TY - JOUR
T1 - Renal denervation suppresses coronary hyperconstricting responses after drug-eluting stent implantation in pigs in vivo through the kidney-brain-heart axis
AU - Uzuka, Hironori
AU - Matsumoto, Yasuharu
AU - Nishimiya, Kensuke
AU - Ohyama, Kazuma
AU - Suzuki, Hideaki
AU - Amamizu, Hirokazu
AU - Morosawa, Susumu
AU - Hirano, Michinori
AU - Shindo, Tomohiko
AU - Kikuchi, Yoku
AU - Hao, Kiyotaka
AU - Shiroto, Takashi
AU - Ito, Kenta
AU - Takahashi, Jun
AU - Fukuda, Koji
AU - Miyata, Satoshi
AU - Funaki, Yoshihito
AU - Ishibashi-Ueda, Hatsue
AU - Yasuda, Satoshi
AU - Shimokawa, Hiroaki
N1 - Funding Information:
This work was supported, in part, by the grants-in-aid for the Scientific Research (18890018) and the Global COE Project (F02) and the grants-in-aid (H22-Shinkin-004) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology, Tokyo, Japan, the grant for young investigators of translational research from Tohoku University Hospital, and the grants-in-aid by a Sakakibara Memorial Research Grant from the Japan Research Promotion Society for Cardiovascular Diseases.
Publisher Copyright:
© 2017 American Heart Association, Inc.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Autonomic nervous system
KW - Blood pressure
KW - Coronary vessels
KW - Nerve fibers
KW - Renal artery
KW - Stents
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U2 - 10.1161/ATVBAHA.117.309777
DO - 10.1161/ATVBAHA.117.309777
M3 - Article
C2 - 28818859
AN - SCOPUS:85031016790
SN - 1079-5642
VL - 37
SP - 1869
EP - 1880
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 10
ER -