bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF LOSARTAN ON THE CARDIOVASCULAR SYSTEM, RENAL HAEMODYNAMICS AND FUNCTION AND LUNG LIQUID FLOW IN FETAL SHEEP
Authors: Stevenson Kathleen M. , Gibson Karen J. , Lumbers Eugenie R. 
Published: June 2007

SUMMARY1. The angiotensin type 1 (AT1) receptor antagonist, losartan (10 mg/kg) was infused intravenously into nine chronically catheterized fetal sheep (125–132 days gestation). Losartan reduced the fetal systolic (P < 0.01) and diastolic (P < 0.01) pressor response to 5 μg angiotensin II (AngII) i.v. from 27.4 ± 1.5 to 7.4 ± 0.9 and from 17.5 ± 1.3 to 5.4 ± 0.6 mmHg, respectively, after 1h and to 6.1 ± 0.5 and 4.4 ± 0.5 mmHg, respectively, after 2h. Maternal pressor responses to 5 μg AngII i.v. were unchanged. Fetal mean arterial pressure decreased (P < 0.05) after losartan administration, but fetal heart rate did not change.2. Fetal haematocrit increased (P < 0.05), fetal PO2 decreased (P < 0.01), PCO2 did not change and pH decreased (P < 0.01), as did plasma bicarbonate levels (P < 0.01) following administration of losartan. Thus, losartan induced a fetal metabolic acidosis.3. Fetal placental blood flow did not change following administration of losartan. In the fetal kidney, losartan caused a decrease in vascular resistance (P < 0.01) and an increase in blood flow (P < 0.05). Glomerular filtration rate decreased (P < 0.05); thus, filtration fraction decreased (P < 0.01). There was no change in the fractional reabsorption of sodium and glomerulotubular balance was maintained. Free water clearance decreased (P < 0.01) and became negative. Urine flow decreased (P < 0.01), the excretion rates of sodium, potassium and chloride did not change, but the urinary sodium:potassium ratio decreased (P < 0.05). There was a decrease in lung liquid flow (P < 0.05) following losartan.4. It is concluded that the fetal renin‐angiotensin system (RAS) is important in the maintenance of fetal arterial pressure, the regulation of fetal renal blood flow and is essential in the maintenance of fetal glomerular function. Further, these actions of AngII are mediated via functional AT1 receptors. These effects of losartan on the fetal cardiovascular system, renal blood flow and function are similar to those observed following captopril administration. Thus, the effects of angiotensin converting enzyme (ACE) inhibition in the foetus are due to the blockade of the fetal RAS and are independent of any direct effects on bradykinin or prostaglandin levels.
REGULATION AND INTERACTIONS OF TRANSFORMING GROWTH FACTOR‐β WITH CARDIOVASCULAR CELLS: IMPLICATIONS FOR DEVELOPMENT AND DISEASE
Authors: Saltis John , Agrotis Alex , Bobik Alex 
Published: June 2007

SUMMARY1. Transforming growth factors‐β (TGF‐β) are multifunctional proteins that regulate cell growth, differentiation, migration and extracellular matrix production and have an important role in embryonic development and tissue remodelling.2. The diverse biological actions of TGF‐β are elicited following their interaction with type I and type II TGF‐β receptors, both of which are transmembrane serine/threonine kinases, suggesting an important role for protein phosphorylation in the mechanism of action of these cytokines on the growth of cells and their extracellular environment.3. Alterations in TGF‐β gene expression and action in various cell types associated with the cardiovascular system may contribute to the pathophysiology of a number of diseases, such as hypertension, atherosclerosis and restenosis, as well as the development of cardiac abnormalities.
EFFECTS OF DC‐015, A NOVEL POTENT AND SELECTIVE α1‐ADRENOCEPTOR ANTAGONIST ON PLASMA LIPID AND VASCULAR REACTIVITY IN HYPERLIPIDAEMIC RATS
Authors: Sheu Joen‐Rong , Peng I‐Hsun , Lee Yen‐Mei , Yen Mao‐Hsiung 
Published: June 2007

