bluuebunny/crossref_metadata_2025 huggingface dataset:
Ming Li, Tafline Fraser, Jian Wang* and Judith A Whitworth
Authors: Ming Li  , Tafline Fraser  , Jian Wang  , A Whitworth Judith
Published: June 2007

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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.
PLASMA CONCENTRATION OF BRAIN NATRIURETIC PEPTIDE IS RELATED TO DIASTOLIC FUNCTION IN HYPERTENSION
Authors: Cheung Bernard MY
Published: June 2007

1. The plasma brain natriuretic peptide (BNP) concentration is elevated in patients with essential hypertension and normal systolic function. This may be related to left ventricular hypertrophy or diastolic dysfunction, both of which commonly occur in hypertension.

2. Echocardiography was performed on 32 patients with newly diagnosed untreated mild‐to‐moderate hypertension (19 men, 13 women; mean±SD age 51±15 years; diastolic blood pressure 99±12mmHg; systolic blood pressur. 153.2±18.0 mmHg; plasma creatinine 86±15 μmol/L; creatinine clearance 92.2±20.5 mL/min; left ventricular mass index 116±28 g/m2; left ventricular ejection fraction 66±9%). A 15 mL peripheral venous blood sample was obtained at the time of echocardiography for radioimmunoassay of BNP.

3. Sixteen patients had abnormal Doppler transmitral flow (E/A rati. < 1) and a higher median plasma BNP concentration compared with those patients with E/A ≥1 (12.9 vs 5.9 pmol/L, respectively; P = 0.006). The plasma BNP level correlated significantly with E/A ratio (r = ‐0.50; P = 0.035). Multivariate analysis showed that the E/A ratio is related to plasma BNP, independent of age and blood pressure.

4. Our results suggest that the plasma BNP level is influenced by diastolic dysfunction. Further studies are needed to determine whether assay of plasma BNP helps to identify patients with diastolic dysfunction.
ROLE OF LIPOPROTEIN‐X IN FOAM CELL FORMATION AND RAT MESANGIAL CELL PROLIFERATION
Authors: Lynn Edward G. , O Karmin
Published: June 2007

1. In the present study, the effect of reconstituted lipoprotein‐X (rLp‐X) on lipid accumulation and foam cell formation in rat peritoneal macrophages was evaluated. Furthermore, the combined effect of rLp‐X and macrophages on mesangial cell proliferation was examined.

2. Incubation of macrophages with rLp‐X (177 and 387nmol unesterified cholesterol (FC)/mL) resulted in an increase of cellular cholestero. (162%) and cholesteryl esters (223 to 245%) relative to control.

3. Oil Red O staining of macrophages treated with rLp‐X revealed the presence of foa. cells.

4. In conclusion, rLp‐X had no effect on the proliferation of mesangial cells incubated in macrophage‐conditione. medium.
ENDOTHELIAL DYSFUNCTION EXACERBATES THE IMPAIRMENT OF RELAXATION BY LYSOPHOSPHATIDYLCHOLINE IN PORCINE CORONARY ARTERY
Authors: Leung Susan WS , Teoh Hwee , Quan Adrian , Man Ricky YK
Published: June 2007

1. Current evidence suggests that lysophosphatidylcholine (LPC), a component found in oxidized low‐density lipoprotein (Ox‐LDL), inhibits endothelium‐dependent relaxation (EDR) mediated by endothelium‐derived relaxing factor (EDRF) and endothelium‐derived hyperpolarizing factor (EDHF). An objective of the present study was to characterize the roles of the different elements of EDR in LPC‐induced impairment within the porcine coronary artery. Concomitantly, we sought to determine whether impairment of one component of EDR would increase the sensitivity of the endothelium to LPC.

2. Bradykini. (0.1 nmol/L‐0.3 μmol/L) relaxed U46619 (30 nmol/L)‐precontracted porcine coronary artery rings in a concentration‐dependent manner. A reduction in the bradykinin‐elicited response was observed in NG‐nitro‐L‐arginine methyl ester (L‐NAME; 300 μmol/L)‐ and ouabain (50 μmol/L)‐treated rings. Pretreatment with LPC (20 μmol/L), which on its own had no effect on normal endothelial relaxation, resulted in further inhibition of EDRF‐ and EDHF‐induced relaxations.

