Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol.

Endothelial dysfunction is more prevalent in African Americans (AAs) compared with whites. The authors hypothesized that nebivolol, a selective ß1 -antagonist that stimulates nitric oxide (NO), will improve endothelial function in AAs with hypertension when compared with metoprolol. In a double-blind, randomized, crossover study, 19 AA hypertensive patients were randomized to a 12-week treatment period with either nebivolol 10 mg or metoprolol succinate 100 mg daily. Forearm blood flow (FBF) was measured using plethysmography at rest and after intra-arterial infusion of acetylcholine and sodium nitroprusside to estimate endothelium-dependent and independent vasodilation, respectively. Physiologic vasodilation was assessed during hand-grip exercise. Measurements were repeated after NO blockade with L-N(G) -monomethylarginine (L-NMMA) and after inhibition of endothelium-derived hyperpolarizing factor (EDHF) with tetraethylammonium chloride (TEA). NO blockade with L-NMMA produced a trend toward greater vasoconstriction during nebivolol compared with metoprolol treatment (21% vs 12% reduction in FBF, P=.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (P<.001). Similarly, there was a contribution of NO to exercise-induced vasodilation during nebivolol but not during metoprolol treatment. There were significantly greater contributions of NO and EDHF to resting vasodilator tone and of NO to exercise-induced vasodilation with nebivolol compared with metoprolol in AAs with hypertension.

Insufficient nitric oxide bioavailability: a hypothesis to explain adverse effects of red blood cell transfusion.

While transfusion of red blood cells (RBCs) is effective at preventing morbidity and mortality in anemic patients, studies have indicated that some RBC components have functional defects ("RBC storage lesions") that may actually cause adverse events when transfused. For example, in some studies patients transfused with RBCs stored more than 14 days have had statistically worse outcomes than those receiving "fresher" RBC units. Recipient-specific factors may also contribute to the occurrence of these adverse events. Unfortunately, these events have been difficult to investigate because up to now they have existed primarily as "statistical occurrences" of increased morbidity and mortality in large data sets. There are currently no clinical or laboratory methods to detect or study them in individual transfusion recipients. We propose a unifying hypothesis, centered on insufficient nitric oxide bioavailability (INOBA), to explain the increased morbidity and mortality observed in some patients after RBC transfusion. In this model, variables associated with RBC units (storage time; 2,3-diphosphoglycerate acid concentration) and transfusion recipients (endothelial dysfunction) collectively lead to changes in nitric oxide (NO) levels in vascular beds. Under certain circumstances, these variables are "aligned" such that NO concentrations are markedly reduced, leading to vasoconstriction, decreased local blood flow, and insufficient O(2) delivery to end organs. Under these circumstances, the likelihood of morbidity and mortality escalates. If the key tenets of the INOBA hypothesis are confirmed, it may lead to improved transfusion methods including altered RBC storage and/or processing conditions, novel transfusion recipient screening methods, and improved RBC-recipient matching.

Oxidative stress markers are associated with persistent atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) has been associated with myocardial oxidative stress, and antioxidant agents have demonstrated antiarrhythmic benefit in humans. We compared serum markers of oxidation and associated inflammation in individuals with or without AF. METHODS: Serum markers of oxidative stress and inflammation were compared in a cross-sectional, case-control design study of 40 male individuals, with or without persistent or permanent AF, who were matched for age, sex, diabetes, and smoking status, known confounding variables for the measurement of oxidative stress. We used derivatives of reactive oxidative metabolites (DROMs) and ratios of oxidized to reduced glutathione (E(h) GSH) and cysteine (E(h) CySH) to quantify oxidative stress. We also measured inflammatory markers, including high-sensitivity C-reactive protein, interleukins 1beta and 6, and tumor necrosis factor alpha. RESULTS: Univariate, conditional logistical regression analysis showed that oxidative stress but not inflammatory markers were statistically associated with AF (P <0.05). The increase in the odds ratios for AF for E(h) GSH, E(h) CySH, and DROMs were 6.1 (95% CI, 1.3-28.3; P = 0.02), 13.6 (95% CI, 2.5-74.1; P = 0.01), and 15.9 (95% CI, 1.7-153.9; P = 0.02), respectively. There was a stronger correlation between E(h) GSH and E(h) CySH (r = 0.66) than between E(h) GSH and DROMs (r = 0.41). In multivariate analysis corrected for statins and other AF risk factors differing between the groups, the association of AF and oxidative stress remained significant. CONCLUSIONS: These data suggest that oxidative stress markers may have predictive value in AF management.