SUMMARY1. The effects of DC‐015, a newly synthesized quinazoline derivative, on plasma lipids, lipoprotein levels and vascular reactivity were investigated in Wistar‐Kyoto rats (WKY) and spontaneously hypertensive rats (SHR).2. The hypotensive effect of DC‐015 was compared with prazosin in SHR. Intravenous administration of DC‐015 and prazosin (both at 0.01, 0.05 and 0.1mg/kg) induced dose‐dependent reductions in mean arterial pressure (MAP) which reached a maximal effect 5 min after injection and persisted over 2 h in SHR. DC‐015 decreased MAP with equal efficiency compared with prazosin.3. The plasma levels of total cholesterol (CE), low‐density lipoprotein (LDL)‐CE and total triglyceride (TG) were markedly increased and the levels of high‐density lipoprotein (HDL)‐CE were markedly decreased in both high fat‐high cholesterol (HF‐HC) diet fed WKY and SHR.4. In HF‐HC diet fed WKY and SHR, the total plasma CE, LDL‐CE and total plasma TG were significantly reduced after oral administration of DC‐015 (1 mg/kg, twice a day) for 4 weeks. Furthermore, DC‐015 therapy was associated with increased HDL‐CE levels and thus the ratio of total CE to HDL‐CE was improved. The antihyperlipidaemic effect of prazosin was less than that of DC‐015.5. Significantly attenuated median effective concentration (EC50) values and augmented maximal responses for phenyl‐ephrine‐induced contraction of aortic rings were observed in HF‐HC diet fed WKY and SHR. Endothelium‐dependent relaxation to acetylcholine was impaired while endothelium‐independent relaxation to nitroglycerin was well preserved.6. Oral administration of DC‐015 (1 mg/kg, twice a day) for 4 weeks significantly augmented EC50 values and attenuated maximal responses for phenylephrine‐induced contraction of aortic rings in HF‐HC diet fed WKY and SHR. Prazosin (1 mg/kg, twice a day) showed a lesser extent of efficiency than DC‐015 at normalization of vasorelaxation in HF‐HC diet fed WKY and SHR.7. It is concluded that DC‐015, a potent antihypertensive agent, may have additional advantage in also reducing hyperlipidaemia.
EFFECT OF THE HYDROXYL RADICAL ON FIBROBLAST‐MEDIATED COLLAGEN REMODELLING IN VITRO
Authors: Arisawa Shoko , Arisawa Tomiyasu , Ohashi Masaru , Nitta Yukiko , Ikeya Toshihiko , Asai Junpei 
Published: June 2007

SUMMARY1. It has been reported that free radicals prevent wound healing. However, the mechanism of this effect is not yet clear. We attempted to clarify the influence of hydroxyl radicals on wound healing in vitro.2. We used an ascorbate‐copper ion system (ACS) to produce hydroxyl radicals in accordance with variables of time elapsed and concentration of copper ion. The effects of hydroxyl radical on fibroblast‐mediated collagen remodelling, cell viability, the functions of fibroblasts and collagen fibrils were studied.3. With a copper ion concentration of 100μmol/L ACS significantly reduced contraction, while 10μmol/L stimulated contraction. Hydrogen peroxide (H2O2) was employed in observing these findings. ACS did not influence cell viability, the expression of α2β1 integrin and cellular fibronectin, or the cytoskeletal organization of fibroblasts involving actin until 3h. A concentration of ACS at 10μmol/L of copper ion induced the polymerization of collagen after 30 min, while ACS at 100 μmol/L induced collagen degradation; this finding was also established by using H2O2. Collagen reduced the amount of formaldehyde produced by trapping hydroxyl radical with dimethyl sulfoxide.4. Our findings suggest that collagen is denatured by scavenging the hydroxyl radical before fibroblasts are damaged, so that the radical may influence the remodelling of collagen.
PROTECTIVE EFFECTS OF ME3221 ON HYPERTENSIVE COMPLICATIONS AND LIFESPAN IN SALT‐LOADED STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Nagura Jun , Yamamoto Mikio , Hui Chen , Yasuda Sumie , Hachisu Mitsugu , Konno Fukio 
Published: June 2007