3. Our results demonstrate that EDRF and EDHF are the primary mediators of EDR in the porcine coronary artery. Our data also show that while a low concentration of LPC (20 μmol/L) does not impair EDR, it can evoke vascular dysfunction following blockade of either the effects of EDRF or EDHF. Therefore, these data suggest that the partially damaged vascular endothelium could be more sensitive to threshold levels of this atherogenic phospholipid.
EPIDEMIOLOGY OF CARDIOVASCULAR RISK FACTORS IN HONG KONG
Authors: Janus ED ,   for the Hong Kong Cardiovascular Risk Factor Prevalence Study Group
Published: June 2007

1. To facilitate the development of appropriate population‐wide coronary heart disease prevention strategies and to monitor their long‐term impact, a comprehensive baseline Hong Kong Cardiovascular Risk Factor Prevalence Study was conducted in 1995–96.

2. The data obtained from 2875 men and women aged 25–74 years showed a high prevalence of diabetes mellitus and impaired glucose tolerance, particularly in those aged 65 years and over. Other risk factors, such as hypercholesterolemia and hypertension as well as being overweight, were particularly prominent in older women.
MYOCARDITIS AS SYSTEMIC DISEASE: NEW PERSPECTIVES ON PATHOGENESIS
Authors: Carthy Christopher M. , Yang Decheng , Anderson Daniel R. , Wilson Janet E. , McManus Bruce M.
Published: June 2007

1. Myocarditis may be an early indicator of or may subsequently lead to dilated cardiomyopathy in humans. This hypothesis has evolved from research on viruses that induce myocarditis, wherein the coxsackie B group viruses (CVB) in the family Picornaviridae are the most common known viral infectants of heart muscle.

2. Many competing hypotheses exist as to the pathogenesis of CVB3‐induced myocarditis, including direct virus‐induced myocyte damage and immunopathological disease with autoimmune sequelae. Evidence to support the direct‐damage and viral RNA‐persistence hypothesis is derived from in situ hybridization and gene amplification studies.

3. Recent use of terminal deoxynucleotidyl transferase‐mediated nick‐end labelling indicates that this injury in target organs is largely non‐apoptotic in nature. Most apoptotic bodies in cardiac tissue are derived from immune cells.

4. Beyond infection of heart muscle, CVB3 can also associate with, infect and persist in cells of immune origin. The CVB3 localizes to follicles in spleens and lymph nodes of the murine host and this particular localization may continue in mice susceptible to more aggressive myocarditis. Whether virus‐immune cell association in these compartments is advantageous (or essential) to the host in the evolution of anti‐viral immune responses or whether it is more advantageous to the virus in immunosuppression of the host is not known.

5. We suggest that CVB3 can directly perturb or alter the immune response, thereby delaying viral clearance from vulnerable systemic organs. Both host and viral genetic factors can influence susceptibility, persistance and disease progression.

6. Picornaviruses use a unique method for the initiation of translation, involving the internal binding of the ribosome on a sequence element of the 5′ untranslated region, termed an internal ribosome entry sit. (IRES).

7. The IRES of CVB3 is located at approximately stem loops G, H and I, spanning nucloetides 530 and 630. Arrest of host translation is also a feature of picornavirus infection. Such regulation of host cell translation machinery no doubt fosters viral replication at the expense of the host cell.

8. Differences between cell types in the mechanisms, along with those at other key steps in the viral life cycle and in signalling via kinase pathways, may determine viral tropism and cellular destruction and the physiological outcome of neighbourin. cells.
POSSIBLE MECHANISM FOR THE ANTI‐ATHEROSCLEROTIC ACTION OF THE CALCIUM CHANNEL BLOCKER AE0047 IN CHOLESTEROL‐FED RABBITS
Authors: Hayashi Kazutaka , Imada Teruaki , Yamauchi Takeshi , Kido Hideaki , Shinyama Hiroshi , Matzno Sumio , Nakamura Norifumi , Kagitani Yoshio
Published: June 2007

1. The present study was designed to investigate the anti‐atherosclerotic effect of AE0047, a calcium channel blocker, and to compare it with that of nilvadipine in cholesterol‐fed rabbits. Furthermore, the effects of AE0047 on low‐density lipoprotein (LDL) oxidation were studiedin vitro.

