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Stressors contribute to thrombosis and insulin resistance. Since obesity-related adipose inflammation is also involved in these pathological states, we assumed that stress correlates with adipose inflammation. Male mice were subjected to 2-week intermittent restraint stress. Expression of plasma lipids, monocyte/macrophage markers (CD11b, CD68, and F4/80), proinflammatory cytokines (monocyte chemoattractant protein-1 [MCP-1], tumor necrosis factor-α, and interleukin-6), adiponectin, heat shock protein 70.1 (HSP70.1), and coagulation factors (plasminogen activation inhibitor-1 [PAI-1] and tissue factor [TF]) in blood and inguinal white adipose tissue (WAT) was determined using immunohistochemistry, enzyme-linked immunosorbent assay, and RT-PCR, respectively. Glucose metabolism was assessed by glucose tolerance tests (GTTs) and insulin tolerance tests, and expression of insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) in WAT. To examine effects of MCP-1 blockade, animals were treated with control or neutralizing antibody, or transplanted with control or 7ND (dominant-negative form of MCP-1)-overexpressing adipose-derived stromal cells (ADSCs). Stress increased monocyte accumulation, free fatty acids, proinflammatory cytokine, and HSP70.1 and reduced adiponectin. Adipose stromal cells highly expressed MCP-1. The stress-induced adipose inflammation increased PAI-1 and TF but did not give rise to thrombus formation. Without any changes in GTT, stress worsened insulin sensitivity and decreased IRS-1 and GLUT4 in WAT. Neutralizing antibody and 7ND-ADSCs reversed stress-induced adipose inflammation, procoagulant state, and insulin resistance. Stress evoked adipose inflammation to increase coagulation factors and impair insulin sensitivity through adipose-derived MCP-1. [ABSTRACT FROM AUTHOR]

Although recent clinical trials have found an increased incidence of cardiovascular disease in women on estrogen replacement therapy, the underlying mechanism remains unclear. We have recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome. We have now examined the effects of estrogen replacement on cardiac pathophysiology in ovariectomized female DS/obese (Ovx-DS/obese) rats. Animals subjected to ovariectomy at 7 weeks of age were implanted subcutaneously with a 60-day release pellet containing 0.5 mg of 17β-estradiol (E(2)) or placebo at 8 weeks. Age-matched female homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+) or DS/lean rats) of DS/obese rats served as controls. Animals were maintained on a normal diet and were subjected to echocardiography followed by various pathological analyses at 13 weeks of age. Ovx-DS/obese rats manifested hypertension at 7 weeks of age and thereafter and showed left ventricular (LV) fibrosis and diastolic dysfunction at 13 weeks. Treatment with E(2) attenuated hypertension in Ovx-DS/obese rats but had no effect on blood pressure in ovariectomized female DS/lean (Ovx-DS/lean) rats. E(2) treatment exacerbated LV fibrosis and diastolic dysfunction, as well as further increased cardiac oxidative stress and inflammation in Ovx-DS/obese rats, and it elicited similar effects in Ovx-DS/lean rats. E(2) reduced food intake, body weight, and visceral fat content in both Ovx-DS/obese and Ovx-DS/lean rats. E(2) treatment attenuated hypertension and obesity but exacerbated LV fibrosis and diastolic dysfunction in Ovx-DS/obese rats, with these latter effects being associated with increased cardiac oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

It has not been fully examined whether angiotensin II receptor blocker is superior to calcium channel blocker to reduce cardiovascular events in hypertensive patients with glucose intolerance. A prospective, open-labeled, randomized, controlled trial was conducted for Japanese hypertensive patients with type 2 diabetes mellitus or impaired glucose tolerance. A total of 1150 patients (women: 34%; mean age: 63 years; diabetes mellitus: 82%) were randomly assigned to receive either valsartan- or amlodipine-based antihypertensive treatment. Primary outcome was a composite of acute myocardial infarction, stroke, coronary revascularization, admission attributed to heart failure, or sudden cardiac death. Blood pressure was 145/82 and 144/81 mm Hg, and glycosylated hemoglobin was 7.0% and 6.9% at baseline in the valsartan group and the amlodipine group, respectively. Both of them were equally controlled between the 2 groups during the study. The median follow-up period was 3.2 years, and primary outcome had occurred in 54 patients in the valsartan group and 56 in the amlodipine group (hazard ratio: 0.97 [95% CI: 0.66-1.40]; P=0.85). Patients in the valsartan group had a significantly lower incidence of heart failure than in the amlodipine group (hazard ratio: 0.20 [95% CI: 0.06-0.69]; P=0.01). Other components and all-cause mortality were not significantly different between the 2 groups. Composite cardiovascular outcomes were comparable between the valsartan- and amlodipine-based treatments in Japanese hypertensive patients with glucose intolerance. Admission because of heart failure was significantly less in the valsartan group. [ABSTRACT FROM AUTHOR]

