No evidence of endothelial dysfunction in patients with Alzheimer's disease

In view of accumulating evidence of vascular pathology in Alzheimer's disease (AD), we tested the hypothesis that AD patients have impaired endothelial function. This was assessed using the technique of strain-gauge venous occlusion plethysmography, which measures forearm blood flow (FBF). Intra-arterial (brachial) infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) was used to assess local endothelial dependent and independent responses, respectively. There was no difference in the basal FBF of patients and controls. ACh and SNP caused dose-related increases in FBF from baseline, but no difference was recorded between the AD and control group. This study provides no evidence of endothelial dysfunction in the systemic circulation of patients with AD.

Microcirculatory hemodynamics and endothelial dysfunction in systemic lupus erythematosus.

OBJECTIVE: Impaired flow-mediated dilation (FMD) occurs in disease states associated with atherosclerosis, including SLE. The primary hemodynamic determinant of FMD is wall shear stress, which is critically dependent on the forearm microcirculation. We explored the relationship between FMD, diastolic shear stress (DSS), and the forearm microcirculation in 32 patients with SLE and 19 controls. METHODS AND RESULTS: DSS was calculated using (mean diastolic velocity x 8 x blood viscosity)/baseline brachial artery diameter. Doppler velocity envelopes from the first 15 seconds of reactive hyperemia were analyzed for resistive index (RI), and interrogated in the frequency domain to assess forearm microvascular hemodynamics. FMD was significantly impaired in SLE patients (median, 2.4%; range, -2.1% to 10.7% versus median 5.8%; range, 1.9% to 14%; P

Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC cohort and their relationship with nephropathy and macrovascular complications

Because endothelial cell dysfunction and inflammation are key contributors to the development of complications in type 1 diabetes, we studied risk factors related to endothelial dysfunction and inflammation (C-reactive protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin, and fibrinolytic markers) in a subgroup of patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study cohort.

A lethal tetrad in diabetes:hyperglycemia, dyslipidemia, oxidative stress, and endothelial dysfunction

This paper addresses the consequences of diabetes and obesity, diseases that have become epidemic in our society, particularly in the past 20 years. Specifically, it summarizes current knowledge about some of the risk factors and mechanisms for the vascular complications of diabetes. These complications can be broadly divided into microvascular disease, such as diabetic retinopathy and diabetic nephropathy, and macrovascular disease, such as accelerated atherosclerosis, and they are the main cause for morbidity and premature mortality among diabetic patients. The roles of hyperglycemia, dyslipidemia and dyslipoproteinemia, oxidative stress, and endothelial dysfunction will be considered. Finally, the "treatment gap" will be addressed. This gap refers to our failure to achieve currently accepted goals to reduce established risk factors for complications in the clinical management of diabetic patients.

Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation

Objective: Enhanced oxidative stress is involved in mediating the endothelial dysfunction associated with hypertension. The aim of this study was to investigate the relative contributions of pro-oxidant and anti-oxidant enzymes to the pathogenesis of endothelial dysfunction in genetic hypertension. Methods: Dilator responses to endothelium-dependent and endothelium-independent agents such as acetylcholine (ACh) and sodium nitroprusside were measured in the thoracic aortas of 28-week-old spontaneously hypertensive rats (SHR) and their matched normotensive counterparts, Wistar Kyoto rats (WKY). The activity and expression (mRNA and protein levels) of endothelial nitric oxide synthase (eNOS), p22-phox, a membrane-bound component of NAD(P)H oxidase, and antioxidant enzymes, namely, superoxide dismutases (CuZn- and Mn-SOD), catalase and glutathione peroxidase (GPx), were also investigated in aortic rings. Results: Relaxant responses to ACh were attenuated in phenylephrine-precontracted SHR aortic rings, despite a 2-fold increase in eNOS expression and activity. Although the activity and/or expression of SODs, NAD(P)H oxidase (p22-phox) and GPx were elevated in SHR aorta, catalase activity and expression remained unchanged compared to WKY. Pretreatment of SHR aortic rings with the inhibitor of xanthine oxidase, allopurinol, and the inhibitor of cyclooxygenase, indomethacin, significantly potentiated ACh-induced relaxation. Pretreatment of SHR rings with catalase and Tiron, a superoxide anion (O) scavenger, increased the relaxant responses to the levels observed in WKY rings whereas pyrogallol, a O -generator, abolished relaxant responses to ACh. Conclusion: These data demonstrate that dysregulation of several enzymes, resulting in oxidative stress, contributes to the pathogenesis of endothelial dysfunction in SHR and indicate that the antioxidant enzyme catalase is of particular importance in the reversal of this defect. © 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.