2. A 7 week treatment period with AE0047 (3 and 10 mg/kg, p.o.) led to a dose‐dependent reduction in the lipid deposition area by Oil Red‐O staining (surface index) without affecting serum lipid levels. There was no reduction in the surface index following treatment with the same dose of nilvadipine (10 mg/kg).

3. In a vehicle‐administered high‐fat diet group of rabbits, levels of total cholesterol (TC) and esterified cholesterol (EC) and calcium content in the aorta were increased approximately two‐ to three‐fold over those of the normal diet group. Increased levels of TC and EC and calcium content were reduced to the same levels as the normal diet group by AE0047 treatment, whereas nilvadipine did not affect TC and EC levels.

4. In anin vitrostudy, AE0047 (10 μol/L) inhibited LDL oxidation and the aggregation of apolipoprotein (Apo) B‐100 induced by Cu2+. Furthermore, AE0047 inhibited the degradation of oxidized LDL by macrophages. In contrast, the same dose of nilvadipine (10 μol/L) did not inhibit either LDL oxidation or the aggregation of ApoB‐100.

5. In summary, AE0047 inhibited LDL oxidation, resulting in a decrease of its uptake into macrophages and an inhibition of cholesterol esterification. This leads to an anti‐atherosclerotic effect of AE0047. Thus, AE0047 may have therapeutic potential in preventing cardiovascular disease in hypertensive patients.
OCCLUSION OF THE ADRENAL VEIN LEADS TO AN INCREASE IN RENAL VASCULAR RESISTANCE IN THE IPSILATERAL KIDNEY
Authors: Abramczyk Piotr , Ziȩcina Rafal , Lisiecka Aurora , Przybylski Jacek
Published: June 2007

1. The aim of the present study was to investigate the effect of an acute increase in blood flow through the adrenal‐renal vascular connection (ARVC), due to occlusion of the adrenal vein, on renal blood flow (RBF) and renal vascular resistance (RVR).

2. Experiments were performed in Wistar‐Kyoto rats. Animals were divided into four groups. In the first group, the adrenal vein was clamped using a metal clip. In the second group, the tissue between the adrenal gland and the kidney was cut before clamping. In the third and fourth groups, α‐adrenoceptor blockade was induced by intravenous infusion of phentolamine before clamping the adrenal vein. In addition, in the fourth group, tissue between the adrenal gland and the kidney was cut before clamping.

3. In the first group, occlusion of the adrenal vein caused an increase in RVR, followed by a decrease in RBF. In the second, third and fourth groups, the same procedure did not change either RBF or RVR.

4. We conclude that the augmented inflow of catecholamines to the kidney through the ARVC changes the haemodynamics of the kidney and may contribute to development of arterial hypertension due to occlusion of the adrenal vein.
RECYCLING OF ACETYLCHOLINE FOLLOWING IMPULSE TRANSMISSION IN RAT MUSCLE REVEALED IN THE PRESENCE OF NEOSTIGMINE
Authors: Uramoto I. , Miyamoto K. , Watanabe K. , Totsuka T.
Published: June 2007

1. The recycling process of acetylcholine (ACh) following impulse transmission was studied in terms of muscle potentials evoked by repetitive stimulation in the presence of neostigmine.

2. Wistar rats were anaesthetized with urethane and muscle potentials were recorded with concentric electrodes from their exposed medial gastrocnemius muscles before and after the injection of neostigmine.

3. All potentials before neostigmine treatment were similar in amplitude. A set of 10 stimuli was given at 0.5 Hz 6–8 min after drug administration. The first potential was as large as that before it. The second potential was greatly depressed. Thereafter, potentials gradually recovered.

4. Two sets of 10 stimuli were delivered at a 1 min interval (i.e. with a 40 s rest period between them). The second potential was not depressed so severely in the second set as in the first set. The same procedure was repeated in some rats and the aforementioned phenomenon was noted. When two sets of 10 stimuli were given at an interval of 2 min or more, the second potential was equally depressed in the both sets of stimuli.

