nitrogen-dioxide and Hypercholesterolemia

Exposure to single pollutants e.g. particulate matter (PM) is associated with adverse health effects, but it does not represent a real world scenario that usually involves multiple pollutants.. Determine if simultaneous exposure to PM and NO₂ results in synergistic interactions.. Healthy young volunteers were exposed to clean air, nitrogen dioxide (NO₂, 0.5 ppm), concentrated fine particles from Chapel Hill air (PM(2.5)CAPs, 89.5 ± 10.7 µg/m³), or NO₂+PM(2.5)CAPs for 2 h. Each subject performed intermittent exercise during the exposure. Parameters of heart rate variability (HRV), changes in repolarization, peripheral blood endpoints and lung function were measured before and 1 and 18 h after exposure. Bronchoalveolar lavage (BAL) was performed 18 h after exposure.. NO₂ exposure alone increased cholesterol and HDL 18 h after exposure, decreased high frequency component of HRV one and 18 h after exposure, decreased QT variability index 1 h after exposure, and increased LDH in BAL fluid. The only significant change with PM(2.5)CAPs was an increase in HDL 1 h after exposure, likely due to the low concentrations of PM(2.5)CAPs in the exposure chamber. Exposure to both NO₂ and PM(2.5)CAPs increased BAL α1-antitrypsin, mean t wave amplitude, the low frequency components of HRV and the LF/HF ratio. These changes were not observed following exposure to NO₂ or PM(2.5)CAPs alone, suggesting possible interactions between the two pollutants.. NO₂ exposure may produce and enhance acute cardiovascular effects of PM(2.5)CAPs. Assessment of health effects by ambient PM should consider its interactions with gaseous copollutants.

Topics: Adult; Air Pollutants; alpha 1-Antitrypsin; Arrhythmias, Cardiac; Atmosphere Exposure Chambers; Bronchoalveolar Lavage Fluid; Cardiovascular Agents; Cardiovascular System; Cholesterol; Drug Synergism; Female; Heart Rate; Humans; Hypercholesterolemia; Lactate Dehydrogenases; Male; Nitrogen Dioxide; North Carolina; Particulate Matter; Young Adult

Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase inhibitors reduces the incidence of atherosclerosis-related cardiovascular events. Adhesion molecules, regulating interactions between vascular and circulating cells, may play a central role in the pathogenesis of atherosclerosis and related complications. In the present report we examined the impact of the HMG-CoA reductase inhibitor fluvastatin on plasma levels of P-selectin and ICAM-1.. Plasma levels of P-selectin and ICAM-1 were determined using an enzyme immunoassay in 26 patients with type IIa hypercholesterolemia randomized to treatment with either fluvastatin (80 mg/d) or placebo in a double blind fashion for 12 weeks.. Fluvastatin administration reduced either P-selectin (118 +/- 63 vs 81 +/- 36 ng/mL [-31%], P = 0.0015) or ICAM-1 (264 +/- 75 vs 228 +/- 68 ng/mL [-13.7%], P = 0.0033) levels. Fluvastatin also lowered urinary 11-dehydro-TXB2 (1396 +/- 536 vs 1009 +/- 378 pg/mg creatinine [-27%], P = 0.0015) and von Willebrand Factor levels (1456 +/- 716 vs 1203 +/- 527 U/L [-17.4%], P = 0.0275), and a direct correlation was observed between P-selectin and 11-dehydro-TXB2 levels (r = 0.588, P = 0.0033). Patients treated with fluvastatin displayed an increase in nitric oxide (NO) generation, evaluated with measurements of serum NO2-/NO3-, (4.7 +/- 1 vs 8.9 +/- 3.1) mumol/L [98%], P = 0.0046). Moreover, an inverse correlation was observed between NO2-/NO3- and P-selectin (r = -0.420; P = 0.0343), 11-dehydro-TXB2 (r = -0.511; P = 0.0106), or LDL (r = -0.742; P = 0.0002) levels.. These results may provide novel biochemical basis for the beneficial clinical effects of HMG-CoA reductase inhibitors in hypercholesterolemia.

Topics: Adult; Aged; Creatinine; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Indoles; Intercellular Adhesion Molecule-1; Male; Middle Aged; Nitric Oxide; Nitrogen Dioxide; P-Selectin; Thromboxane B2; von Willebrand Factor