Lovastatin maintains nitric oxide -: but not EDHF-mediated endothelium-dependent relaxation in the hypercholesterolemic rabbit carotid artery

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 mu M) 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 (10 mu M). Lovastatin selectively maintains nitric oxide-mediated endothelium-dependent relaxation in hypercholesterolemic rabbit carotid arteries. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.