SUMMARY1. A comparison was made on the protective effects of the following: ME3221, a competitive angiotensin AT1 receptor antagonist; losartan, in which a major active metabolite is a non‐competitive angiotensin AT1 receptor antagonist; and enalapril, an angiotensin‐converting enzyme inhibitor, using the salt‐loaded stroke‐prone spontaneously hypertensive rats (SHRSP).2. SHRSP received orally ME3221 (3 and 10mg/kg per day), losartan (10mg/kg per day) and enalapril (10mg/kg per day) from the 6th to the 20th week of age. All the control rats showed rapid elevation of systolic blood pressure (SBP), accompanied by hypertensive complications, and died by 15 weeks of age.3. ME3221, losartan and enalapril suppressed the elevation of SBP in the salt‐loaded SHRSP to a comparable degree. ME3221 and losartan increased the survival rate to >90%, and diminished hypertensive complications such as cerebral apoplexy (stroke), renal injury (increased proteinuria, and total N‐acetyl‐β‐D‐glucosaminidase activity) and heart failure (cardiac hypertrophy and pleural effusion).4. Competitive (ME3221) and non‐competitive (losartan) angiotensin AT1 receptor antagonists showed comparable efficacy against the complications and mortality of the salt‐loaded SHRSP; both were more potent than enalapril in the protective effect.
SUPPRESSIVE EFFECTS OF A HERBAL FORMULA, TBL‐1, ON TYPE II COLLAGEN‐INDUCED ARTHRITIS IN DBA/1J MICE
Authors: Li Song‐Hua , Kobayashi Yuta , Yamauchi Yasutaka , Gonda Tatsuo , Tsunematsu Tokugoro 
Published: June 2007

SUMMARY1. The effects of a formula of traditional Chinese medicine, TBL‐1, on collagen‐induced arthritis (CIA) were investigated in DBA/1J mice.2. From 4 weeks after the first immunization with bovine type II collagen (CII), TBL‐1 or indomethacin was administered orally for 13 weeks.3. Clinical scores of CIA were decreased by both TBL‐1 and indomethacin intervention compared with the control CII‐immunized group.4. Radiographic scores of phalangeal destruction were markedly improved by TBL‐1 intervention (P<0.001), but indomethacin failed.5. The suppressive effects of TBL‐1, but not indomethacin, were manifested in reduced serum anti‐CII antibody titres (P<0.001).6. These findings suggest that TBL‐1 may play a role in regulating some immune responses in the present arthritis model.
REGULATION OF EXPRESSION OF THE ENDOTHELIAL CELL NITRIC OXIDE SYNTHASE
Authors: Harrison David G. , Sayegh Hassan , Ohara Yuichi , Inoue Nobutaka , Venema Richard C. 
Published: June 2007

SUMMARY1. Recent studies have provided insight into how the expression of endothelial cell nitric oxide synthase (ecNOS) is regulated.2. The promoter of ecNOS has several features that are compatible with a constitutively expressed, so‐called ‘house keeping’ gene. These include absence of a TATA box and the presence of Sp1 binding sites located near the transcription start site. The promoter also contains a number of putative binding domains which suggests that it may be regulated by a variety of transcription factor mediated signals.3. Studies of cultured endothelial cells suggest that ecNOS expression is modulated by shear stress, transforming growth factor beta, inhibition of protein kinase C and the state of proliferation. These experiments indicate that although the ecNOS is a ‘constitutively expressed’ gene, its content in the endothelium is subject to modest degrees of regulation that may have important physiological and pathophysiological implications.
VASCULAR REMODELLING AND MOLECULAR BIOLOGY: NEW CONCEPTS AND THERAPEUTIC POSSIBILITIES
Authors: Agrotis Alex , Bobik Alex 
Published: June 2007

