bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-ion mass spectrometry at 100 ppt and beyond
Authors: Rainville S , Thompson J K , Pritchard D E
Published: December 2002

Using a Penning trap single-ion mass spectrometer, we measured the atomic masses of 14 isotopes with a fractional accuracy of ~1010. The precision on these measurements was limited by the temporal fluctuations of our magnetic field. By trapping two different ions in the same Penning trap at the same time, we have recently been able to virtually eliminate that source of error. We can now simultaneously measure the ratio of the two ion's cyclotron frequencies (from which we obtain their atomic mass ratio) with a precision of about 1011 in only a few hours. To perform these comparisons, we must be able to measure and control all three normal modes of motion of each ion  cyclotron, axial, and magnetron  and have developed novel techniques to do so. This new technique shows promise of expanding the precision of mass spectrometry by an order of magnitude beyond the current state-of-the-art.

PACS Nos.: 32.10Bi, 06.20Jr, 06.30Dr, 07.75+h, 07.77-n
Progress in helium fine-structure calculations and the fine-structure constant
Authors: Drake G WF
Published: December 2002

The long-term goal of this work is to determine the fine-structure constant α from a comparison between theory and experiment for the fine-structure splittings of the helium 1s2p 3PJ states. All known terms of order α5 a.u. (α7 mc2) arising from the electronelectron interaction, and recoil corrections of order α4 µ / M a.u. are evaluated and added to previous tabulation. The predicted energy splittings are ν0,1 = 29 616.946 42(18) MHz and ν1,2 = 2291.154 62(31) MHz. Although the computational uncertainty is much less than ±1 kHz, there is an unexplained discrepancy between theory and experiment of 19.4(1.4) kHz for ν1,2.

PACS Nos.: 31.30Jv, 32.10Fn
Gyromagnetic factors of bound particles with arbitrary spin in quantum electrodynamics
Authors: Faustov R N , Martynenko A P
Published: December 2002

A quasipotential method is formulated for calculating relativistic and radiative corrections to the magnetic moment of a two-particle bound state in the case of particles with arbitrary spin. It is shown that the g factors of bound particles contain O(α2) terms depending on the particle spin. Numerical values for the g factors of the electron in the hydrogen atom and deuterium are obtained.

PACS Nos.: 31.30Jv, 12.20Ds, 32.10Dk
WRINGING OUT NEW BELL INEQUALITIES FOR THREE-DIMENSIONAL SYSTEMS (QUTRITS)
Authors: CHEN JING-LING , KASZLIKOWSKI DAGOMIR , KWEK L. C. , OH C. H.
Published: December 2002

We briefly trace the progress in study of Bell–CH inequalities from two-level systems to its higher dimensional versions. We also present a Bell–CH and CHSH-like inequality for three-dimensional systems.
SEARCHING FOR NEW PHYSICS IN LEPTONIC DECAYS OF BOTTOMONIUM
Authors: SANCHIS-LOZANO MIGUEL ANGEL
Published: December 2002

New physics can show up in various well-known processes already studied in the Standard Model, in particular by modifying decay rates to some extent. In this work we examine leptonic decays of ϒ resonances of bottomonium below [Formula: see text] production, subsequent to a magnetic dipole radiative structural transition of the vector resonance yielding a pseudoscalar continuum state, searching for the existence of a light Higgs-like neutral boson that would imply a slight but experimentally measurable breaking of lepton universality.
Return, Volatility and Short-term Capital Inflows: A Test of "Return-Chasing" Hypothesis in Asia-Pacific Equity Markets
Authors: Tu Anthony H. , Chen Shen-Yuan
Published: December 2002

The increased flows of securities investment have shifted from developed countries to emerging ones over the last decade. Capital flows to developing countries have important benefits. However, large surges in short-term and potentially reversible capital flows can have very negative effects. The idea of this study is to assess the empirical evidence in Asia-Pacific developed and emerging markets for whether the "return-chasing" hypothesis is true? The conditional variance in the model is assumed to follow a generalized ARCH-M model, including country credit ratings as explanatory risk variables in the mean and variance equations. The results suggest that the relationship between country index returns and return variance are weak for both developed and emerging markets. The changes of country credit ratings have positive impacts on country index returns in some Asian emerging markets, but not in developed markets. We also found that the changes of country credit ratings have significant influence, but with mixed sign, on country index return volatility for some Asian emerging markets, but not for developed markets. The findings support the "return-chasing" hypothesis, in which the flow securities investment tends to move into the markets whose returns are expected to be high and retreat from markets whose returns are predicted to be low. The result suggests that the world community and national authorities have to manage these flows more effectively. There exists a serious risk that such volatile flows could undermine the benefits that globalization and free markets can otherwise bring.
High Capacity Surface-Modified LiCoO2 Cathodes for Lithium-Ion Batteries
Authors: Kannan A. M. , Rabenberg L. , Manthiram A.
Published: December 2002

The surface of

LiCoO

2

cathodes was modified with

Al

2

O

3

,

TiO

2

,

and

ZrO

2

by a chemical processing procedure followed by heat treatment at 300°C in air for 4 h. The surface-modified

LiCoO

2

samples show much better capacity retention at both 25 and 60°C than the unmodified

LiCoO

2

cathode to higher cutoff charge voltages of as high as 4.7 V vs. lithium. For example,

Al

2

O

3

-modified

LiCoO

2

shows approximately 180 mAh/g at 4.5 to 3.2 V with a capacity fade of only 8% in 100 cycles, compared to 32% for the unmodified

LiCoO

2

.

