bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subfornical organ lesion attenuates chronic hypotensive effects of losartan in salt-replete rats
Authors: Collister John P , Hendel Michael D 
Published: May 2007

Hypothesis/introduction Circumventricular organs are central nervous system brain sites thought to participate in neuroendocrine regulation of neural output. We have previously demonstrated a profound chronic hypotensive response to the angiotensin II (Ang II) AT1 antagonist, losartan (10 mg/kg/day), in normal rats. In addition, we have demonstrated that the area postrema, one of the circumventricular organs, partially mediates this response. The subfornical organ (SFO) is another circumventricular organ which has been shown to mediate actions of Ang II. The present study was designed to test the hypothesis that the SFO mediates the chronic hypotensive effects of losartan in normal rats. Materials and methods Rats were randomly chosen for lesion of the SFO or sham operation and instrumented with intravenous catheters and radiotelemetric blood pressure transducers. After a control period, rats were infused with losartan (10 mg/kg/day) for nine days. Mean arterial pressure and heart rate responses were measured continuously throughout the protocol and examined as 12-hour day/night averages. Results By day 7 of losartan treatment, night-time mean arterial pressure had dropped to 75±2 mmHg in sham rats (n=8) but only to 83±2 mmHg in SFO-lesioned rats (n=10). This trend continued throughout the treatment protocol. Conclusions These results suggest that the SFO partially mediates the chronic hypotensive effects of chronic losartan treatment in normal rats.
Vascular effects of quinapril completely depend on ACE insertion/deletion polymorphism
Authors: Voors Adriaan A , van Geel Peter P , Oosterga Margreeth , Buikema Hendrik , van Veldhuisen Dirk J , van Gilst Wiek H 
Published: May 2007

Introduction The angiotensin-converting enzyme (ACE) DD-genotype is associated with increased plasma and myocardial ACE-activity. The influence of the ACE insertion/deletion (I/D) polymorphism on the effects of ACE-inhibition on vascular responses has not been previously described. Materials and methods In the randomised, double-blind QUinapril On Vascular ACE and Determinants of Ischemia Study (QUO VADIS), 149 patients undergoing coronary bypass surgery were randomised to receive either the ACE inhibitor, quinapril, or placebo. In 82 patients, we obtained ACE-genotype, and measured vascular responses to angiotensin II (Ang II) in left internal mammary arteries. Results In the placebo group, the mean maximal vasoconstriction to Ang II was significantly lower in patients with the DD-genotype than in those with the ID/II genotype (36.2±5.11% [n=13] vs. 55.6±4.57% [n=25]; p=0.01). In the quinapril group, the mean maximal vasoconstriction to Ang II was similar [n=8] vs. 57.7±4.07% [n=35]; p=0.85). between DD- and ID/II-genotype (59.6±9.19% Conclusions DD-genotype patients showed decreased vascular responses to Ang II but treatment with quinapril completely restored the decreased vascular response in DD-genotype patients to the same level as II/ID-genotype patients, while no effect of quinapril was demonstrated in the II/ID-genotype patients.
How different urinary albumin excretion rates can predict progression to nephropathy and the effect of treatment in hypertensive diabetics
Authors: Huw Llewelyn DE , Garcia-Puig Juan 
Published: May 2007

Hypothesis The efficacy of a treatment in a clinical trial depends in part on where the cut-off point is placed for the test result used to select patients for the trial, and this applies to irbesartan in the Irbesartan Microalbuminuria II (IRMA II) trial for preventing nephropathy. Patients and methods Patients in the IRMA II trial were stratified into different pre-treatment albumin excretion rate (AER) ranges to compare the proportion of patients starting in these different ranges (i) that progressed to develop nephropathy within 24 months and (ii) whose AER was over 40 µg/minute at three months. Results The proportion of patients with pre-treatment AER values between 20 and 40 µg/minute progressing to develop nephropathy was 1.25% in the placebo group and 0.78% in the irbesartan group, while for pre-treatment AER values between 41 and 200 µg/minute, 24.4% and 11.2% develop nephropathy respectively in the placebo and irbesartan groups. In patients with a pre-treatment AER of 20 to 30 µg/minute, 32.5% and 13.6% respectively in the placebo and irbesartan groups had a value exceeding 40 µg/minute at three months. Conclusions The data demonstrate that irbesartan is effective in reducing the onset of nephropathy within two years when the pre-treatment AER is above 40 µg/minute, but if the AER is below this level it progresses unusually to nephropathy within two years. Irbesartan also slows progression of AER to over 40 µg/minute for patients with pre-treatment AER values at or above 20 µg/minute and these patients should be treated.
Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells
Authors: Richmond Renee S , Tallant E Ann , Gallagher Patricia E , Ferrario Carlos M , Strawn William B 
Published: May 2007

