Abstract 11317: Long-Term Treatment with Nifedipine Suppresses Coronary Hyperconstricting Responses and Inflammatory Changes Induced by Paclitaxel-Eluting Stent in Pigs in Vivo: Possible Involvement of Rho-Kinase Pathway
Background: Enhanced activity of Rho-kinase, the effectors of the small GTP-binding protein Rho, plays a central role in the pathogenesis of coronary vasospasm. We have previously demonstrated that Rho-kinase pathway is also involved in the coronary hyperconstricting responses and vascular lesion formation following drug-eluting stent (DES) implantation in pigs in vivo. In this study, we examined whether long-term treatment with calcium channel blocker suppresses the DES-induced abnormalities.
Method and Results: Paclitaxel-eluting stent (PES) and a bare-metal stent (BMS) were randomly implanted in the left coronary arteries in male domestic pigs, which were treated with and without long-acting nifedipine (NIF, 4 mg/kg/day) for 4 weeks (n=7, each). At least 24 hours after withdrawal of NIF, coronary vasomotion was evaluated in vivo. In the control group, coronary vasoconstricting responses to serotonin (5-HT, 10 and 100 μg/kg, IC) were significantly enhanced at the PES site compared with the BMS site, and were abolished by hydroxyfasudil (HF, 90 and 300 μg/kg, IC), a selective Rho-kinase inhibitor (Figure-A). This enhanced vasoconstricting responses at the PES site were abolished in the NIF group (Figure-B). Histological examination showed inflammatory cell accumulation and enhanced Rho-kinase activity (as evaluated by immunostaining for the extent of phosphorylation of the downstream target, myosin binding subunit) at the PES site in the control group, both of which were suppressed in the NIF group.
Conclusions: These results indicate that long-term treatment with NIF suppresses DES-induced coronary abnormalities partly by inhibiting Rho-kinase pathway in vivo.
- © 2010 by American Heart Association, Inc.