Transmission electron microscopic studies reveal that the guest materials are present as loose oxides

(

Al

2

O

3

and

ZrO

2

)

or as monolayers

(

TiO

2

)

on the surface of

LiCoO

2

particles. The improved capacity retention and the higher reversible capacity (180 mAh/g) of the surface-modified

LiCoO

2

compared to the unmodified

LiCoO

2

(140 mAh/g) could be due to a suppression of the chemical and structural instabilities of the charged

Li

1
−
x

CoO

2

cathodes and/or reduction of interparticle stresses and strains. © 2003 The Electrochemical Society. All rights reserved.
Expression of G2A, a Receptor for Lysophosphatidylcholine, by Macrophages in Murine, Rabbit, and Human Atherosclerotic Plaques
Authors: Rikitake Yoshiyuki , Hirata Ken-ichi , Yamashita Tomoya , Iwai Kenji , Kobayashi Seiichi , Itoh Hiroshi , Ozaki Masanori , Ejiri Junya , Shiomi Masashi , Inoue Nobutaka , Kawashima Seinosuke , Yokoyama Mitsuhiro
Published: December 2002

Objective—

Lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low density lipoprotein, has been demonstrated to induce multiple functional alterations of vasculature that are potentially involved in atherosclerosis. Recently, an orphan G-protein-coupled receptor, G2A, has been identified as a high-affinity receptor for LPC. Although it has been demonstrated that G2A is expressed predominantly in lymphoid tissues and lymphocytes, there are no reports to determine whether G2A is expressed in atherosclerotic lesions and cardiovascular cells.

Methods and Results—

Immunohistochemistry with an anti-G2A antibody revealed that G2A was expressed predominantly by macrophages within atherosclerotic lesions at the aortic root of apolipoprotein E-deficient mice and the thoracic aortas of Watanabe heritable hyperlipidemic rabbits. In atherosclerotic plaques of human coronary arterial specimens, G2A was expressed by macrophages within the lipid-rich plaques, whereas no immunoreactivity of G2A was observed in fibrous plaques where macrophages did not exist. Reverse transcription-polymerase chain reaction analysis demonstrated that G2A mRNA was highly expressed in human and murine monocytes/macrophages. The expression of G2A protein was detected in human and murine monocytes/macrophages by immunoblotting.

Conclusions—

These findings demonstrate that monocytes/macrophages abundantly express G2A and suggest that G2A may play a role in the formation and progression of atherosclerotic lesions.
Gene Expression Profiling of Apoptosis-Related Genes in Human Atherosclerosis
Authors: Martinet Wim , Schrijvers Dorien M. , De Meyer Guido R.Y. , Thielemans Jeff , Knaapen Michiel W.M. , Herman Arnold G. , Kockx Mark M.
Published: December 2002

Objective—

Apoptosis substantially affects the cellularity and integrity of atherosclerotic plaques. It remains, however, unclear which key regulatory genes are involved. In this study, cDNA expression arrays were used to analyze transcript levels of 205 apoptosis-related genes in human carotid endarterectomy specimens versus nonatherosclerotic mammary arteries.

Methods and Results—

Seventeen genes with a 2- to 5-fold relative expression difference were identified. One of the most apparent changes in human plaques was the overexpression of death-associated protein (DAP) kinase (≈5-fold), a positive mediator of apoptotic cell death. Differential expression of DAP kinase mRNA in human plaques relative to mammary arteries was confirmed by quantitative reverse-transcription polymerase chain reaction. Western blotting and immunohistochemistry demonstrated enhanced levels of DAP kinase protein in the plaque with negligible expression in non-atherosclerotic vessels. DAP kinase was located predominantly in foam cells of smooth muscle cell (SMC) origin. Uptake of aggregated LDL by cultured aortic SMCs as well as exposure of SMCs to the short-chain acyl ceramide derivative
N
-hexanoyl-
d
-sphingosine (C
6
-ceramide) upregulated DAP kinase both at the mRNA and protein level.

Conclusions—

Our data demonstrate that cDNA array technology can identify novel genes that might participate in cell death pathways underlying atherogenesis.
Remodeling of Small Intramyocardial Coronary Arteries Distal to a Severe Epicardial Coronary Artery Stenosis
Authors: Hong Huashan , Aksenov Sergei , Guan Xiaoming , Fallon John T. , Waters David , Chen Chunguang
Published: December 2002

Objective—

Impaired coronary blood flow (CF) or flow reserve with incomplete and delayed recovery of left ventricular (LV) function after revascularization is common in severe ischemic LV dysfunction. The underlying mechanism is not fully known. We studied structural changes of small intramyocardial coronary arteries (SIMCAs) in a pig model of chronic coronary stenosis, testing the hypothesis that microvascular remodeling develops distally to a severe epicardial coronary artery stenosis.

Methods and Results—

A total of 24 pigs were studied in 3 groups. Left anterior descending coronary stenosis was created to reduce CF by a mean of ≈30%, producing severe regional systolic dysfunction without infarction. The stenosis was maintained for 7 days in 6 pigs (Group 1) and for 4 weeks in 12 pigs (Group 2). The control group (Group 3) consisted of 6 pigs with the same surgical procedures but without stenosis. The wall thickness (WTa) and lumen (L) diameter of SIMCA were measured, and the ratio of WTa/L and lumen area/total vessel area (% lumen) were calculated. The composition of the arterial wall was studied with cell proliferation markers Ki67 and BrdU. The immediate reduction in CF after the creation of the stenosis was similar in both study groups, but after the first week, CF decreased significantly (
P
<0.05) when the stenosis was maintained (group 2). The left anterior descending stenosis caused regional LV dysfunction in all pigs (groups 1 and 2). After 4 weeks of stenosis with chronic myocardial hibernation (group 2), but not after 1 week (group 1), WTa and WTa/L increased and L decreased significantly in the chronic hibernating region located distally to the stenosis, compared with both the control (group 3) and the normal region in the same pig. The mean % lumen of SIMCA per pig correlated with the CF reduction (
r
=0.92,
P
<0.001) and with myocardial fibrosis (
r
=0.82,
P
<0.01) in the 4-week stenosis group. Ki67- and BrdU-positive cells were increased in the wall of SIMCA in Group 1 and 2 compared with the control group (
P
<0.01 for each). The proliferated cells were stained positively with smooth muscle α-actin antibody.