Introduction Angiotensin II (Ang II) is recognised as a regulator of haematopoiesis, but its actions within the bone marrow are not fully understood. Support of haematopoiesis by bone marrow stromal cells (MSC) is dependent on factors that include arachidonic acid and macrophage colony stimulating factor (MCSF), both of which are increased by Ang II stimulation in other tissues. To further elucidate the mechanisms of Ang II-regulated haematopoiesis, we determined whether Ang II-stimulation alters arachidonic acid release and MCSF secretion from MSC.Methods Cynomolgus monkey MSC isolated from bone marrow aspirates and the human HS-5 stromal cell line were studied for Ang II-mediated arachidonic acid (AA) release, while secretion of MCSF in response to Ang II was studied in HS-5 cells. Cells were labelled overnight with3H-AA and the release of3H-AA was measured in culture medium following 20 minutes stimulation with Ang II, alone or in combination with the AT1- or AT2-receptor antagonists, losartan and PD 123319, respectively. MCSF secretion into culture medium was measured using an enzyme immunoassay following 24 hours of treatment with Ang II alone or in combination with losartan or PD 123319. Phorbol-myristate-acetate, known to stimulate release of AA and MCSF, was used as a positive control in both experiments.Results In response to Ang II, release of3H-AA from monkey and human MSC was increased (p<0.05) to 147±4% and 124±3% of control, respectively. The AT1- and AT2-receptor antagonists, losartan and PD 123319, individually reduced Ang II-stimulated3H-AA release. In contrast, Ang II had no effect on secretion of MCSF from HS-5 cells.Conclusions These results provide mechanistic evidence for Ang II-mediated haematopoiesis through AA release that may, in part, explain Ang II-facilitated recovery of haematopoiesis in experimental myelosuppression and the anaemias associated with Ang II receptor blockade.
Does Angiotensin (1-7) Contribute to the Antiproteinuric Effect of ACE-inhibitors?
Authors: van der Wouden Els A , Henning Robert H , Deelman Leo E , Roks Anton JM , Boomsma Frans , de Zeeuw Dick 
Published: May 2007

Angiotensin-converting enzyme inhibitors (ACE-I) reduce proteinuria and protect the kidney in proteinuric renal disease. During ACE-I therapy, circulating levels of angiotensin (1-7) [Ang (1-7)] are increased. As cardiac and renal protective effects of Ang (1-7) have been reported, we questioned whether Ang (1-7) contributes to the antiproteinuric effects of ACE-I treatment. Therefore, we evaluated whether Ang (1-7) infusion reduces proteinuria in a rat model of adriamycin-induced renal disease. In addition, the effect of a selective Ang (1-7) blocker, [D-Ala7]-Ang (1-7) (A779), was investigated in rats treated with the ACE-I, lisinopril (LIS). Six weeks after induction of proteinuria, therapy was started in four different groups: control, Ang (1-7), LIS, and LIS+A779. After two weeks, the rats were sacrificed. Six weeks after injection of adriamycin, the rats had developed proteinuria of 323±40 mg/24 hours. The proteinuria remained stable in the control group and in the Ang (1-7) group, but was reduced in both LIS and LIS+A779-treated groups. Similarly, blood pressure (BP) was unchanged in the control and the Ang (1-7) groups, but reduced in both the LIS and the LIS+A779 groups. Plasma levels of Ang (1-7) were increased in the Ang (1-7) and in both LIS-treated groups. We conclude that systemic Ang (1-7) plays no major role in the antiproteinuric and BPlowering effects of ACE-I in this rat model of adriamycin-induced nephrosis.
Aldosterone Blockade Over and Above ACE-Inhibitors in Patients with Coronary Artery Disease but without Heart Failure
Authors: Shah Nimit C , Pringle Stuart , Struthers Allan 
Published: May 2007

