Renal denervation suppresses coronary hyperconstricting responses after drug-eluting stent implantation in pigs in vivo through the kidney-brain-heart axis

Hironori Uzuka, Yasuharu Matsumoto, Kensuke Nishimiya, Kazuma Ohyama, Hideaki Suzuki, Hirokazu Amamizu, Susumu Morosawa, Michinori Hirano, Tomohiko Shindo, Yoku Kikuchi, Kiyotaka Hao, Takashi Shiroto, Kenta Ito, Jun Takahashi, Koji Fukuda, Satoshi Miyata, Yoshihito Funaki, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Hiroaki Shimokawa

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective - Drug-eluting stent-induced coronary hyperconstricting responses remain an important issue. The adventitia harbors a variety of components that potently modulate vascular tone, including sympathetic nerve fibers (SNF) and vasa vasorum. Catheter-based renal denervation (RDN) inhibits sympathetic nerve activity. We, thus, examined whether RDN suppresses drug-eluting stent-induced coronary hyperconstricting responses, and if so, what mechanisms are involved. Approach and Results - Protocol 1: pigs implanted with everolimus-eluting stents into the left coronary arteries underwent coronary angiography at 1 month after implantation for assessment of coronary vasomotion and adventitial SNF formation. Drug-eluting stent-induced coronary hyperconstricting responses were significantly enhanced associated with enhanced coronary adventitial SNF and vasa vasorum formation. Protocol 2: pigs implanted with everolimus-eluting stents were randomly assigned to the RDN or sham group. The RDN group underwent renal ablation. At 1 month, RDN significantly caused marked damage of the SNF at the renal arteries without any stenosis, thrombus, or dissections. Notably, RDN significantly upregulated the expression of α2-adrenergic receptor-binding sites in the nucleus tractus solitarius, attenuated muscle sympathetic nerve activity, and decreased systolic blood pressure and plasma renin activity. In addition, RDN attenuated coronary hyperconstricting responses to intracoronary serotonin at the proximal and distal stent edges associated with decreases in SNF and vasa vasorum formation, inflammatory cell infiltration, and Rho-kinase expression/activation. Furthermore, there were significant positive correlations between SNF and vasa vasorum and between SNF and coronary vasoconstricting responses. Conclusions - These results provide the first evidence that RDN ameliorates drug-eluting stent-induced coronary hyperconstricting responses in pigs in vivo through the kidney-brain-heart axis.

Original languageEnglish
Pages (from-to)1869-1880
Number of pages12
JournalArteriosclerosis, thrombosis, and vascular biology
Volume37
Issue number10
DOIs
Publication statusPublished - 2017 Jan 1

Keywords

  • Autonomic nervous system
  • Blood pressure
  • Coronary vessels
  • Nerve fibers
  • Renal artery
  • Stents

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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