Role of the nitric oxide on rosuvastatin-induced relaxation of the calf cardiac vein during cooling.

Abstract

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors including rosuvastatin do not only lower plasma cholesterol but also have non-cholesterol lowering effects on the vessel wall, which decrease cardiovascular complications. The aim of the present study was to evaluate the effect of cooling (to 28 °C) on the vasodilatation induced by rosuvastatin (10-9-3x10-4M) on serotonin-pre-contracted calf cardiac vein and the role of nitric oxide in these effects. Ring preparations of veins obtained from calf hearts were suspended in organ baths containing 25 ml of Krebs-Henseleit solution, maintained at 37 °C and continuously gassed with 95% O(2)-5% CO(2). After a resting period, preparations were contracted with serotonin (10-6 M) at 37 °C. Rosuvastatin produced concentration-dependent relaxation of calf cardiac vein precontracted with serotonin (10-6 M). During cooling, the pIC(50) value, but not the maximal response, to rosuvastatin was significantly higher than at 37 °C. Cooling to 28 °C in the presence of NG-nitro-L-arginine methyl ester (L-NAME, 10-4 M) decreased the pIC(50) values to rosuvastatin. The results of the present study suggested that nitric oxide played an essential role in the cooling-induced changes of rosuvastatin in calf cardiac vein (Fig. 1, Ref. 23).