5. The recycling of ACh following impulse transmission in the junctional region was revealed in terms of muscle potentials in the presence of neostigmine. This process was activated due to repetitive stimulation. Moreover, the activated state seemed to be maintained for a while after the cessation of stimuli. These results suggest the possible existence of a neural mechanism that can exert an influence on the recycling of ACh following impulse transmission beyond a short period of time.
FUNCTIONAL DIVERSITY OF INFILTRATING MACROPHAGES IN INFLAMED HUMAN COLONIC MUCOSA ULCERATIVE COLITIS
Authors: Oshitani Nobuhide , Kitano Atsuo , Kakazu Tomomasa , Hara Junichi , Adachi Kenji , Nakamura Shiro , Matsumoto Takayuki , Kobayashi Kenzo
Published: June 2007

1. Phenotypical heterogeneity of macrophages infiltrating the colonic mucosa of patients with ulcerative colitis has been shown in many reports. The functional diversity of macrophages in inflamed colonic mucosa remains unclear.

2. Intestinal macrophages have been characterized by immunohistochemical staining and their ability to generate free oxygen radicals in inflamed and non‐inflamed mucosa.

3. No correlation was found between RFD1 (activated dendritic cells), RFD7 (tissue macrophages) or RFD9 (epithelioid cells, giant cells in association with granuloma) positivity and either CD68 or human histocompatibility complex class II antigen (HLA‐DR) positivity. The proportions of RFD7‐ and RFD9‐positive cells were significantly increased in inflamed colonic mucosa. Nitroblue tetrazolium‐reducing mononuclear cells were CD68 or RFD7 positive but they were rarely positive for HLA‐DR and RFD1.

4. These results suggest that nitroblue tetrazolium‐reducing macrophages are (scavenger) macrophages.
HUMAN RESPIRATORY MUSCLES: SENSATIONS, REFLEXES AND FATIGUABILITY
Authors: Gandevia SC , Allen GM , Butler JE , Gorman RB , McKenzie DK
Published: June 2007

1. Given the importance of the ventilatory ‘pump’ muscles, it would not be surprising if they were endowed with both sensory and motor specializations. The present review focuses on some unexpected properties of the respiratory muscle system in human subjects.

2. Although changes in blood gas tension were long held not to influence sensation directly, studies in subjects who are completely paralysed show that increases in arterial CO2 levels elicit strong sensations of respiratory discomfort.

3. Stretch reflexes in human limb muscles contain a monosynaptic spinal excitation and a long‐latency excitation. However, inspiratory muscles show an initial inhibition when tested with brief airway occlusions during inspiration. This inhibition does not depend critically on input from pulmonary or upper airway receptors.

4. Human inspiratory muscles (including the diaphragm) have been considered to fatigue during inspiratory resistive loading. However, recent studies using phrenic nerve stimulation to test the force produced by the diaphragm show that carbon dioxide retention (hypoventilation) and voluntary cessation of loading occur before the muscles become overtly fatigued.
INCREASED LEVELS OF ENDOTHELIN ETB RECEPTOR mRNA IN HUMAN OMENTAL ARTERIES AFTER ORGAN CULTURE: QUANTIFICATION BY COMPETITIVE REVERSE TRANSCRIPTION‐POLYMERASE CHAIN REACTION
Authors: Möller Sebastian , Adner Mikael , Edvinsson Lars
Published: June 2007

1. Using competitive reverse transcription‐poly merase chain reaction (RT‐PCR) and in vitro pharmacology, smooth muscle endothelin ETb receptor expression was studied in segments of human omental artery, fresh and after organ culture for 1 and 5 days.

2. The competitive RT‐PCR assay used in the present study uses an internal RNA standard bearing a 69 b.p. deletion in order to control all steps of the reaction, including the RT step. Control experiments showed linearity overlive subsequent 1:10 dilutions and a wide range of cycle numbers. The assay was able to quantify subattomolar concentrations in samples under 1 μg total RNA, making it possible to measure mRNA expression even in small tissue biopsies.

3. In fresh arteries, ETb mRNA levels were 0.19±0.05 amol/μg total RNA (range 0.03–0.42 amol/μg; n= 8). After organ culture, an increase in ETB mRNA levels by 317 ± 28 and 288 ± 12% was found at days 1 and 5, compared with fresh arteries, respectively.

4. In vitro pharmacology showed that endothelin (ET)‐l induced a strong and potent contraction in fresh arteries, whereas the selective ETB receptor agonist IRL1620 failed to induce a significant contraction. The ET‐1‐induced contraction was not altered in potency or Emax after organ culture for 1 and 5 days. In contrast, IRL 1620 induced a clear contraction after 1 day, which increased further in both Emax and potency after 5 days organ culture.