SUMMARY1. Over the past decade major advances in molecular cell biology have greatly increased our understanding of the way in which many growth factor genes are expressed and regulated. This knowledge is currently being translated into investigations of the cardiovascular system.2. Two growth factor families appear to play particularly important roles, the fibroblast growth factors and the transforming growth factors‐β. These are multifunctional growth factors capable of remodelling the vasculature through their effects on cell migration, proliferation and matrix formation.3. An understanding of their regulation, properties and nature of their receptors is providing novel insights into the physiology and pathobiology of the vasculature. It is also providing highly specific targets for future therapy.
SODIUM STATUS, CORTICOSTEROID METABOLISM AND BLOOD PRESSURE IN NORMAL HUMAN SUBJECTS AND IN A PATIENT WITH ABNORMAL SALT APPETITE
Authors: Ingram Mary C , Wallace A Michael , Collier Andrew , Fraser Robert , McConnell John 
Published: June 2007

SUMMARY1. A patient with severe hypertension was found to have mildly impaired 11β‐hydroxysteroid dehydrogenase (11β‐HSD) activity on the basis of urinary steroid metabolite ratios, low plasma aldosterone, angiotensin II and renin levels and marginally low levels of plasma potassium.2. The patient also had a compulsively high salt intake.3. We tested the hypothesis that high salt intake may affect 11β‐HSD activity.4. High salt intake in normal subjects did not significantly alter either blood pressure or 11β‐HSD activity.5. We suggest that the potentially small hypertensive effect of the partial enzyme deficiency in our patient, also reported in patients with essential hypertension, has been markedly amplified by the very high salt intake.
RELATIONSHIP OF CIGARETTE SMOKING TO BLOOD PRESSURE AND SERUM LIPIDS AND LIPOPROTEINS IN MEN
Authors: Imamura Hiroyuki , Tanaka Keiko , Hirae Chinatsu , Futagami Tomomi , Yoshimura Yoshitaka , Uchida Kazuhiro , Tanaka Ayumi , Kobata Daikichi 
Published: June 2007

SUMMARY1. The relationship of cigarette smoking to blood pressure and serum lipids and lipoproteins was studied in 7608 men, ranging from 40 to 59 years of age. Analyses were performed separately for non‐drinkers and drinkers.2. After adjusting age and body mass index (BMI) in non‐drinkers and age, BMI and alcohol intake in drinkers in forward stepwise multiple regression analysis, there was a dose‐dependent negative relationship between cigarette smoking and diastolic blood pressure (DBP) and high density lipoprotein cholesterol (HDL‐C), regardless of drinking habit. There was a dose‐dependent positive relationship between cigarette smoking and the ratio of total cholesterol (TC) to HDL‐C (TC:HDL‐C) in non‐drinkers, but not in drinkers. There was a dose‐dependent negative relationship between cigarette smoking and TC and a positive relationship between cigarette smoking and triglycerides (TG) in drinkers, but not in non‐drinkers.3. After matching age and BMI in non‐drinkers, subjects who smoked more than 30 cigarettes/day had significantly lower mean values of systolic blood pressure (SBP; 4.3%; P<0.05), DBP (3.0%;P<0.01) and HDL‐C (15.5%;P<0.01) and higher mean values of TC:HDL‐C (25.0%;P<0.01), TG (46.8%; P<0.01) and β‐lipoprotein (12.0%; P<0.01) than non‐smokers. In drinkers, after matching age, BMI, and alcohol intake, subjects who smoked more than 30 cigarettes/day had significantly lower mean values of SBP (2.8%; P<0.05), DBP (4.8%; P<0.01), HDL‐C (17.3%; P<0.01) and TC (4.4%; P<0.01) and higher mean values of TC:HDL‐C (15.4%; P<0.01) and TG (45.1%;P<0.01) than non‐smokers.4. Although the results are somewhat variable, the present study reveals that cigarette smoking is negatively associated with SBP and DBP and unfavourably associated with lipids and lipoproteins, regardless of drinking habit.
BLOOD PRESSURE LOWERING IN PATIENTS WITH CEREBROVASCULAR DISEASE: RESULTS OF THE PROGRESS (PERINDOPRIL PROTECTION AGAINST RECURRENT STROKE STUDY) PILOT PHASE
Authors: Neal Bruce , Anderson Craig , Chalmers John , MacMahon Stephen , Rodgers Anthony , Committee PROGRESS Management 
Published: June 2007

