Simvastatin improves cardiovascular sympathetic modulation and endothelial function of resistance arteries from hypercholesterolemic mice

Abstract

Can simvastatin treatment (S) alter sympathetic cardiovascular control and mesenteric resistance arteries (MRA) relaxation of LDL receptor knock out (L) mice? Male L mice were treated with S (2 mg/kg, i.p., 7 days) or vehicle. C67Bl/6 mice were used as control (C). Total cholesterol (TC), blood pressure (BP) and autonomic modulation were analyzed. MRA rings were studied in an isometric myograph. Concentration-response curves to Ach (0.01nM-30μM) were obtained in rings incubated for 30 min with L-NAME (100 μM), a NOS inhibitor, tetraethylammonium (TEA; 5mM), a K+ channel blocker, or with vehicle. TC was 3x higher and BP was increased (systolic:30%, diastolic:7%) in L vs. C whereas S had no effect. Cardiac autonomic balance, which was 3x higher, and sympathetic modulation to the vessels, 5x higher in L vs. C, were significantly reduced in L+S (17 and 57%, respectively). MRA % of relaxation to Ach was impaired in L (37±2%) vs. C (92±5%) while S restored it to 70±6%. In C MRA, L-NAME and TEA inhibited Ach-induced relaxation in 46±8% and 74±5%, respectively (p<0.05 L-NAME vs. TEA). This inhibition was ~90±2% in L for both drugs (p<0.05 vs. C); while S shifted it to 70±7% of relaxation inhibition (p<0.05 vs. C and L). S partially restored MRA endothelial function in L mainly by modulating NO concomitantly with an improved autonomic cardiovascular control even without changes in systemic BP and lipid levels.