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Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo- controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium- dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium- dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus. [ABSTRACT FROM AUTHOR]

Epidemiological studies indicate that moderate ethanol consumption reduces cardiovascular mortality. Cellular and animal data suggest that ethanol confers beneficial effects on the vascular endothelium and increases the bioavailability of nitric oxide. The purpose of this study was to assess the effect of ethanol on endothelium-dependent, nitric oxide-mediated vasodilation in healthy human subjects. Forearm blood flow (FBF) was determined by venous occlusion plethysmography in healthy human subjects during intra-arterial infusions of either methacholine (0.3, 1.0, 3.0, and 10.0 mcg/min, n = 9), nitropmsside (0.3, 1.0, 3.0, and 10.0 mcg/min, n = 9), or verapamil (10, 30, 100, and 300 mcg/min, n = 8) before and during the concomitant intra-arterial infusions of ethanol (10% ethanol in 5% dextrose). Additionally, a time control experiment was conducted, during which the methacholine dose-response curve was measured twice during vehicle infusions (n = 5). During ethanol infusion, mean forearm and systemic alcohol levels were 227 - 30 and 6 ± 0 mg/dl, respectively. Ethanol infusion alone reduced FBF (2.5 ± 0.1 to 1.9 ± 0.1 ml·dl-1·min-1, P < 0.05). Despite initial vasoconstriction, ethanol augmented the FBF dose-response curves to methacholine, nitropmsside, and verapamil (P < 0.01 by ANOVA for each). To determine whether this augmented FBF response was related to shear-stress-induced release of nitric oxide, FBF was measured during the coinfusion of ethanol and NG-nitro-L-arginine (1-NAME; n = 8) at rest and during verapamilinduced vasodilation. The addition of L-NAME did not block the ability of ethanol to augment verapamil-induced vasodilation. Ethanol has complex direct vascular effects, which include basal vasoconstriction as well as potentiation of both endothelium-dependent and -independent vasodilation. None of these effects appear to be mediated by an increase in nitric oxide bioavailability, thus disputing findings from preclinical models. [ABSTRACT FROM AUTHOR]

Oxidative stress decreases the bioavailability of endothelium-derived nitric oxide in diabetic patients. We investigated whether impaired endothelium-dependent vasodilation (EDV) in diabetes can be improved by long-term administration of oral antioxidants. Forty-nine diabetic subjects [26 Type 1 (T1) and 23 Type 2 (T2)] and 45 matched healthy control subjects were randomized to receive oral vitamin C (1,000 mg) and vitamin E (800 IU) daily or matching placebo for 6 mo. Vascular ultrasonography was used to determine brachial artery EDV and endothelium-independent vasodilation (EIV). EDV was decreased in both T1 (4.9 ± 0.9%, P = 0.015) and T2 (4.1 ± 1.0%, P < 0.01) subjects compared with control subjects (7.7 ± 0.7%). EIV was decreased in T2 (15.0 ± 1.2%, P < 0.01) but not T1 subjects (18.5 ± 2.3%, P = 0.3) compared with controls (21.8 ± 1.8%). Administration of antioxidant vitamins increased EDV in T1 (by 3.4 ± 1.4%, P = 0.023) but not T2 subjects (by 0.5. ± 0.4%, P = 0.3). Antioxidant therapy had no significant affect on EIV. Oral antioxidant therapy improves EDV in T1 but not T2 diabetes. These results are consistent with the lack of clinical benefit in studies that have included primarily T2 diabetic patients. [ABSTRACT FROM AUTHOR]

Examines the role of angiotensin II the compliance of artery in congestive heart failure. Increase in the carotid artery compliance during isobaric conditions; Positive association of angiotensin II with congestive heart failure; Improvement on left ventricular performance in patients with heart failure.

Presents information on a study that examined the hemodynamic effects of BQ-123, an endothelin type A receptor antagonist on healthy volunteers exposed to normoxia and hypoxia. Methodology of the study; Results and discussion on the study.

Presents information on a study which examined endothelial function during stimulation of the renin-angiotensin system, and the role of angiotensin II receptor blockade in the function. Methodology; Results of the study; Discussion.