5. Our results indicate that a massive new transcription of ETb receptor mRNA is induced by organ culture, resulting in functional contractile ETb receptors on the smooth muscle layer.
EFFECTS OF PROSTAGLANDIN E2 ON RENAL FUNCTION AND LUNG LIQUID DYNAMICS IN FOETAL SHEEP
Authors: Wlodek ME , Hooper SB , Thorburn GD , Tester ML , Harding R.
Published: June 2007

1. The aim of the present study was to determine the effects of prolonged prostaglandin E2 (PGE2) administration on the function of the foetal kidneys and lungs in order to gain a greater understanding of the role played by PGE2 in the control of foetal fluid balance. By studying the effects of PGE2 at two gestational ages, we have also been able to examine the influence of age.

2. We studied the effects of 26 h PGE2 infusion on foetal sheep at a mean (±SEM) of 120.0 ± 0.6 (n= 6) and 139.0 ± 0.8 (n= 4) days of gestation. In both groups, foetal urine production was significantly inhibited throughout the infusion period (P < 0.05). In younger, but not older foetuses, urine production returned to control values within 24 h of ending the infusion (P < 0.05). This PGE2‐induced anti‐diuresis was associated with foetal hypoxaemia and acidaemia, a reduction in free water clearance and an increase in foetal plasma arginine vasopressin concentrations (P < 0.05).

3. During PGE2 infusions, foetal breathing movements were inhibited, the effect being greater and more sustained in older foetuses (P < 0.05).

4. Infusions of PGE2 led to increased lung liquid production at both ages (P < 0.05); lung liquid volumes were reduced in older foetuses (P < 0.05), but were unchanged in younger foetuses. The reduction in lung liquid volume in older foetuses may have been due to inhibition of foetal breathing.

5. We conclude that increased circulating levels of PGE2 have profound effects on foetal renal and lung function which, if sustained, could compromise foetal lung development and perinatal well‐being.
EFFECT AND MECHANISM OF CARDIOPLEGIC ARREST ON THE CORONARY ENDOTHELIUM‐SMOOTH MUSCLE INTERACTION
Authors: He Guo‐Wei
Published: June 2007

1. During cardiac 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 and morbidity.

2. We investigated coronary endothelium‐smooth muscle interaction after exposure to depolarizing (hyperkalaemic; K+ 20 or 50 mmol/L) and hyperpolarizing (the K+ channel opener aprikalim) cardioplegia and organ preservation solution (University of Wisconsin (UW) solution). Endothelium‐dependent relaxation and hyperpolarization of the coronary smooth muscle were studied in the porcine and human large conductance and micro‐coronary arteries. Intracellular free calcium concentration in endothelial cells was also measured.

3. The endothelium‐derived hyperpolarizing factor (EDHF)‐mediated relaxation to A23187, bradykinin, and substance Pin arteries contracted by either U46619 (10nmol/L) or K+ (25 mmol/L) was reduced after exposure to either high K+ or UW solution, but was maximally preserved after exposure to aprikalim. The hyperpolarization of the membrane potential in response to the above endothelium‐derived relaxing factor stimuli was also reduced by exposure to depolarizing cardioplegia. Studies in microcoronary arteries are in accordance with findings in large arteries. The intracellular free calcium concentration remained unchanged after exposure to hyperkalaemia.

4. We concluded that: (i) during cardiac surgery, the function of coronary circulation may be changed due to exposure to depolarizing cardioplegia or preservation solutions; (ii) the functional change in the coronary circulation is related to the altered interaction between the endothelium and smooth muscle; (iii) depolarizing (hyperkalaemia) cardioplegia or hyperkalaemic organ preservation solutions affect endothelium‐smooth muscle interaction through the EDHF pathway; (iv) EDHF relaxes the porcine large and microcoronary arteries through multiple K+ channels; and (v) that hyperpolarizing vasodilators (K+ channel openers) may protect EDHF‐mediated endothelial function when used as cardioplegia.
ENDOTHELIUM‐SMOOTH MUSCLE INTERACTION IN CARDIAC TRANSPLANTATION
Authors: Skarsgard Peter L. , McManus Bruce M. , van Breemen Casey , Laher Ismail
Published: June 2007

1. The inducible isoform of nitric oxide synthase (iNOS) is expressed in human and experimental cardiac allografts and is localized to infiltrating macrophages, cardiac myocytes, endothelial cells and smooth muscle cells. A recent clinical report proposes a causal link between myocardial expression of iNOS and ventricular contractile dysfunction, a potentially graft‐ and life‐threatening post‐transplant complication.

