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Abstract-Environmental tobacco smoke (ETS) acutely affects peripheral and coronary vascular tone. Whether ETS exerts specific deleterious effects on aortic wave reflection through nicotine exposure, whether they persist after ETS cessation, and whether the smoke environment impairs microvascular function and increases asymmetrical dimethyl-arginine levels are not known. We tested these hypotheses in a randomized, crossover study design in 11 healthy male nonsmokers. The effects of 1 hour of exposure to ETS, as compared with a nontobacco smoke and normal air, on augmentation index corrected for heart rate and skin microvascular hyperemia to local heating were examined. Augmentation index increased both during (Pϭ0.01) and after (PϽ0.01) the ETS session but remained unchanged in the nontobacco smoke session when compared with normal air. Nicotine levels after the exposure were related to the peak rise in augmentation index (rϭ0.84; PϽ0.01), denoting a predominant role of nicotine in ETS vascular effects. This was confirmed in a second set of experiments (nϭ14), where the sublingual administration of nicotine was associated with an acute impairment in wave reflection as compared with placebo (Pϭ0.001). Both ETS and nontobacco smokes increased plasma asymmetrical dimethyl-arginine levels (PϽ0.001), but only ETS reduced the late rise in skin blood flow in response to heating (Pϭ0.03). In conclusion, passive smoking specifically increases aortic wave reflection through a nicotine-dependent pathway and impairs microvascular function, even after the end of the exposure. However, both tobacco and nontobacco passive smoking inhalation increase plasma asymmetrical dimethyl-arginine levels. Key Words: passive smoking Ⅲ nicotine Ⅲ endothelium Ⅲ wave reflection Ⅲ nitric oxide E xposure to environmental tobacco smoke (ETS) has been recognized recently as a strong contributor to cardiovascular mortality, accounting for Ͼ50 000 deaths annually in the United States. 1 In recent years, extensive research has elucidated many aspects of the long-term ETS-related adverse effects on the cardiovascular system. 1 However, the use of normal air inhalation as a control limits the interpretation of the physiopathological processes underlying the acute cardiovascular toxicity of ETS. [2][3][4] Whether lung irritation and/or the stress provoked by smoke inhalation generate a nonspecific cardiovascular reaction 5 and whether this can explain the effect of ETS 2-4 are not known. We, therefore, decided to test the hypothesis that the vascular effects of ETS cannot simply be ascribed to a nonspecific reaction to smoke. This would provide further clear-cut evidence that ETS exerts specific deleterious cardiovascular effects beyond those of smoke pollution.To further prove the specificity of the toxic effects of ETS, our second new hypothesis was that the deleterious vascular effects of ETS would be related to the rise in plasma nicotine levels. The above-mentioned studies 2-4 did not determine plasma nicotine. The role of nicotine in the changes ...

Abstract-Exposure to diesel exhaust was recently identified as an important cardiovascular risk factor, but whether it impairs nitric oxide (NO)-mediated endothelial function and increases production of reactive oxygen species (ROS) in endothelial cells is not known. We tested these hypotheses in a randomized, controlled, crossover study in healthy male volunteers exposed to ambient and polluted air (n=12). The effects of skin microvascular hyperemic provocative tests, including local heating and iontophoresis of acetylcholine and sodium nitroprusside, were assessed using a laser Doppler imager. Before local heating, skin was pretreated by iontophoresis of either a specific NO-synthase inhibitor (L-N-arginine-methyl-ester) or a saline solution (Control). ROS production was measured by chemiluminescence using the lucigenin technique in human umbilical vein endothelial cells preincubated with serum from 5 of the subjects. Exposure to diesel exhaust reduced acetylcholine-induced vasodilation (P<0.01) but did not affect vasodilation with sodium nitroprusside. Moreover, the acetylcholine/sodium nitroprusside vasodilation ratio decreased from 1.51±0.1 to 1.06±0.07 (P<0.01) and was correlated to inhaled particulate matter 2.5 (r=−0.55; P<0.01). NO-mediated skin thermal vasodilatation decreased from 466±264% to 29±123% (P<0.05). ROS production was increased after polluted air exposure (P<0.01) and was correlated with the total amount of inhaled particulate matter <2.5 μm (PM2.5). In healthy subjects, acute experimental exposure to diesel exhaust impaired NO-mediated endothelial vasomotor function and promoted ROS generation in endothelial cells. Increased PM2.5 inhalation enhances microvascular dysfunction and ROS production.

Granulocyte-colony-stimulating factor administered for autologous hematopoietic stem cell isolation from blood may favor restenosis in patients implanted after acute myocardial infarction (AMI). We therefore tested the isolation of peripheral-blood CD34؉ cells without mobilization in six patients with AMI. After large-volume cytapheresis and positive CD34 ؉ cell selection, 3.6 to 27.6 million CD34؉ cells were obtained. We performed intracoronary implantation of these cells and recorded no restenosis or arrhythmia. We used positron emission tomography (PET) to assess myocardial-labeled CD34 ؉ cell homing, which accounted for 5.5% of injected cells 1 hour after implantation. In conclusion, large amounts of CD34 ؉ cells, in the range reported in previous studies, can be obtained from nonmobilized peripheral blood. PET with [18 F]-fluorodeoxyglucose cell labeling is an efficient imaging method for homing assessment. STEM CELLS 2006;24:333-336

Vitamin D deficiency (VDD) is associated with an increased cardiovascular risk. We investigated the effect of VDD on the cardiovascular system of growing male rats fed with a vitamin D-deficient diet. Using isolated rat aorta, we assessed both superoxide anion and endothelial-dependent relaxations. Microarray technology was used to identify changes induced by VDD in cardiac gene expression. Compared with control, VDD increased systolic blood pressure (P < 0.05) and superoxide anion production in the aortic wall (P < 0.05) and tended to increase serum levels of angiotensin II and atrial natriuretic peptide (P < 0.15). However, VDD slightly improved maximal relaxation to acetylcholine from 75 % ± 3% to 83% ± 2% (P < 0.05). Incubation of aortic rings either with nitro-l-arginine methyl ester (l-NAME) or catalase did not eliminate the enhancement of endothelial-mediated relaxation observed in vitamin D-deficient rats. Only incubation with indometacin or calcium-activated potassium channels blockers suppressed this difference. Compared with control, the expression of 51 genes showed different expression, including several genes involved in the regulation of oxidative stress and myocardial hypertrophy. In conclusion, VDD in early life increases arterial blood pressure, promotes vascular oxidative stress, and induces changes in cardiac gene expression. However, the endothelial-mediated regulation of vasomotor tone is maintained throughout the enhancement of an NO-independent compensatory pathway.