BACKGROUND: The biologic response to angiotensin-converting enzyme (ACE) inhibitors may be influenced by the local environment. The effect of ACE inhibition on coronary angiogenesis was investigated in a rat model of hypertensive heart failure. METHODS AND RESULTS: Dahl salt-sensitive (DS) rats fed a high-salt diet from 6 weeks of age were treated with a nonantihypertensive dose of the ACE inhibitor perindopril or vehicle from 9 to 18 weeks. Treatment of rats with perindopril attenuated the heart failure as well as cardiac hypertrophy and fibrosis that were manifest in the vehicle-treated animals. Myocardial capillary density as well as the expression of the bradykinin B(2) receptor, endothelial nitric oxide synthase, and vascular endothelial growth factor were reduced in the heart of vehicle-treated rats compared with that of nonhypertensive control rats, and all of these changes were attenuated by treatment with perindopril. CONCLUSIONS: These results indicate that ACE inhibition by perindopril promotes myocardial capillary formation as well as attenuates cardiac remodeling and failure in a manner independent from the antihypertensive effect of the drug in DS hypertensive rats. The beneficial cardiac effects of perindopril were associated with activation of the bradykinin-nitric oxide pathway in the heart. [ABSTRACT FROM AUTHOR]

A 66-year-old woman with idiopathic premature ventricular contractions with a left bundle branch block QRS morphology and left inferior axis underwent electrophysiologic testing. Successful radiofrequency ablation was achieved in the right coronary cusp (RCC). However, radiofrequency ablation at sites adjacent to the successful ablation site provoked sinus bradycardia followed by atrioventricular conduction block. That phenomenon might be explained by a vagal reflex through stimulation of vagal pathways or receptors in the anterior epicardial fat pads neighboring to the RCC. A vagal reflex should be kept in mind as a complication during catheter ablation of ventricular arrhythmias originating from the RCC. [ABSTRACT FROM AUTHOR]

The renin-angiotensin system (RAS) plays an important role in the maintenance of normal blood pressure and the etiology of hypertension; however, minimal attention has been paid to the degradation of the effector peptide, angiotensin II (AngII). Since aminopeptidase A (APA)-deficient mice develop hypertension APA appears to be an essential enzyme in the control of blood pressure via degradation of AngII. The robust hypertension seen in the spontaneously hypertensive rat (SHR) is due to activation of the RAS, and an accompanying decrease in kidney APA. Changes in APA have also been measured during the activation of the RAS in the Goldblatt hypertension model and Dahl salt-sensitive (DSS) rat. The DSS rat shows an elevation in renal APA activity at the onset of hypertension suggesting a protective role against elevations in circulating AngII, followed by decreased APA activity with advancing hypertension. Changes seen in human maternal serum APA activity during preeclampsia are similar to changes measured in renal APA in the DSS rat model. APA activity is higher than during normal pregnancy at the onset of preeclampsia, and with advancing preeclampsia (severe preeclampsia) declines below that seen during normal pregnancy. Serum APA activity is also increased during hormone replacement therapy (HRT), perhaps in reaction to elevated levels of AngII. Thus, it appears important to consider the relationship among activation of the RAS, circulating levels of AngII, and the availability of APA in hypertensive disorders. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The right pulmonary veins (RPVs) and posterior wall of the right atrium (PRA) are anatomically located adjacent to each other. The aim of this study was to demonstrate the electrophysiologic characteristics of atrial tachycardia (AT) originating from the PRA or RPVs. METHODS AND RESULTS: A total of 26 consecutive patients with AT originating from the RPVs or PRA underwent detailed atrial endocardial mapping and successful radiofrequency catheter ablation. Eight foci were found in the PRA and 18 foci in the RPVs. Analysis of P wave configuration showed that lead V1 was the most helpful in distinguishing the AT foci between these two sites. In all cases, double potential (DP) configurations were recorded from several electrodes of a multielectrode catheter placed in the PRA, and the first DP component (FP) was the earliest potential recorded from the right atrium during the tachycardia. The amplitude of the FP was higher than that of the second DP component (SP) for AT foci originating in the PRA, whereas the reverse occurred for those in the RPV. The activation sequence of the FP was from superior to inferior for the AT foci in the superior RPV, whereas the reverse occurred for the AT foci in the inferior RPV. CONCLUSION: P wave configuration in lead V1 is helpful in distinguishing AT foci between those originating in the PRA and RPVs. The DPs obtained from the PRA can be useful in predicting whether AT foci originate from the PRA or RPVs. [ABSTRACT FROM AUTHOR]

Aims Dispersion of ventricular depolarization-repolarization in 12-lead electrocardiograms (ECGs) has been reported to provide noninvasive information on arrhythmogenicity. However, there are two methods to calculate the dispersion from ECGs including and excluding limb leads. The aim of this study was to examine whether temporal parameters from limb leads represent activation and repolarization of a particular part of the body surface. Methods and Results We compared the temporal parameters of activation time (AT), activation-recovery interval (ARI), and recovery time (RT) from limb leads of ECGs with those from an 87-lead body surface maps. The study population consisted of 50 normal subjects (25 men and 25 women, 19·4±1·6 years). The temporal parameters in leads I, II, and III were highly (r>0·9) correlated with those in unipolar leads over the left lateral, left lower, and right lower chest, respectively. The temporal parameters in leads aVR, aVL, and aVF showed a significant correlation (r>0·8) with those in unipolar leads over the right upper, left upper, and lower anterior chest, respectively. The mean AT, ARI, and RT from each limb lead of ECG were almost the same as those of unipolar leads over the corresponding areas of the body surface. Conclusions These findings suggest that ATs, ARIs, and RTs from limb leads may represent those from unipolar leads of particular areas over the body surface in normal subjects. The temporal parameters from limb leads of ECGs may provide information on activation and repolarization as well as the precordial leads of ECGs. [ABSTRACT FROM PUBLISHER]