Conclusion—

In the chronic ischemic, hibernating myocardial region distal to a flow-limiting epicardial coronary stenosis, the small intramyocardial coronary arteries undergo remodeling, with an increase in wall thickness and a decrease in lumen. These structural changes may further restrict blood flow to ischemic myocardium and may account for the pathophysiologic impairment of CF or flow reserve after revascularization, which leads to delayed or incomplete recovery of myocardial function.
Flow Loading Induces Macrophage Antioxidative Gene Expression in Experimental Aneurysms
Authors: Nakahashi Takeshi K. , Hoshina Katsuyuki , Tsao Philip S. , Sho Eiketsu , Sho Mien , Karwowski John K. , Yeh Cory , Yang Ruey-Bing , Topper James N. , Dalman Ronald L.
Published: December 2002

Objective—

Reactive oxygen species may act as proinflammatory mediators in abdominal aortic aneurysm (AAA) disease. Flow loading increases antioxidative enzyme expression and limits reactive oxygen species production in vascular smooth muscle cells in vitro, limits experimental AAA enlargement in rodent models, and is indirectly associated with reduced clinical AAA risk. We attempted to determine the mechanism or mechanisms by which flow loading limits AAA enlargement.

Methods and Results—

Rodent AAAs were flow loaded via femoral arteriovenous fistula creation. Aortic wall shear stress and relative wall strain were significantly higher in flow-loaded rodents. Flow loading reduced AAA diameter by 26% despite evidence of flow-mediated aortic enlargement proximal to the aneurysmal segment. Messenger RNA from AAA tissue was harvested for cDNA labeling and hybridization to a 384-clone DNA microarray. Twenty-nine genes were differentially expressed (relative intensity/relative intensity of control ratio >1.5 and <0.67) in flow-loaded compared with normal flow AAA tissue, including heme oxygenase 1 (HO-1). Increased HO-1 expression was confirmed via reverse transcriptase–polymerase chain reaction. Immunohistochemistry localized HO-1 expression to infiltrative macrophages. α-Tocopherol was found to be as effective as flow loading in limiting AAA enlargement. Flow loading and α-tocopherol therapy reduced AAA reactive oxygen species production.

Conclusions—

Flow loading may attenuate AAA enlargement via wall shear or strain-related reductions in oxidative stress.
Thrombosis Increases Circulatory Hepatocyte Growth Factor by Degranulation of Mast Cells
Authors: Kinoshita Makoto , Miyamoto Tadashi , Ohashi Naohiro , Sasayama Shigetake , Matsumori Akira
Published: December 2002

Background—

Plasma concentrations of hepatocyte growth factor (HGF), a powerful angiogenic growth factor inducible by heparin, increase in thrombus-associated disorders such as myocardial infarction and unstable angina. The mechanism of this thrombus-associated HGF release, however, is unknown.

Methods and Results—

Wistar rats received through the tail vein (1) normal saline (NS), (2) 50 μg of the mast cell–degranulating agent CP48/80, or (3) 1000 U/kg heparin. Blood samples were collected at 10 minutes or 30 minutes after the injections, or from untreated rats, for measurements of HGF. The same experiments were performed in mast cell–deficient white spotting (Ws) rats. Ws rats have a small deletion of the c-kit gene and are deficient in mast cells. Intravenous heparin immediately increased plasma HGF in both Wistar (38.02±2.08 ng/mL versus 1.11±0.70 ng/mL in untreated rats,
P
<0.0001) and Ws rats (36.39±4.15 ng/mL versus 0.66±0.18 ng/mL in NS-treated rats,
P
<0.0001). Injection of CP48/80 also increased plasma HGF in Wistar rats (9.12±1.11 ng/mL versus 0.65±0.24 ng/mL in NS group,
P
=0.004) but not in Ws rats (0.67±0.27 ng/mL versus 0.66±0.18 ng/mL in NS group,
P
=0.997). In a rat carotid artery microthrombus model, intra-arterial thrombus formation increased circulating HGF in Wistar rats (2.12±0.70 ng/mL versus sham 0.61±0.15 ng/mL in sham-operated Wistar rats,
P
=0.0064) but not in Ws rats (0.76±0.33 ng/mL versus 0.21±0.04 ng/mL in sham-operated Ws rats,
P
=0.29). In addition, in vitro stimulation of rat peritoneal mast cells with thrombin rapidly induced degranulation in a dose-dependent manner.

Conclusions—

These observations indicate that mast cell degranulation stimulated by thrombin is necessary for the rapid induction of plasma HGF in intravascular thrombus-associated disorders.
PPARα Activator Effects on Ang II–Induced Vascular Oxidative Stress and Inflammation
Authors: Diep Quy N. , Amiri Farhad , Touyz Rhian M. , Cohn Jeffrey S. , Endemann Dierk , Neves Mario Fritsch , Schiffrin Ernesto L.
Published: December 2002

Docosahexaenoic acid (DHA), a peroxisome proliferator–activated receptor-α (PPARα) activator, reduces blood pressure (BP) in some hypertensive models by unclear mechanisms. We tested the hypothesis that DHA would prevent BP elevation and improve vascular dysfunction in angiotensin (Ang) II–infused rats by modulating of NADPH oxidase activity and inflammation in vascular wall. Sprague-Dawley rats received Ang II (120 ng/kg per minute SC) with or without DHA (2.5 mL of oil containing 40% DHA/d PO) for 7 days. Systolic BP (mm Hg), elevated in Ang II–infused rats (172±3) versus controls (108±2,
P
<0.01), was reduced by DHA (112±4). In mesenteric small arteries studied in a pressurized myograph, media/lumen ratio was increased (
P
<0.05) and acetylcholine-induced relaxation impaired in Ang II–infused rats (
P
<0.05); both were normalized by DHA. In blood vessels of Ang II–infused rats, NADPH oxidase activity measured by chemiluminescence and expression of adhesion molecules intercellular adhesion molecule and vascular cell adhesion molecule-1 were significantly increased. These changes were abrogated by DHA. PPARα activator DHA attenuated the development of hypertension, corrected structural abnormalities, and improved endothelial dysfunction induced by Ang II. These effects are associated with decreased oxidative stress and inflammation in the vascular wall.
AVE 0991, a Nonpeptide Mimic of the Effects of Angiotensin-(1–7) on the Endothelium
Authors: Wiemer Gabriele , Dobrucki Lawrence W. , Louka Febee R. , Malinski Tadeusz , Heitsch Holger
Published: December 2002

