Nitrite represents a bioactive reservoir of nitric oxide (NO) that may modulate vasodilation, respiration and cytoprotection after ischemia-reperfusion injury. Although nitrite formation is thought to occur via reaction of NO with oxygen, this third-order reaction cannot compete kinetically with the reaction of NO with hemoglobin to form nitrate. Indeed, the formation of nitrite from NO in the blood is limited when plasma is substituted with physiological buffers, which suggests that plasma contains metal-based enzymatic pathways for nitrite synthesis. We therefore hypothesized that the multicopper oxidase, ceruloplasmin, could oxidize NO to NO+, with subsequent hydration to nitrite. Accordingly, plasma NO oxidase activity was decreased after ceruloplasmin immunodepletion, in ceruloplasmin knockout mice and in people with congenital aceruloplasminemia. Compared to controls, plasma nitrite concentrations were substantially reduced in ceruloplasmin knockout mice, which were more susceptible to liver infarction after ischemia and reperfusion. The extent of hepatocellular infarction normalized after nitrite repletion. These data suggest new functions for the multicopper oxidases in endocrine NO homeostasis and nitrite synthesis, and they support the hypothesis that physiological concentrations of nitrite contribute to hypoxic signaling and cytoprotection.

Cardiac rehabilitation in patients receiving stable statin therapy and with low-density lipoprotein cholesterol at goal increases EPC number, EPC survival, and endothelial differentiation potential, associated with increased nitric oxide in the blood. Although this response was observed in most patients, a significant minority showed neither EPC mobilization nor increased nitric oxide in the blood.

Background Digital tonometry is designed to noninvasively screen for endothelial dysfunction by the detection of impaired flow-induced reactive hyperemia in the fingertip. We determined whether digital reactive hyperemia correlated with risk factors for atherosclerosis in 2 groups of children at increased risk for endothelial dysfunction. Methods Fifteen obese children and 23 non-obese, dyslipidemic children, 8-21 years of age, were enrolled and medical histories, anthropometric measurements, carotid wall thickness by ultrasound and fasting blood samples for cardiovascular risk factors were obtained. The standard endoPAT index of digital reactive hyperemia was modified to reflect the true peak response or the integrated response of the entire post-occlusion period. In each group, age, sex, pubertal status, carotid wall thickness and multiple cardiovascular risk factors were tested as predictors of endothelial dysfunction. Results In the nonobese, dyslipidemic group, but not the obese group, both indices strongly correlated with height (r=0.55, P=0.007 by peak response) followed by weight, waist circumference and age. In both groups, neither index of reactive hyperemia significantly correlated with any other cardiovascular risk factor. Conclusions Contrary to the known age-related increase in atherosclerosis, digital reactive hyperemia increased with age and its correlates in nonobese, dyslipidemic children and was not related to other cardiovascular risk factors in either group. The reason for the lack of this relationship with age in obese children is unknown. The age-dependent physiology of digital microvascular reactivity and the endothelium-independent factors controlling the peak hyperemic response need further study in children with a wide age range.

SUMMARYTo determine if there was an association between recto-vaginal group B streptococcus (GBS) colonization and pre-eclampsia, two cross-sectional studies were conducted using statewide hospital databases. The first study analysed data from the state of Florida, USA, and included 190 645 women who were discharged in 2001. This dataset was used to generate the hypothesis that GBS colonization is associated with pre-eclampsia. The second study tested the GBS hypothesis using the records of 577 153 women who delivered in 2004 or 2005 in Texas, USA. Adjusted odds ratios (aOR) for the outcome of pre-eclampsia comparing GBS-positive to GBS-negative women were calculated using logistic regression. The aOR for the association between GBS carriage and pre-eclampsia was 0·71 [95% confidence interval (CI) 0·65–0·77] in the Florida dataset. In the Texas dataset, the overall prevalence of GBS carriage was 14·1% while the overall prevalence of pre-eclampsia was 4·0%. GBS carriers were 31% less likely than non-carriers to have pre-eclampsia (aOR 0·69, 95% CI 0·66–0·72) in Texas. In two large statewide analyses, GBS carriage was inversely associated with pre-eclampsia. A sensitivity analysis revealed that misclassification of GBS status is not a likely explanation of our findings.