Plasma concentrations of 25(OH)D decrease after an inflammatory insult and therefore are unlikely to be a reliable measure of 25(OH)D status in subjects with evidence of a significant systemic inflammatory response.

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Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase and an important cause of endothelial dysfunction. Its increased plasma concentration is associated with a variety of traditional cardiovascular risk factors, and may mediate their effects on the vascular endothelium. ADMA is also an independent predictor of cardiovascular events and mortality, and predicts outcomes in critically ill patients in the intensive care unit. This work has provided insights into the role of ADMA as an endogenous regulator of nitric oxide synthesis. At present there is no specific therapy to modify ADMA concentration, but increasing interest and work on protein arginine methyltransferases and dimethylarginine dimethylaminohydrolase, which synthesize and metabolize ADMA, respectively, might provide novel therapeutic targets.

BackgroundDiesel exhaust inhalation causes cardiovascular dysfunction including impaired vascular reactivity, increased blood pressure, and arterial stiffness. We investigated the role of nitric oxide (NO) bioavailability in mediating these effects.Methods and ResultsIn 2 randomized double‐blind crossover studies, healthy nonsmokers were exposed to diesel exhaust or filtered air. Study 1: Bilateral forearm blood flow was measured during intrabrachial infusions of acetylcholine (ACh; 5 to 20 μg/min) and sodium nitroprusside (SNP; 2 to 8 μg/min) in the presence of the NO clamp (NO synthase inhibitor NG‐monomethyl‐l‐arginine (l‐NMMA) 8 μg/min coinfused with the NO donor SNP at 90 to 540 ng/min to restore basal blood flow). Study 2: Blood pressure, arterial stiffness, and cardiac output were measured during systemic NO synthase inhibition with intravenous l‐NMMA (3 mg/kg). Following diesel exhaust inhalation, plasma nitrite concentrations were increased (68±48 versus 41±32 nmol/L; P=0.006) despite similar l‐NMMA–induced reductions in basal blood flow (−20.6±14.7% versus −21.1±14.6%; P=0.559) compared to air. In the presence of the NO clamp, ACh and SNP caused dose‐dependent vasodilatation that was not affected by diesel exhaust inhalation (P>0.05 for both). Following exposure to diesel exhaust, l‐NMMA caused a greater increase in blood pressure (P=0.048) and central arterial stiffness (P=0.007), but reductions in cardiac output and increases in systemic vascular resistance (P>0.05 for both) were similar to those seen with filtered air.ConclusionsDiesel exhaust inhalation disturbs normal vascular homeostasis with enhanced NO generation unable to compensate for excess consumption. We suggest the adverse cardiovascular effects of air pollution are, in part, mediated through reduced NO bioavailability.Clinical Trial RegistrationURL: http://www.ClinicalTrials.gov. Unique identifiers: NCT00845767 and NCT01060930.

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