Recent evidence points to a role for the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of atherosclerosis and its complications, including acute angina pectoris. Two large trials in heart failure have clearly demonstrated that blocking aldosterone improves mortality1,2 and that this benefit occurs over and above standard therapy with angiotensin-converting enzyme (ACE) inhibitors. The question that naturally arises from these landmark studies is whether aldosterone blockade would produce the same benefits in patients with coronary artery disease (CAD) but no heart failure. There are three reasons to believe this might be the case. Firstly, angiotensin II (Ang II) and aldosterone produce similar biological effects and Ang II withdrawal has been shown to benefit patients with angina; aldosterone blockade may therefore follow in the footsteps of ACE inhibitors, as it did in heart failure, and produce benefits in vascular patients without heart failure. Secondly, one of the main mechanisms which is thought to be responsible for the benefit of aldosterone blockade in the Randomised ALdactone Evaluation Study (RALES) and Eplerenone Post-AMI Heart Failure Survival Study (EPHESUS), is that it improves endothelial/ vascular function3,4 and endothelial/vascular dysfunction is the fundamental abnormality in angina pectoris. Finally, aldosterone blockade has been shown to reduce atherosclerosis in animal studies of atherosclerosis without heart failure, which are analogous to CAD patients.5
Renal Haemodynamics are not Related to Genotypes in Offspring of Parents with Essential Hypertension
Authors: Skov Karin , Madsen Jens Kristian , Hansen Hans Erik , Zagato Laura , Frandsen Erik , Bianchi Giuseppe , Mulvany Michael John 
Published: May 2007

Introduction. The pathogenesis of essential hypertension (EH) has a major genetic component and is associated with renal abnormalities. Normotensive offspring of hypertensive parents are likely to develop EH and are a suitable population for identifying possible relations between genetic and renal abnormalities. Methods. We investigated if renin-angiotensin-aldosterone system associated genotypes (angiotensinogen [M235T] and ACE [I/D]) are related to blood pressure (BP), renal haemodynamics and sodium excretion in sex and age-matched (18—35 years) healthy Caucasian offspring of either two parents with EH (n=101, EH-offspring) or two normotensive parents (n=50, controls). The alpha-adducin polymorphism (G460W) was also investigated. Results. Compared to controls, BP, heart rate, renal vascular resistance (RVR) and urinary sodium excretion were, respectively, 5%, 7%, 15% and 20% higher in EH-offspring. In controls, the TT-genotype of the M235T angiotensinogen polymorphism was associated with higher BP and higher plasma angiotensinogen. By contrast, in EHoffspring the TT-genotype was associated with lower BP and unchanged plasma angiotensinogen. Plasma angiotensinogen correlated positively with BP in EH-offspring, with a similar tendency (p=0.08) in controls. The distributions of the three candidate polymorphisms were similar in EH-offspring and controls. There were no associations between any of the polymorphisms and any of the renal parameters measured. Conclusion. The markedly greater RVR, proportionally larger than the greater BP, supports a role for RVR in the pathogenesis of EH. The lack of association between the candidate polymorphisms and the investigated parameters, even in this homogenous and for hypertension strongly predisposed group, suggests that the polymorphisms investigated do not play important roles in the pathogenesis of hypertension.
Chronic blockade of angiotensin II AT1-receptors increased cell-to-cell communication, reduced fibrosis and improved impulse propagation in the failing heart
Authors: De Mello Walmor C 
Published: May 2007

Introduction. The influence of chronic administration of losartan on gap junction conductance (gj), conduction velocity and interstitial fibrosis was investigated in the failing heart of 4-month-old cardiomyopathic hamsters (TO-2).After two months of administration of losartan (25 mg/kg/day/po) the number of cell pairs showing very low values of gj (2—8 nS) was significantly reduced whereas the group of cell pairs with larger values of gj (18-45 nS) was significantly increased.The conduction velocity measured with intracellular microelectrodes in the wall of the left ventricle was enhanced from 38+2.3 cm/s (n=25) (control) to 49+2 cm/s (n=24) (p<0.05) after losartan administration. Moreover, the number of ventricular fibres showing non-propagated action potentials was significantly decreased (p<0.05) by losartan.The % area of interstitial fibrosis measured in the wall of the left ventricle was reduced from 22+1.4% (n=18) to 14 1.3% (n=18) (p<0.05) after losartan administration. Conclusion. Chronic blockade of angiotensin II type 1 receptors increased gj in the failing heart. Moreover,the conduction velocity was enhanced remodelling in part by the increase of gj and in part by the decrease of interstitial fibrosis and structural remodelling.
The angiotensin type 1 receptor antagonist valsartan attenuates pathological ventricular hypertrophy induced by hyperhomocysteinemia in rats
Authors: Kassab Salah , Garadah Taysir , Abu-Hijleh Marwan , Golbahar Jamal , Senok Solomon , Wazir Javed , Gumaa Khalid 
Published: May 2007

