Author + information
- Su Linbo,
- Kaijun Wang,
- Lijun Wang,
- Fengqiang Dang,
- Yifan Zhang and
- Lianna Xie
The present study was undertaken to investigate the protective effects and mechanisms of atorvastatin on pituitrin-induced coronary artery spasm in rats.
Fifty male SD rats were randomly assigned to five groups (n=10): normal group(no any intervention), control group (saline), atorvastatin group (5mg·kg-1·d-1), nifedipine group (5mg·kg-1·d-1), and combined group (atorvastatin 5mg·kg-1·d-1 and nifedipine 5mg·kg-1·d-1). After 15 days of treatment by intragastric administration(except the normal group), coronary artery spasm was induced by injecting pituitrin(1.5 U·kg-1) through caudal vein. The ultrastrueture of myocardial tissue was observed by electron microscopy. The membrane RhoA protein expression and cytosolic RhoA protein expression of coronary artery tissue was detected by western blot, and RhoA activity was expressed as the ratio of membrane RhoA protein and cytosolic RhoA protein.
1. Pituitrin-induced coronary artery spasm caused the acute myocardial ischemic/anoxic injury, which result in myocardial ultrastructure damage. Prophylactic use atorvastatin had a protective role in coronary artery spasm induced myocardial ultrastructure damage, and combined with nifedipine was more effective. 2. Compared with the normal group, coronary artery RhoA activity in the control group was significantly increased (2.55±0.15 vs 0.81±0.16, P<0.01). Compared with the control group, coronary artery RhoA activity was significantly decreased in the atorvastatin group (0.99±0.34 vs 2.55±0.15, P<0.01), no statistically difference in the nifedipine group (2.21±0.23 vs 2.55±0.15, P=0.08), and significantly decreased in the combined group(1.13±0.42 vs 2.55±0.15, P<0.01).
Atorvastatin could effectively prevent pituitrin-induced coronary artery spasm, and had protective effect on myocardial ultrastructure in rats. The addition of atorvastatin to nifedipine had synergistic effect. Inhibition of RhoA/Rho-kinase pathway involved in the mechanism of atorvastatin preventing coronary artery spasm.