Recently, we demonstrated that the heptapeptide angiotensin-(1–7) (Ang-[1–7]) exhibits a favorable kinetic of nitric oxide (NO) release accompanied by extremely low superoxide (O
2
−
) production. In this report we describe AVE 0991, a novel nonpeptide compound that evoked effects similar to Ang-(1–7) on the endothelium. AVE 0991 and unlabeled Ang-(1–7) competed for high-affinity binding of [
125
I]-Ang-(1–7) to bovine aortic endothelial cell membranes with IC
50
values of 21±35 and 220±280 nmol/L, respectively. Stimulated NO and O
2
−
release from bovine aortic endothelial cells was directly and simultaneously measured on the cell surface by selective electrochemical nanosensors. Peak concentrations of NO and O
2
−
release by AVE 0991 and Ang-(1–7) (both 10 μmol/L) were not significantly different (NO: 295±20 and 270±25 nmol/L; O
2
−
: 18±2 and 20±4 nmol/L). However, the released amount of bioactive NO was ≈5 times higher for AVE 0991 in comparison to Ang-(1–7). The selective Ang-(1–7) antagonist [D-Ala
7
]-Ang-(1–7) inhibited the AVE 0991–induced NO and O
2
−
production by ≈50%. A similar inhibition level was observed for the Ang II AT
1
receptor antagonist EXP 3174. In contrast, the Ang II AT
2
receptor antagonist PD 123,177 inhibited the AVE 0991–stimulated NO production by ≈90% but without any inhibitory effect on O
2
−
production. Both NO and O
2
−
production were inhibited by NO synthase inhibition (≈70%) and by bradykinin B
2
receptor blockade (≈80%). AVE 0991 efficiently mimics the effects of Ang-(1–7) on the endothelium, most probably through stimulation of a specific, endothelial Ang-(1–7)-sensitive binding site causing kinin-mediated activation of endothelial NO synthase.
Loss of Chromosome 16 From Renal Epithelial Cells in Humans
Authors: Gardner Jeffrey P. , Yang Xiao-Yan , Skurnick Joan , Wilson Patricia D. , Aviv Hana , Patel Smita , Davidow Amy L. , Gutkin Michael , Aviv Abraham
Published: December 2002

This work explores the notion that low-frequency, acquired aneuploidy may play a role in complex genetic traits such as essential hypertension. To this end, renal epithelial cells in urinary sediments and in renal cysts were examined by fluorescent in situ hybridization with DNA probes specific for the heterochromatic and centromere regions of chromosomes 16 and 1. Chromosome 16 was probed because it harbors variant genes causing monogenic hypertension. These genes have also been investigated for their role in essential hypertension. Chromosome 1 was also probed as an internal control. Higher proportions of renal epithelial cells in the urinary sediments showed monosomy of chromosome 16 than monosomy of chromosome 1 (
P
<0.001). We also observed in epithelial cells of renal cysts a preponderance of monosomy for chromosome 16 over monosomy for chromosome 1 (
P
<0.024). Low-frequency loss of heterozygosity that results from acquired monosomy of chromosome 16 and perhaps other chromosomes may contribute to expression of complex genetic traits such as essential hypertension, in which the diverse phenotypic manifestations are poorly understood.
Lack of Long-Term Effect of Vitamin C Supplementation on Blood Pressure
Authors: Kim Mi Kyung , Sasaki Satoshi , Sasazuki Shizuka , Okubo Shunji , Hayashi Masato , Tsugane Shoichiro
Published: December 2002

In a double-blinded randomized controlled trial, we investigated the long-term effect of vitamin C supplementation on blood pressure. A total of 439 Japanese subjects with atrophic gastritis initially participated in the trial using vitamin C and β-carotene to prevent gastric cancer. Before and on early termination of β-carotene supplementation, 134 subjects dropped out of this trial, whereas 120 and 124 subjects took the vitamin C supplement daily at either 50 mg or 500 mg, respectively, for 5 years. Before supplementation, neither systolic nor diastolic blood pressure was significantly related with the serum vitamin C concentration. This relationship was unchanged after adjustment for age, body mass index, and alcohol intake or after stratification by gender. After 5 years, systolic blood pressure significantly increased in groups, regardless of vitamin C dose, compared with baseline. Systolic blood pressure in the high-dose group (500 mg daily) increased from 125.4 to 131.7 mm Hg (5.88 mm Hg increase; 95% confidence interval [CI], 3.11 to 8.65). This value was similar with that of the low-dose group (5.73 mm Hg increase; 95% CI, 2.62 to 8.83) and of the dropout group (4.52 mm Hg increase; 95% CI, 1.26 to 7.77). There was no difference in change of diastolic blood pressure among the 3 groups. In conclusion, we observed no reduction in blood pressure with long-term moderate doses (500 mg/day) of vitamin C supplementation in a high-risk population for stomach cancer and stroke.
Drug Effects on Aldosterone/Plasma Renin Activity Ratio in Primary Aldosteronism
Authors: Mulatero Paolo , Rabbia Franco , Milan Alberto , Paglieri Cristina , Morello Fulvio , Chiandussi Livio , Veglio Franco
Published: December 2002