Introduction. Clinical and experimental studies have reported the role of homocysteine in ventricular hypertrophy. Activation of the reninangiotensin system mediated by angiotensin II type 1 (AT1) receptor has also been suggested to contribute to the pathogenesis of ventricular hypertrophy. There are also reports suggesting the affect of angiotensin II (Ang II) on cardiac hypertrophy is mediated by hyperhomocysteinemia. However, there is limited information on the mechanisms of the possible relationship between homocysteine and Ang II in ventricular hypertrophy. In this study we tested the hypothesis that hyperhomocysteinemia induced ventricular hypertrophy and remodelling may be mediated through activation of Ang II AT1-receptors in rats. Methods. This study was conducted on control non-treated rats (n=13), methionine-treated rats (1.5 mg/kg/day, n=18) and methionine plus oral AT1 antagonist (valsartan, 30 mg/kg/day, n=13) treated rats for 56 days. Systolic blood pressure (SBP) was determined in rats at baseline, 28 and 56 days. Echocardiography was also performed in all rats after eight weeks, and blood samples were obtained for determination of plasma tHcy. Rats were then sacrificed for histopathological and biochemical assessment of cardiac structure. Results. The SBP in the methionine-treated rats was significantly higher compared with controls and significantly lower compared with the methionine-valsartan group at 28 and 56 days (p<0.001). In addition, left ventricular wall thickness (LVWT) in the methionine-valsartan group (4.36±0.11 mm) was significantly lower compared with the methionine group (5.0±0.23 mm, p=0.03). Furthermore, cardiac collagen to total protein ratio was significantly lower in the methionine-valsartan group (2.19±0.11%) compared with the methionine group (2.64±0.08%, p=0.026). Fractional shortening (FS) was not significantly different between groups. Conclusion. Results from this study suggest that hyperhomocysteinemia-induced hypertension and ventricular hypertrophy in rats are mediated, at least partly; by Ang II activation of AT1-receptors.
The effects of telmisartan and amlodipine on metabolic parameters and blood pressure in type 2 diabetic, hypertensive patients
Authors: Negro Roberto , Hassan Haslinda 
Published: May 2007

Introduction. Hypertension in type 2 diabetes represents a strong risk factor for cardiovascular events. Either calcium channel blockers or angiotensin receptor blockers (ARBs) may reduce insulin resistance. One of the ARBs, telmisartan (Telm) acting as a PPARγ agonist, significantly reduces HbA1C levels.The aim of this study was the comparison of the effects on glycaemic control of amlodipine (Aml) and Telm in hypertensive type 2 diabetic patients. Materials and methods. Forty diabetic hypertensive subjects were assigned to two groups. Group A: rosiglitazone (RSG) 4 mg + Telm 80 mg; Group B: RSG 4 mg + Aml 10 mg. All the patients were already treated with metformin, but not with antihypertensive drugs. Results. After four months treatment, both groups showed a significant reduction of mean blood pressure (Group A: - 13.5%; Group B: - 13.3%) and a positive influence on glycaemic control and insulin resistance. Lower values of glucose, HbA1C, HOMA index and higher adiponectin levels were observed in Group A compared to Group B. Conclusions. In type 2 diabetic hypertensive patients, the association of Telm 80 mg and RSG 4 mg seems to display a metabolic advantage compared to Aml 10 mg.The simultaneous beneficial effects on blood pressure and insulin sensitivity may confer make Telm particularly suitable in the treatment of the metabolic syndrome.
Review: Lisinopril in paediatric medicine: a retrospective chart review of long-term treatment in children
Authors: Raes Ann , Malfait Franciska , Van Aken Sarah , France Annick , Donckerwolcke Raymond , Vande Walle Johan 
Published: May 2007

Objective. To investigate the antihypertensive efficacy, dosing, tolerability and effects on growth of lisinopril (off label-use) in paediatric patients during long-term treatment. Design. We conducted a retrospective analysis of data from 123 patients treated with lisinopril in a paediatric nephrology clinic over a 9.3-year period. Patients were categorised by age group and predominant clinical diagnosis: hypertension (n=59), renal parenchymal disease (n=27), diabetes mellitus (n=33) and miscellaneous (n=4). Results. The vast majority were Caucasian (93%) and boys (66%). Mean duration of treatment was 2.0 years. Age at start of treatment ranged from two months to 17.7 years. Mean lisinopril starting and final doses were 0.105 mg/kg/day for hypertensive patients and 0.108 mg/kg/day for patients with renal disease, respectively. The most common adverse event was hypotension (8.6% of the patients). Haematology and serum biochemistry profiles were unaffected by lisinopril. Growth was not different from data recorded by Belgian population studies. In 29 of the 47 hypertensive patients who received lisinopril monotherapy, comparing blood pressure (BP) at baseline and after six months' treatment, mean reductions in systolic/diastolic BP were 19/18 mmHg. Conclusions. Lisinopril was well tolerated in paediatric patients. Doses of 0.1 mg/kg/day produced clinically significant BP reduction in hypertensive patients.
Cover Picture: Formation of Well‐Organized Self‐Assembled Films from Peptide Nanotubes (Adv. Mater. 11/2007)
Authors: Hendler N. , Sidelman N. , Reches M. , Gazit E. , Rosenberg Y. , Richter S. 
Published: May 2007

