The effects of chylomicron remnants on the activity of basally produced nitric oxide (NO) from porcine coronary artery rings and porcine aortic endothelial cells were studied by investigating the effects of chylomicron-remnant-like particles (CMR-LPs) containing porcine apolipoprotein E on the vessel tone of porcine coronary arteries and on cGMP release by aortic endothelial cells. CMR-LPs were oxidized by incubation with CuSO4 (10 μM) for 18 h at 37 °C. Nω-nitro-L-arginine (L-NOARG) and oxidized CMR-LPs (oxCMR-LPs), but not native CMR-LPs, increased the vessel tone of static porcine coronary artery rings (increase in tone as a percentage of the tone induced by depolarizing Krebs–;Henseleit solution: L-NOARG, 14.24±2.09; oxCMR-LPs, 4.98±0.88; and native CMR-LPs, 0.47±0.21). L-NOARG, endothelium removal and oxCMR-LPs also all significantly increased the maximum relaxation of the vessels to S-nitroso-N-acetyl-DL-penicillamine. In addition, oxCMR-LPs reduced the amounts of cGMP released by porcine aortic endothelial cells into the culture medium from 116±12.0 to 84.2±11.6 fmol/μg of cellular protein, mimicking the effects of L-NOARG. These results indicate that oxCMR-LPs, but not native CMR-LPs, inhibit the activity, production or release of NO from unstimulated porcine coronary and aortic endothelial cells. oxCMR-LPs mimicked the addition of L-NOARG and endothelium removal in these experimental systems, suggesting that the lipoproteins were interfering with the L-arginine/NO pathway. This study provides further evidence to support a role of chylomicron remnants in the development of atherosclerosis.

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