Primary aldosteronism is a specifically treatable and potentially curable form of secondary hypertension. The aldosterone/plasma renin activity ratio (ARR) is routinely used as a screening test. Antihypertensive therapy can interfere with the interpretation of this parameter, but a correct washout period can be potentially harmful. We have investigated the effects of therapy with atenolol, amlodipine, doxazosin, fosinopril, and irbesartan on the ARR in a group of 230 patients with suspected primary aldosteronism. The percent change from control of ARR in patients taking amlodipine was −17%±32; atenolol, 62%±82; doxazosin, −5%±26; fosinopril, −30%±24; and irbesartan, −43%±27. The ARR change induced by atenolol was significantly higher compared with that induced by all other drugs (
P
<0.0001), and the ARR change induced by irbesartan was significantly lower than that induced by doxazosin (
P
<0.0001). One of 55 patients from the group taking amlodipine (1.8%) and 4/17 of the patients taking irbesartan (23.5%) gave a false-negative ARR (<50). None of the patients of the groups taking fosinopril, doxazosin, and atenolol displayed a false-negative ARR. Doxazosin and fosinopril can be used in hypertensive patients who need to undergo aldosterone and PRA measurement for the diagnosis of primary aldosteronism; amlodipine gave a very small percentage of false-negative diagnoses. β-Blockers also do not interfere with the diagnosis of primary aldosteronism, but they can be responsible for an increased rate of false-positive ARRs. The high rate of false-negative diagnoses in patients undergoing irbesartan treatment requires confirmation in a higher number of patients.
Classification of Blood Pressure Levels by Ambulatory Blood Pressure in Hypertension
Authors: Bur Andreas , Herkner Harald , Vlcek Marianne , Woisetschläger Christian , Derhaschnig Ulla , Hirschl Michael M.
Published: December 2002

Whereas clinic blood pressure (CBP) above normality is divided into stages, no corresponding classifications are available for 24-hour ambulatory blood pressure (ABP). We conducted a study (1) to define stages of hypertension by ABP corresponding to CBP stages and (2) to evaluate if these stages have prognostic impact similar to CBP stages. Seven hundred thirty-six hypertensive patients were included. Mean systolic blood pressure was 149±15.2/87±8.6 mm Hg for CBP and 135±13/79±9.7 mm Hg for ABP. The mean bias between both methods was −13.3 mm Hg (95% CI, −14.3 to −12.2; 1.96×SD limits of agreement, 15.7 to −42.3) and −7.3 mm Hg (95% CI, −7.9 to −6.6; 1.96×SD limits of agreement, 9.8 to −24.3) for systolic and diastolic blood pressure (
P
>0.0001 for both), respectively. Classification of hypertension by ABP revealed lower cutoff values for the different stages of hypertension compared with the corresponding cutoff values for CBP (CBP versus ABP: 140/90 versus 132/81 mm Hg; 160/100 versus 140/88 mm Hg; 180/110 versus 148/94 mm Hg,
P
<0.001). Overall, 82 (11.1%) patients had nonfatal clinical cardiovascular events and 9 (1.2%) patients died of a cardiovascular cause during follow-up. The distribution of cardiovascular events was significantly associated with increasing ABP value (
P
<0.006). Staging of hypertension by ABP may facilitate the use of this method in daily clinical practice, as ABP can now be used not only to confirm the diagnosis of hypertension but also to assess the severity and prognosis of hypertensive disease.
Effects of Doxazosin and Propranolol on A
2A
Adenosine Receptors in Essential Hypertension
Authors: Varani Katia , Manfredini Roberto , Iannotta Valeria , Pancaldi Cecilia , Cattabriga Elena , Uluoglu Canan , Borea Pier Andrea , Portaluppi Francesco
Published: December 2002

A
2A
adenosine receptors inhibit neutrophil adhesion and superoxide anion generation. The aim of the present study was to evaluate the effect of antihypertensive treatment with doxazosin or propranolol on the binding and functional parameters of A
2A
adenosine receptors of lymphocytes and neutrophils in essential hypertensive patients. Two groups of previously untreated, essential hypertensive patients were studied. The mean affinity (K
d
) and density (B
max
) of adenosine receptors, by the A
2A
selective radioligand [
3
H]-ZM-241385 binding assays, and EC
50
, by cAMP assays, were obtained first on no medication and a second time after treatment for up to 13 weeks with doxazosin (13 patients) or propranolol (8 patients). A third group of 15 healthy normotensive volunteers matched by age, sex, and body mass index was used as a control. Binding and functional parameters of the A
2A
adenosine receptors were significantly higher in the 2 hypertensive groups than in controls (
P
always <0.0001), both in lymphocyte and neutrophil membranes. After treatment with propranolol, the binding parameters did not change significantly, whereas after treatment with doxazosin, K
d
, B
max
, and EC
50
values returned to control levels. In never-treated essential hypertensive patients, lower affinity, higher density, and impaired function of A
2A
adenosine receptors are present. The binding and functional parameters of A
2A
adenosine receptors appear to be normalized after treatment with doxazosin but not with propranolol.
Angiotensin II and Oxidative Stress in Dahl Salt-Sensitive Rat With Heart Failure
Authors: Tojo Akihiro , Onozato Maristela Lika , Kobayashi Naohiko , Goto Atsuo , Matsuoka Hiroaki , Fujita Toshiro
Published: December 2002