AbstractDiphenylalanine‐peptide nanotubes can form well‐organized spherulitic films several centimeters in size while preserving the original crystallographic structure of the nanotube, as reported on p. 1485 by Shachar Richter and co‐workers. An optical microscopy image shows the early growth stages of such a film (image taken at the Scientific Photography Lab, Weizmann Institute of Science, Rehovot, Israel).
Fluorapatite‐Supported Palladium Catalyst for Suzuki and Heck Coupling Reactions of Haloarenes
Authors: Kantam M. Lakshmi , Kumar K. B. Shiva , Srinivas P. , Sreedhar B. 
Published: May 2007

AbstractA fluorapatite‐supported palladium catalyst (PdFAP) was synthesized by treatment of fluorapatite (prepared by incorporating the basic species fluoride ion into apatite in situ by co‐precipitation) with bis(benzonitrile)palladium(II) chloride in acetone. The catalyst displayed high catalytic activity for Suzuki coupling of aryl iodides and bromides with boronic acids at room temperature and chloroarenes at 130 °C in the presence of tetrabutylammonium bromide to give biaryls in excellent yields. Heck olefination of chloroarenes was also successfully carried out by this catalyst. PdFAP was recovered quantitatively by simple filtration and reused with consistent activity. PdFAP was well characterized by XRD, FTIR, XPS, ICP‐AES, CO2 TPD and CHN elemental analysis.
Osmium‐Catalyzed Selective Oxidations of Methane and Ethane with Hydrogen Peroxide in Aqueous Medium
Authors: Yuan Qiang , Deng Weiping , Zhang Qinghong , Wang Ye 
Published: May 2007

AbstractVarious transition metal chlorides including FeCl3, CoCl2, RuCl3, RhCl3, PdCl2, OsCl3, IrCl3, H2PtCl6, CuCl2 and HAuCl4 were studied for the selective oxidations of methane and ethane with hydrogen peroxide in aqueous medium. Among the metal chlorides investigated, osmium(III) chloride (OsCl3) exhibited the highest turnover frequency (TOF) for the formation of organic oxygenates (mainly alcohols and aldehydes) from both methane and ethane. For the OsCl3‐catalyzed oxidation of methane with hydrgen peroxide, methyl hydroperoxide was also formed together with methanol and formaldehyde. The effects of various kinetic factors on the catalytic behavior of the OsCl3‐H2O2 system were investigated, and TOF values of 12 and 41 h−1 could be obtained for oxygenate formation during the oxidations of methane and ethane, respectively. In the presence of OsCl3, NaClO, NaClO4 or NaIO4 as oxidant was incapable of oxidizing methane and ethane to the corresponding oxygenates, and the use of tert‐butyl hydroperoxide (TBHP) instead of H2O2 provided remarkably lower rates of formation of oxygenates. UV‐Vis spectroscopic measurements suggested that OsCl3 was probably oxidized into an Os(IV) species by H2O2 in aqueous medium, and the Os(IV) species might be involved in the oxygenation of methane or ethane. The result that the conversions of both methane and ethane to oxygenates were suppressed by the addition of a radical scavenger suggested that the reactions proceeded via a radical pathway.
Formation of Arenes via Diallylarenes: Strategic Utilization of Suzuki–Miyaura Cross‐Coupling, Claisen Rearrangement and Ring‐Closing Metathesis
Authors: Kotha Sambasivarao , Shah Vrajesh R. , Mandal Kalyaneswar 
Published: May 2007

AbstractTwo new synthetic strategies for benzoannulation are reported. The first strategy is based on the Suzuki–Miyaura cross‐coupling reaction. To this end, various ortho‐diallylbenzene derivatives were prepared from the corrresponding diiodo derivatives by an allylation strategy using an allylboronate as coupling partner. These diallyl derivatives were subjected to a ring‐closing metathesis (RCM) and one‐pot dichlorodicyanoquinone (DDQ) oxidation sequence to deliver 2‐substituted naphthalenes. In the second strategy, a double Claisen rearrangement and RCM protocol have been used as key steps to give highly functionalized benzoannulated quinone derivatives.