2. Coronary blood flow is elevated in human graft recipients with biopsy proven cellular rejection, indicating that vasodilation accompanies graft rejection. In Lewis‐to‐F‐344 coronary resistance vessels, which show intimal expression of iNOS, pressure‐induced myogenic tone is significantly inhibited. Selective iNOS inhibition partially reverses the inhibition of myogenic tone, confirming that iNOS produces vasoactive nitric oxide (NO) and may mediate the rejection‐induced vasodilation seen clinically.

3. Endothelial dysfunction, identified as loss of endothelium‐dependent dilation, has tremendous prognostic significance in vascular diseases of multiple aetiologies. In transplantation, endothelial dysfunction predicts early cardiac allograft vas‐culopathy and poor clinical outcome. Lewis‐to‐F‐344 coronary vessels develop endothelial dysfunction at 1 week post‐transplantation, but this is preceded by a transient state of endothelial cell hyperfunction, with enhanced endothelial production of NO.

4. The normal interaction between endothelial and smooth muscle cells in coronary resistance vessels is critical for the regulation of coronary blood flow and the maintenance of fluid homeostasis. With allospecific expression of iNOS, the inhibition of vascular tone predicts greatly enhanced intravascular pressure in precapillary arterioles and capillaries; this would be expected to cause a net movement of fluid from the intravascular compartment into the myocardial interstitium, resulting in ventricular oedema, non‐compliance and poor contractile performance.
SECOND‐, MINUTE‐ AND HOUR‐METRONOMES OF INTESTINAL PACEMAKERS
Authors: Bywater Robert AR , Spencer Nick J. , Fida Rose , Taylor Grahame S.
Published: June 2007

1. Movements of the gastrointestinal tract are required for the digestion of food and the expulsion of waste products.

2. The present paper will discuss the nature of electrical rhythms underlying some intestinal motility patterns.

3. The rhythms are generated by pacemakers with cycle rates appropriate to controlling individual contractions, motor pat‐ternings or switching between different motor programmes.

4. Electrical rhythms are discussed with periods of the order of seconds, minutes and hours.

5. Particular discussion is centred on rhythms recorded from the small and large intestine of the mouse.
GENERATION AND ENTRAINMENT OF ORCADIAN RHYTHMS
Authors: Kennaway David J.
Published: June 2007

1. The present brief review examines some of the new developments in the area of circadian rhythm research.

2. The discovery of the mouse clock and m‐per genes and their similarity to other clock genes like per and tint has provided new insight into the control of rhythms in vertebrates. In mice, these genes are expressed in the site of the biological clock, the suprachiasmatic nucleus (SCN), and so will now become a focus of research into the generation of rhythmicity.

3. Because SCN cells expressing endogenous rhythms have a periodicity different from 24 h, there must be mechanisms in place to reset the rhythms on a daily basis. This is achieved in mammals by retinal light perception and neural transmission through several discrete pathways to the SCN.

4. The nature of the neurotransmitters involved in this transfer of environmental information to the timing system is controversial and may even vary between similar species but, in the rat, there is compelling evidence that a serotonergic pathway is pre‐eminent in mediating the effects of light. How the re‐setting is achieved at the cellular level is not known.
RENAL DISEASE AS A METAPHOR: TOWARDS A MORE INTEGRATED VIEW OF ABORIGINAL HEALTH
Authors: Hoy Wendy E.
Published: June 2007

1. The health of Aboriginal people in the Northern Territory of Australia is among the worst in the world, with mortality rates increased in every ‘disease‐specific’ category and averaging overall approximately five‐fold those of non‐Aboriginal Australians. Health services, which in most regions are rudimentary, fragmented and underresourced, have been slow to recognize and meet this challenge. However, the cost implications of an epidemic of renal failure have stimulated concern that broader mortality statistics could not.