Reactive oxygen species have an important pathogenic role in organ damage. We investigated the role of oxidative stress via nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase in the kidney of the Dahl salt-sensitive (DS) rats with heart failure (DSHF). Eleven-week-old DS rats fed an 8%-NaCl diet received either vehicle or imidapril (1 mg/kg per day) for 7 weeks. The renal expression of the NAD(P)H oxidase p47phox and endothelial NO synthase were evaluated. In DSHF rats, associated with increased renal angiotensin II, mRNA and protein expression of NAD(P)H oxidase p47phox were enhanced with an increase in renal lipid peroxidation production (0.33±0.03 versus 0.22±0.01 nmol/mg protein,
P
<0.05) and urinary excretion of hydrogen peroxide (26.9±6.6 versus 9.5±2.1 U/mg creatinine,
P
<0.01) compared with levels in Dahl salt-resistant rats. The endothelial NO synthase expression was decreased in the kidney. Treatment with imidapril reduced renal angiotensin II and NAD(P)H oxidase expression and the oxidative products (kidney lipid peroxidation product: 0.16±0.02,
P
<0.001; urinary hydrogen peroxide: 3.1±0.2,
P
<0.01 versus DSHF rats). Imidapril significantly decreased albuminuria and reduced glomerulosclerosis without changes in the blood pressure. In conclusion, DSHF rats showed increased oxidative stress in the kidney via NAD(P)H oxidase. Blockade of local angiotensin II with subpressor dose of imidapril inhibited NAD(P)H oxidase and prevented renal damage.
Endothelin-Converting Enzyme Inhibition Ameliorates Angiotensin II–Induced Cardiac Damage
Authors: Muller Dominik N. , Mullally Alexander , Dechend Ralf , Park Joon-Keun , Fiebeler Anette , Pilz Bernhard , Löffler Bernd-Michael , Blum-Kaelin Denise , Masur Stefan , Dehmlow Henrietta , Aebi Johannes D. , Haller Hermann , Luft Friedrich C.
Published: December 2002

We tested the hypothesis that endothelin-converting enzyme (ECE) inhibition ameliorates end-organ damage in rats harboring both human renin and human angiotensinogen genes (dTGR). Hypertension develops in the animals, and they die by age 7 weeks of heart and kidney failure. Three groups were studied: dTGR (n=12) receiving vehicle, dTGR receiving ECE inhibitor (RO0687629; 30 mg/kg by gavage; n=10), and Sprague-Dawley control rats (SD; n=10) receiving vehicle, all after week 4, with euthanasia at week 7. Systolic blood pressure was not reduced by ECE inhibitor compared with dTGR (205±6 versus 206±6 mm Hg at week 7, respectively). In contrast, ECE inhibitor treatment significantly reduced mortality rate to 20% (2 of 10), whereas untreated dTGR had a 52% mortality rate (7 of 12). ECE inhibitor treatment ameliorated cardiac damage and reduced left ventricular ECE activity below SD levels. Echocardiography at week 7 showed reduced cardiac hypertrophy (4.8±0.2 versus 5.7±0.2 mg/g,
P
<0.01) and increased left ventricular cavity diameter (5.5±0.3 versus 3.1±0.1 mm,
P
<0.001) and filling volume (0.42±0.04 versus 0.16±0.06 mL,
P
<0.05) after ECE inhibitor compared with untreated dTGR. ECE inhibitor treatment also reduced cardiac fibrosis, tissue factor expression, left ventricular basic fibroblast growth factor mRNA levels, and immunostaining in the vessel wall, independent of high blood pressure. In contrast, the ECE inhibitor treatment showed no renoprotective effect. These data are the first to show that ECE inhibition reduces angiotensin II–induced cardiac damage.
Racial Difference in the Activity of the Amiloride-Sensitive Epithelial Sodium Channel
Authors: Pratt J. Howard , Ambrosius Walter T. , Agarwal Rajiv , Eckert George J. , Newman Shirley
Published: December 2002

Compared with whites, blacks appear to retain additional sodium that suppresses secretion of renin and aldosterone. The epithelial sodium channel (ENaC) is an aldosterone-regulated site for sodium reabsorption. ENaC activity could be higher in blacks, contributing to sodium retention or, alternatively, lower because of reduced stimulation by aldosterone. To examine the level of ENaC activity in blacks relative to whites, blood pressure (BP) responses to amiloride (5 mg/d), an inhibitor of ENaC, were measured in 20 black and 25 white normotensive young people. After 1 week, systolic BP decreased by 3.0±9.2 (SD) and diastolic by 2.8±8.3 mm Hg in the whites, whereas systolic BP increased by 2.5±7.1 and diastolic by 3.8±8.0 mm Hg in the blacks; the racial difference in the BP response was significant for both systolic (
P
=0.034) and diastolic BP (
P
=0.010). As ENaC activity increases, renal secretion of potassium increases proportionately, and in a larger sample of subjects, the urinary potassium excretion rate was lower in the blacks (n=301) than in the whites (n=461): 3.2±0.1 versus 3.8±0.1 mmol/mmol creatinine (
P
=0.0001). The concentration of serum potassium was higher in the blacks (n=81) than in the whites (n=167): 4.36±0.05 versus 4.21±0.03 (
P
=0.012). In summary, a favorable BP response to amiloride in the whites as well as the evidence for greater retention of potassium in the blacks is consistent with blacks having less ENaC activity than whites. We suggest that increased sodium retention in blacks occurring at other nephron sites suppresses aldosterone secretion and in turn ENaC function.
Augmented Diurnal Variations of the Cardiac Renin-Angiotensin System in Hypertensive Rats
Authors: Naito Yoshiro , Tsujino Takeshi , Fujioka Yoshio , Ohyanagi Mitsumasa , Iwasaki Tadaaki
Published: December 2002