SUMMARY1. Among patients with cerebrovascular disease, there is a direct and continuous association between blood pressure and the risk of stroke, but previous trials of blood pressure lowering in this patient group have been inconclusive.2. PROGRESS (Perindopril Protection Against Recurrent Stroke Study) is a multicentre, randomized, placebo‐controlled trial that aims to determine reliably the effect of angiotensin converting enzyme (ACE) inhibitor‐based blood pressure lowering on stroke risk in patients with a history of cerebrovascular disease. If a 4 week run‐in period on active perindopril is well tolerated, participants are randomized to either perindopril (4 mg) ± indapamide (2.5 mg) or matching placebo(s). The primary study outcome is stroke and follow‐up is for a minimum of 4 years.3. For the pilot study nearly 5000 medical records were screened and 60 patients with recent cerebrovascular events were approached directly in hospital or at a clinic visit. Sixtyseven patients entered the run‐in phase (52 from retrospective screening and 15 by prospective approach) and 60 patients proceeded to randomization. Treatment with perindopril was well tolerated; only three patients were withdrawn due to side effects and four were withdrawn for other reasons. The mean age of randomized patients was 68 years; 70% were male and 55% were ‘non‐hypertensive'. The mean entry blood pressure was 142/83 mmHg and following pre‐randomization treatment this was reduced by 7/4 mmHg.4. Most patients were identified by retrospective review of medical records, but this was less efficient than prospective methods. Blood pressure lowering was well tolerated by both hypertensive and non‐hypertensive patients with cerebrovascular disease. The small numbers of patients and the nonrandomized nature of the data reported limit the conclusions that can be drawn, but the results confirm the feasibility of the main study.
RECENT INSIGHTS INTO THE REGULATION OF CEREBRAL CIRCULATION
Authors: Brian Johnny E , Faraci Frank M , Heistad Donald D 
Published: June 2007

SUMMARY1. Mechanisms that regulate the cerebral circulation have been intensively investigated in recent years. The role of several vasodilator mechanisms has been examined in the cerebral circulation, including nitric oxide (NO), trigeminal peptides and potassium channels, as well as the potent vasoconstrictor endothelin. These mediators appear to play a role in physiological and pathophysiological responses of the cerebral circulation. In the present review, we will focus on some recent developments in each of these areas.2. Nitric oxide is an important regulator of cerebral vascular tone. Tonic production of NO maintains the cerebral vasculature in a dilated state. NO appears to be an important vasodilator during activation of neurons by excitatory amino acids, somatosensory stimulation and cortical spreading depression. Tonic production of NO appears to be critical in vasodilatation during hypercapnia, although NO may not directly mediate vasodilatation. NO produced by immunological NO‐synthase appears to be important in dilatation following exposure to bacterial endotoxin.3. Calcitonin gene‐related peptide (CGRP), released from trigeminal perivascular sensory nerves in the brain, is an extremely potent dilator of brain vessels. CGRP may limit noradrenaline‐induced constriction of cerebral vessels and contribute to dilatation during hypotension (autoregulation), reactive hyperaemia, seizures and cortical spreading depression.4. Activation of potassium channels leads to hyperpolarization of cerebral vascular smooth muscle and appears to be a major mechanism for dilatation of cerebral arteries. Agents that increase the intracellular concentration of cyclic 3′ 5′‐adenosine monophosphate (cAMP) produce vasodilatation in part by activation of large conductance calcium‐activated potassium channels (BKCa) and ATP‐sensitive potassium channels (KATP). Activation of both KATP and BKCa channels also appears to contribute to vasodilatation during hypoxia. In contrast to KATP channels, BKCa channels appears to be active under basal conditions, contributing to tonic dilatation of cerebral blood vessels.5. Endothelin is produced in the brain, but its role in the physiological regulation of cerebral blood flow is not known. Endothelin may contribute to the spasm of cerebral arteries following subarachnoid haemorrhage.
SPONTANEOUS AND AGONIST‐INDUCED CONTRACTIONS AND ENDOTHELIUM‐DEPENDENT RELAXATION IN AORTAE FROM SHRSP AND WKY RATS UNDER VARIOUS LEVELS OF PASSIVE FORCE
Authors: Sekiguchi Fumiko , Adachi Tomoko , Matsubara Hideki , Matsuda Kyoko , Kita Katsuhiro , Shimamura Keiichi , Sunano Satoru 
Published: June 2007

