ABSTRACT
Simvastatin is one of the 3-Hydroxy-3-methylglutaryl coenzyme A reductase [HMG-Co-A] inhibitors known for their hypocholesterolemic effect. Apart from cholesterol lowering, simvastatin exerts other beneficial effects such as reduction of plasma fibrinogen and platelet aggregation, anti-inflammatory, anti-proliferative effects, and decreasing risk of coronary heart disease [CHD] and myocardial infarction. This work aimed at investigating the possible modifying effect of simvastatin on systemic vascular reactivity. Vascular responses to various vasoactive agents were tested on isolated rabbit aortic ring preparations obtained at the end of 16 week duration from control normocholesterolemic [group 1], hypercholesterolemic [group 2] as well as simivastatin-treated normocholesterolemic [group 3] and simvastatin-treated hypercholesterolemic [group 4] animal groups. Hypercholesterolemia was induced in groups 2 and 4 by a high cholesterol diet for the 16 weeks. Treated groups [3 and 4] received simvastatin in a daily dose of 10 mg/kg for 8 weeks starting by the beginning of the 9[th] week. In addition to vascular reactivity studies, plasma cholesterol levels were measured for all animals at the ends of 4[th], 8[th], 12[th] and 16[th] weeks. Simvastatin pretreatment significantly reduced plasma cholesterol levels in group 4 animals in comparison to group 2, decreased contractile responses to nor epinephrine [NE] and augmented relaxation induced by acehylcholine [ACh] in nomocholesterolemic [group 3] and treated hypercholesterolemic [group 4] animals compared with control or hypercholesterolemic groups, respectively. In addition, it augmented sodium nitroprusside [SNP] induced relaxant responses in tissues obtained from group 4 compared with group 2. The vasoprotective effects observed with simivastatin therapy may be mainly attributed to improvement of vascular endothelial function not only under hypercholesterolemic- but also normocholesterolemic conditions. Thus simvastatin therapy may be applied not only to reduce the risk of CHD but also the systemic vascular complications associated with hypercholesterolemia. In addition simvastatin might serve as a prophylactic agent against disturbed vascular reactivity that may develop under certain pathological conditions devoid of hypercholesterolemia