There are several controversies concerning the enhanced gene expression of cardiac renin-angiotensin system components in spontaneously hypertensive rats (SHR) compared with their normotensive control Wistar-Kyoto (WKY) rats. We hypothesized that these discrepancies arise from circadian fluctuations in gene expression. We examined the circadian mRNA expression of renin, angiotensinogen, ACE, and angiotensin type 1a (AT1a) and type 2 (AT2) receptors in the hearts of SHR and WKY rats by real-time quantitative reverse transcription–polymerase chain reaction. The cardiac mRNA expression of the renin-angiotensin system components showed circadian oscillations in both SHR and WKY rats. The amplitudes of these circadian fluctuations were greater in the SHR than in the WKY rats. The mRNA levels of the renin-angiotensin system components were also increased in the SHR compared with the WKY rats at many time points (especially during the dark phase). However, the levels of ACE, AT1a receptor, and AT2 receptor mRNA in the SHR and WKY rats were almost the same during the late light phase. In contrast to mRNA expression, ACE activity was similar both at the time of maximum and minimum mRNA expression. The AT1 receptor antagonist candesartan upregulated AT1a receptor mRNA and downregulated ACE mRNA at specific time points only in the SHR group. Our findings of differential diurnal expression of cardiac renin-angiotensin system genes in SHR and WKY rats appear to explain the discrepancies between prior studies. However, the physiological relevance of the differential circadian mRNA expression of the renin-angiotensin system components remains to be elucidated.
Ascorbic Acid Reduces Blood Pressure and Arterial Stiffness in Type 2 Diabetes
Authors: Mullan Brian A. , Young Ian S. , Fee Howard , McCance David R.
Published: December 2002

Experimental evidence suggests that acute parenteral administration of high-dose ascorbic acid has beneficial vascular effects in type 2 diabetes. We studied the hemodynamic effects of chronic oral supplementation in this condition. Thirty patients, 45 to 70 years of age, with type 2 diabetes, were randomly assigned in a double-blind manner to receive 500 mg ascorbic acid daily by mouth or placebo. Patients were studied at baseline and after 4 weeks of assigned treatment. The central aortic augmentation index (AgIx) and the time to wave reflection (Tr) were derived from radial artery pulse wave analysis data. AgIx and Tr were used as measures of systemic arterial stiffness and aortic stiffness, respectively. Ascorbic acid decreased brachial systolic blood pressure from 142.1±12.6 (SD) to 132.3±12.1 mm Hg (difference [95% CI] 9.9 [4.7, 15.0];
P
<0.01), brachial diastolic pressure from 83.9±4.8 to 79.5±6.0 mm Hg (4.4 [1.8, 7.0];
P
<0.01), and AgIx from 26.8±5.5% to 22.5±6.8% (4.3 [1.5, 7.1];
P
<0.01). Tr increased from 137.1±12.6 to 143.4±9.2 ms (−6.3 [−10.1, −2.5];
P
<0.01). Placebo had no hemodynamic effects, and this difference between treatments was significant (
P
<0.01 for blood pressure and Tr,
P
=0.03 for AgIx). We have therefore shown that after 1 month, oral ascorbic acid lowered arterial blood pressure and improved arterial stiffness in patients with type 2 diabetes. As strict control of blood pressure reduces cardiovascular risk in diabetes, ascorbic acid supplementation may potentially be a useful and inexpensive adjunctive therapy. Larger and longer studies now need to be performed.
Serum Antioxidant Vitamins and Blood Pressure in the United States Population
Authors: Chen Jing , He Jiang , Hamm Lee , Batuman Vecihi , Whelton Paul K.
Published: December 2002

Serum vitamin C has been inversely associated with blood pressure in several epidemiologic studies, but little is known about effect of other antioxidant vitamins. We examined the relation between serum vitamins A, C, and E, α-carotene, and β-carotene levels and blood pressure among 15 317 men and women ≥20 years of age who participated in the Third National Health and Nutrition Examination Survey. Blood pressure was characterized as the average of 6 measurements obtained over 2 visits by trained observers and hypertension was defined as blood pressure ≥140/90 mm Hg and/or taking antihypertensive medications. In multivariate models, a 1 SD difference in vitamin A (16.2 μg/dL) and vitamin E (20.4 μg/dL) was associated with a 43% (OR, 1.43; 95% CI, 1.34 to 1.53) and 18% (OR, 1.18; 95% CI, 1.09 to 1.27) higher odds of hypertension, respectively. A 1 SD difference in α-carotene (0.47 μg/dL) and β-carotene (496 μg/dL) was associated with a 16% (OR, 0.84; 95% CI, 0.76 to 0.94) and 11% (OR, 0.89; 95% CI, 0.82 to 0.97) lower odds of hypertension, respectively. In addition, serum vitamins A and E were positively and significantly associated with both systolic and diastolic blood pressure, whereas α-carotene and β-carotene were inversely and significantly associated with systolic and vitamin C associated with diastolic blood pressure in multivariate linear regression analyses. These findings indicate that antioxidant vitamins may be important in the underlying cause and prevention of hypertension. Further studies in this important area are warranted.
Rosiglitazone Treatment Restores Renal Dopamine Receptor Function in Obese Zucker Rats
Authors: Umrani Dhananjay N. , Banday Anees A. , Hussain Tahir , Lokhandwala Mustafa F.
Published: December 2002

Earlier we have reported a defective dopamine D
1
–like receptor function, which was accompanied by a decrease in D1 receptor numbers and the inability of dopamine to inhibit Na,K-ATPase and Na,H-exchanger in proximal tubules of hyperinsulinemic obese Zucker rats. The present study was designed to test the hypothesis that the defect in dopamine receptor function is a result of hyperinsulinemia in obese rats. We designed experiments to study D1 receptor function in obese Zucker rats treated with rosiglitazone, as it lowers plasma insulin by improving insulin sensitivity. A group of untreated lean and obese rats served as controls. Rosiglitazone treatment (10 mg/kg orally, 4 weeks) caused significant decreases in plasma insulin, blood glucose, and blood pressure while causing an increase in renal sodium excretion compared with untreated obese rats. In the isolated proximal tubules obtained from untreated lean rats, dopamine caused concentration-dependent inhibition of the Na,K-ATPase activity, but this inhibitory effect was absent in untreated obese rats. In rosiglitazone-treated obese rats, the inhibitory effect of dopamine on Na,K-ATPase was significantly restored. This was accompanied by a complete restoration of D1 receptor numbers in proximal tubular membranes of treated obese rats. In another set of experiments, treatment of primary proximal tubule epithelial cells in culture medium with insulin caused a significant decrease in the D1 receptor abundance, suggesting a direct role of insulin on D1 receptor regulation. We conclude that hyperinsulinemia causes downregulation of D1 receptor function and lowering of plasma insulin levels leads to restoration of renal D1 receptor function.
Hyperaldosteronism Among Black and White Subjects With Resistant Hypertension
Authors: Calhoun David A. , Nishizaka Mari K. , Zaman Mohammad A. , Thakkar Roopal B. , Weissmann Paula
Published: December 2002

