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

Ryuji Tsuburaya, Satoshi Yasuda, Takashi Shiroto, Yoshitaka Ito, Jun Yi Gao, Kentaro Aizawa, Yoku Kikuchi, Kenta Ito, Jun Takahashi, Hatsue Ishibashi-Ueda, Hiroaki Shimokawa

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Aims Accumulating evidence indicates that coronary vasoconstricting responses are enhanced at the edges of coronary segment implanted with a drug-eluting stent (DES) compared with a bare-metal stent (BMS) in humans. We have recently demonstrated that Rho-kinase pathway plays an important role in DES-induced coronary hyperconstricting responses associated with inflammatory changes in pigs in vivo. This study examined whether long-term treatment with calcium channel blocker suppresses DES-induced coronary hyperconstricting responses in pigs in vivo.Methods and resultsPaclitaxel-eluting stent (PES) and a BMS were randomly implanted in the left coronary arteries in male domestic pigs with and without long-acting nifedipine (NIF, 4 mg/kg/day) for 4 weeks (n 7 each). Coronary vasomotion was evaluated by quantitative coronary angiography at least 24 h after withdrawal of NIF to avoid its direct effects on coronary vasomotion. In the control group (without NIF), coronary vasoconstricting responses to serotonin (10 and 100 g/kg, i.c.) were significantly enhanced at the PES site compared with the BMS site (P < 0.009), which were abolished by hydroxyfasudil (90 and 300 g/kg, i.c.), a selective Rho-kinase inhibitor. The PES-induced vasoconstricting responses were significantly inhibited in the NIF group (P = 0.019). Histological examination showed that inflammatory cell accumulation and microthrombus formation were enhanced at the PES site compared with the BMS site (P < 0.05), both of which were significantly suppressed by NIF associated with reduced Rho-kinase expression and activity (P < 0.05). Conclusion These results indicate that long-term treatment with NIF suppresses PES-induced coronary abnormalities partly through Rho-kinase pathway inhibition in vivo.

Original languageEnglish
Pages (from-to)791-799
Number of pages9
JournalEuropean Heart Journal
Volume33
Issue number6
DOIs
Publication statusPublished - 2012 Mar 1

Keywords

  • Calcium channel blockers
  • Coronary vasospasm
  • Drug-eluting stents

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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