2. In one high‐risk Aboriginal community, we found that renal disease can be detected and its course chartered by a simple and reliable screening test. Renal disease arises out of a broad menu of risk factors that reflect poverty, disadvantage and accelerated lifestyle changes and its expression is progressively amplified with the simultaneous operation of more than one risk factor. It is intimately related to other ‘diseases’ through shared risk factors and pathophysiology. We also found that people with established renal disease participated enthusiastically in a pharmacological treatment programme, with excellent clinical responses that predict a marked reduction in renal failure and cardiovascular morbidity and mortality over the intermediate term.

3. It is likely that most other causes of excess mortality in Aboriginal people are, like renal disease, multideterminant, with a substantial base of shared risk factors. They are probably equally susceptible to modification. We must move away from ‘single‐cause’ disease models, eliminate counterproductive specialty barriers and rectify the unbalanced focus and resource commitment to hospital‐based, high technology treatments of people with advanced and irreversible disease. We must advocate for coherent, sustained, integrated public health and primary care programmes to improve the whole health profile and for screening and treatment programmes to modify the course of disease in people already afflicted.
PHYSIOLOGICAL EVIDENCE FOR ARTERIOVENOUS ANASTOMOSES IN THE UTERINE CIRCULATION OF LATE‐PREGNANT EWES
Authors: Miller Suzanne L. , Dickson Kerry , Jenkin Graham , Walker David W.
Published: June 2007

1. The objective of the present study was to determine whether arteriovenous anastomoses (AVA) are present in the uterine circulation of conscious, late‐pregnant ewes.

2. Twenty late‐pregnant ewes were assigned to two groups. In group 1, 15 μm coloured microspheres were injected into the uterine artery of the pregnant horn and the relative proportion of microspheres trapped in the uterus and lungs was determined. The percentage shunting of blood measured by this method was 17 ± 3%, representing a blood flow of 164 ± 39 mL/min (n= 12). Any contribution of ovarian, cervical, rectal and other vascular beds was specifically excluded in this group.

3. In group 2, total uterine capillary flow was measured using the reference blood flow method, by injecting 15 μm microspheres into the heart. Calibrated flow probes, placed on both main uterine arteries, concurrently measured total uterine blood flow. Total blood flow to the uterus (flow probe) was significantly greater (t= 3.415; P= 0.027) than uterine capillary flow (microspheres), indicating AVA shunting in the uterine circulation. Mean total blood flow to the uterus was 1749 ± 160 mL/min, of which an average 25 ± 5% (n = 5 sheep) was shunted.

4. The percentage AVA shunting for groups 1 and 2 was not significantly different (t= 1.219; P= 0.24) and, when combined, the mean percentage of uterine blood flow passing through AVA in the late‐pregnant sheep was determined to be 19 ± 23%.

5. The present study shows that AVA are present and patent in the uterine circulation of late‐pregnant ewes and that they account for the shunting of approximately 20% of the uterine blood flow into the maternal venous circulation.
TRILINOLEIN INHIBITS THE ADHESION OF NEUTROPHILS TO ENDOTHELIAL CELLS
Authors: Hang CY , Huang SS , Wang R. , Sung YJ , Kwok CF
Published: June 2007

1. Trilinolein is a triacylglycerol with linoleic acid as the only type of fatty acid in all three esterified positions of glycerol. It was recently reported to have a myocardial protective effect in coronary ligated rats. We now study its effect on the adhesion of human neutrophils to cultured bovine endothelial cells.

2. Pretreatment of an endothelial monolayer with trilinolein at concentrations ranging from 10‐10 to 10‐6 mol/L significantly inhibited neutrophil adhesion to endothelial cells. Trilinolein was less potent than sodium nitroprusside in inhibiting neutrophil adhesion.

3. The inhibitory effect of trilinolein was antagonized by methylene blue and NG‐nitro‐L‐arginine methyl ester. The inhibitory effect of trilinolein was not mediated through linoleic acid because linoleic acid did not inhibit neutrophil adhesion.

4. Pretreatment of neutrophils with trilinolein did not reduce neutrophil adhesion. However, in neutrophils activated with N‐formyl‐methionyl‐leucyl‐phenylalanine, trilinolein inhibited the neutrophil adhesion to endothelial cells.

5. We conclude that trilinolein inhibits neutrophil adhesion to the endothelial monolayer by stimulating the nitric oxide and cyclic GMP pathways in endothelial cells. It may also inhibit neutrophil adhesion by scavenging free radicals. The inhibitory effect of trilinolein on neutrophil adhesion may play a role in its myocardial protective activity.