Lovastatin maintains nitric oxide—but not EDHF-mediated endothelium-dependent relaxation in the hypercholesterolemic rabbit carotid artery Original Research Article

The endothelium contributes to the regulation of vascular tone by producing nitric oxide (NO) and the endothelium-derived hyperpolarising factor (EDHF). In hypercholesterolemia, endothelium-dependent relaxation is impaired but can be restored by treatment with lovastatin (LOVAS). We investigated the effects of LOVAS on NO and EDHF-mediated relaxation. Rabbits were fed 1% cholesterol diet for 4 weeks and 0.5% cholesterol for the following 12 weeks (CHOL-group). The LOVAS group additionally received 10 mg of lovastatin over the last 12-week period. Experiments were performed in carotid artery rings. Relaxant responses to acetylcholine (ACh) were recorded in the presence of indomethacin. Nitro-l-arginine (NOARG, 100 μM) and potassium chloride (KCl, 35 mM) were used to differentiate between NO- and EDHF-mediated relaxations. Cholesterol impaired ACh-induced relaxations and this effect was prevented by LOVAS (control 100±1%, CHOL 81±6%, LOVAS 98±1%). In the presence of NOARG, relaxations to ACh were not different between the LOVAS and CHOL groups (control 78±4%, CHOL 64±6%, LOVAS 64±5%). When KCl was used, ACh-induced relaxations were similar in the LOVAS and control group (control 75±5%, CHOL 49±6%, LOVAS 76±2%). In arteries treated with NOARG and KCl together, no relaxations were observed. Relaxations of arteries from the control group were not affected by 18 h preincubation with lovastatin (10μM). Lovastatin selectively maintains nitric oxide-mediated endothelium-dependent relaxation in hypercholesterolemic rabbit carotid arteries.