Recent reports suggesting that the prevalence of primary hyperaldosteronism may be higher than historically thought have relied on an elevated plasma aldosterone concentration/plasma renin activity ratio to either diagnose or identify subjects at high risk of having primary hyperaldosteronism and have not included suppression testing of all evaluated subjects. In this prospective study of 88 consecutive patients referred to a university clinic for resistant hypertension, we determined the 24-hour urinary aldosterone excretion during high dietary salt ingestion, baseline plasma renin activity, and plasma aldosterone in all subjects. Primary hyperaldosteronism was confirmed if plasma renin activity was <1.0 ng/mL per hour and urinary aldosterone was >12 μg/24-hour during high urinary sodium excretion (>200 mEq/24-hour). Eighteen subjects (20%) were confirmed to have primary hyperaldosteronism. The prevalence of hyperaldosteronism was similar in black and white subjects. Of the 14 subjects with confirmed hyperaldosteronism who have been treated with spironolactone, all have manifested a significant reduction in blood pressure. In this population, an elevated plasma aldosterone/plasma renin activity ratio (>20) had a sensitivity of 89% and a specificity of 71% with a corresponding positive predictive value of 44% and a negative predictive value of 96%. These data provide strong evidence that hyperaldosteronism is a common cause of resistant hypertension in black and white subjects. The accuracy of these results is strengthened by having done suppression testing of all evaluated subjects.
Angiotensin II–Induced Insulin Resistance Is Associated With Enhanced Insulin Signaling
Authors: Ogihara Takehide , Asano Tomoichiro , Ando Katsuyuki , Chiba Yuko , Sakoda Hideyuki , Anai Motonobu , Shojima Nobuhiro , Ono Hiraku , Onishi Yukiko , Fujishiro Midori , Katagiri Hideki , Fukushima Yasushi , Kikuchi Masatoshi , Noguchi Noriko , Aburatani Hiroyuki , Komuro Issei , Fujita Toshiro
Published: December 2002

Angiotensin II (AII) is involved in the pathogenesis of both hypertension and insulin resistance, though few studies have examined the relationship between the two. We therefore investigated the effects of chronic AII infusion on blood pressure and insulin sensitivity in rats fed a normal (0.3% NaCl) or high-salt (8% NaCl) diet. AII infusion for 12 days significantly elevated blood pressure and significant insulin resistance, assessed by a hyperinsulinemic-euglycemic clamp study and glucose uptake into isolated muscle and adipocytes. High-salt loading exacerbated the effects of AII infusion significantly. Despite the insulin resistance, insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrates, activation of phosphatidylinositol (PI) 3-kinase, and phosphorylation of Akt were all enhanced by AII infusion. Subsequently, to investigate whether oxidative stress induced by AII contributes to insulin resistance, the membrane-permeable superoxide dismutase mimetic, tempol, was administered to AII-infused rats. Chronic AII infusion induced an accumulated plasma cholesterylester hydroperoxide levels, indicating the increased oxidative stress, whereas the treatment with tempol normalized plasma cholesterylester hydroperoxide levels in AII-infused rats. In addition, the treatment with tempol normalized insulin resistance in AII-infused rats, shown as a decreased glucose infusion rate in the hyperinsulinemic euglycemic clamp study and a decreased insulin-induced glucose uptake into isolated skeletal muscle, as well as enhanced insulin-induced PI 3-kinase activation to those in the control rats. These results strongly suggest that AII-induced insulin resistance cannot be attributed to impairment of early insulin-signaling steps and that increased oxidative stress, possibly through impaired insulin signaling located downstream from PI 3-kinase activation, is involved in AII-induced insulin resistance.
Prevalence, Awareness, Treatment, and Control of Hypertension in China
Authors: Gu Dongfeng , Reynolds Kristi , Wu Xigui , Chen Jing , Duan Xiufang , Muntner Paul , Huang Guanyong , Reynolds Robert F. , Su Shaoyong , Whelton Paul K. , He Jiang
Published: December 2002

The objective of this study was to estimate the prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment, and control in the general adult population in China. The International Collaborative Study of Cardiovascular Disease in ASIA (InterASIA), conducted in 2000–2001, used a multistage cluster sampling method to select a nationally representative sample. A total of 15 540 adults, age 35 to 74 years, were examined. Three blood pressure measurements were obtained by trained observers by use of a standardized mercury sphygmomanometer after a 5-minute sitting rest. Information on history of hypertension and use of antihypertensive medications was obtained by use of a standard questionnaire. Hypertension was defined as a mean systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, and/or use of antihypertensive medications. Overall, 27.2% of the Chinese adult population age 35 to 74 years, representing 129 824 000 persons, had hypertension. The age-specific prevalence of hypertension was 17.4%, 28.2%, 40.7%, and 47.3% in men and 10.7%, 26.8%, 38.9%, and 50.2% in women age 35 to 44 years, 45 to 54 years, 55 to 64 years, and 65 to 74 years, respectively. Among hypertensive patients, only 44.7% were aware of their high blood pressure, 28.2% were taking antihypertensive medication, and 8.1% achieved blood pressure control (<140/90 mm Hg). Our results indicate that hypertension is highly prevalent in China. The percentages of those with hypertension who are aware, treated, and controlled are unacceptably low. These results underscore the urgent need to develop national strategies to improve prevention, detection, and treatment of hypertension in China.