia (mean±SEM: 1.02±0.40%, n = 10) than normocapnia (3.95±0.64%, n = 9; P < 0.001). The level of fractional excretion of sodium with ANP infusion during hypocapnia was not significantly different from the level in saline‐infused hypocapnic sham rats (0.93 ±0.62%, n= 10). In hypocapnic ADX rats (n= 11), ANP induced greater increases in the fractional excretion of sodium (5.59±1.35%) than did saline infusion (1.04+1.02%, n= 10; P < 0.002). In the absence of adrenal glands, the magnitude of natriuresis after ANP infusion during hypocapnia and normocapnia (3.32 ±1.07%, n = 9) were the same.4. We conclude that the natriuretic effect of ANP is blunted during hypocapnia in the presence, but not in the absence, of adrenal glands. Our data suggest that the adrenal glands have an important role in limiting the natriuretic effect of ANP.
DRUG DISPOSITION IN MOTHER AND FOETUS
Authors: Morgan Denis J. 
Published: June 2007

SUMMARY1. In pregnancy, plasma protein binding of certain drugs is reduced due to a reduction in serum albumin concentration. Due to an increase in cardiac output in pregnancy there is a 50% increase of effective renal plasma flow, glomerular filtration rate and creatinine clearance. This results in a corresponding increase in renal drug clearance.2. Placental transfer of small lipophilic molecules from the mother to the foetus is efficient because the placental membrane is a very thin lipophilic membrane, with a large surface area for exchange and high maternal and foetal placental blood flow rates. Nevertheless, placental transfer of relatively hydrophilic molecules is slow and this may limit foetal exposure to the drug where a single maternal dose is concerned.3. Once a drug has crossed the placenta it passes via the umbilical vein to the foetal liver and then to the systemic circulation of the foetus, which creates a potential foetal hepatic first‐pass effect. The activity of most foetal hepatic drug‐metabolizing enzymes studied is much less than the adult activity and some enzymes do not appear to be expressed at all. The circulation of the foetal liver is unique because 30–70% of umbilical vein flow is shunted via the ductus venosus. There is also a difference in oxygenation and enzyme content between the left and right lobes of the foetal liver.4. The foetal kidney is not a very effective route of elimination because renally excreted drug enters the amniotic fluid and recirculates via foetal swallowing. Moreover, foetal renal blood flow is only 3% of cardiac output, compared with 25% in the adult, and renal tubular anion secretion is absent. In conclusion, the extent of foetal exposure of maternally administered drug depends on numerous factors, in particular maternal and foetal elimination mechanisms and placental permeability.
CORONARY ENDOTHELIAL FUNCTION IN OPEN HEART SURGERY
Authors: He Guo‐Wei 
Published: June 2007

SUMMARY1. During open heart surgery, the heart is arrested and protected by hyperkalaemic cardioplegia. The coronary endothelium may be damaged by ischaemia‐reperfusion and cardioplegia. Subsequently, this may affect cardiac function immediately after cardiac surgery and cause mortality or morbidity.2. Our studies have investigated coronary endothelial function after exposure to hyperkalemi. (K+ 20 or 50 mmol/L). Endothelium‐dependent relaxation and hyperpolarization of the coronary smooth muscle and intracellular free calcium concentration in the endothelial cell were measured with regard to K+ exposure.3. Endothelium‐derived hyperpolarizing factor (EDHF)‐mediated relaxation to A23187, bradykinin, and substance P in the presence of either U46619 (10 nmol/L)‐ o. K+ (25 mmol/L)‐induced contraction was reduced after exposure to either 20 or 50mmol/LK.+4. The hyperpolarization of the membrane potential in response to the endothelium‐derived relaxing factor (EDRF) stimuli was also reduced by exposure t. K+.5. The intracellular free calcium concentration remained unchanged after exposure t. hyperkalemia.6. We conclude that the EDHF‐mediated coronary endothelial function is impaired after exposure to hyperkalaemic cardioplegia. The impairment of this function is due to the changed effect of EDHF on the smooth muscle cell, probably through partially depolarizing the membrane and affecting K+ channels rather than alteration of its biosynthesis/release in the endothelial cell. It may be of use to search for a new cardioplegia that preserves this endothelial function during open heart surgery.