SUMMARY1. The influence of the passive force on the contraction and endothelium‐dependent relaxation in aortae of normotensive Wistar Kyoto (WKY) rats and stroke‐prone spontaneously hypertensive rats (SHRSP) were compared.2. Force changes of endothelium‐intact and ‐removed preparations were measured isometrically by a force‐displacement transducer. Endothelium‐dependent relaxation was observed by applying acetylcholine to the preparation precontracted in the presence of 5×10−7mol/L noradrenaline.3. The preparations showed spontaneously developed tension (tone) that increased with the increase in the passive force. The effect of passive force was greater in preparations from SHRSP. Contraction initiated by noradrenaline was also increased by passive force up to 30 mN, then showed a tendency to decrease.4. Endothelium‐dependent relaxation was depressed as the passive force was increased. Preparations from SHRSP showed impaired endothelium‐dependent relaxation and were influenced by passive force to a lesser degree when compared with preparations from WKY rats.5. Relaxation by sodium nitroprusside was influenced by passive force to a much lesser extent than that by acetylcholine.6. Indomethacin potentiated endothelium‐dependent relaxation and blocked the effect of passive force in both preparations.7. The difference in relaxation and the effect of passive force is primarily caused by the difference in the release of endo‐thelium‐derived contracting factor, which is thought to be a product of the cyclo‐oxygenase pathway of the arachidonic acid cascade.
DOWN‐REGULATION OF ANGIOTENSIN II RECEPTORS IN HYPERTROPHIED HUMAN MYOCARDIUM
Authors: Nozawa Yoshihisa , Miyake Hidekazu , Haruno Akihiro , Yamada Shizuo , Uchida Shinya , Ohkura Takashi , Kimura Ryohei , Suzuki Harumi , Hoshino Tsuneo 
Published: June 2007

SUMMARY1. Specific [125I]‐angiotensin II (AngII) binding in normal and hypertrophied human myocardial membranes was saturable and of high affinity. Low concentrations of unlabelled AngII and saralasin competed with [125I]‐AngII for the binding sites in these tissues. Thus, saturable [125I]‐AngII binding in human myocardium exhibited pharmacological specificity that characterized high affinity receptors for AngII.2. There was little difference in the apparent dissociation constant (Kd) values for [125I]‐AngII binding between normal and hypertrophied human myocardium, whereas the maximal number of binding sites (Bmax) was significantly (51%) lower in the hypertrophied group. Further, PD123177, a selective antagonist of the AT2 receptor subtype, showed three orders of magnitude higher affinity for [125I]‐AngII binding sites in both normal and hypertrophied myocardium than losartan, a selective antagonist of the AT1 receptor subtype; the Hill coefficients for these drugs were close to one.3. A significant decrease in Bmax and Kd values for (—)‐[125I]‐iodocyanopindolol binding between normal and hypertrophied human myocardium rarely occurred.4. The present study suggests that both normal and hypertrophied human myocardium predominantly contains the AT2 receptor subtype and that these receptors are down‐regulated in hypertrophied tissues.
OESTROGEN RECEPTORS AND CARDIOVASCULAR DISEASE*
Authors: Baysal Kemal , Losordo Douglas W 
Published: June 2007

SUMMARY1. Animal and human studies indicate that female sex hormones are protective against the development of coronary atherosclerosis.2. Experiments on vascular smooth muscle cells suggest a direct effect of oestrogen on vascular tissue. Although oestrogen receptors (ER) in vascular tissues and an association between ER stimulation and physiological effects have been demonstrated, the cellular mechanisms underlying the effects of oestrogen on the arterial wall remain to be defined.3. Elucidation of the cellular mechanism underlying the effects of oestrogen on vascular smooth muscle will provide insights into coronary atherosclerosis and will provide an opportunity to apply the protective effects of oestrogen to women in older age groups and to the male population.