Synergistic effects of calcium-channel and angiotensin-receptor blockers on endothelial function and inflammatory responses in a porcine drug-eluting stent model.
BACKGROUND
The rate of stent thrombosis is increased in association with drug-eluting stents (DES) due to delayed endothelialization and prolonged inflammation. Clinical studies have shown that either an angiotensin-receptor blocker (ARB) or a calcium-channel blocker (CCB) can improve endothelial dysfunction and inhibit inflammatory reactions in patients with hypertension. The effects of co-administered CCB and ARB on vascular protection after DES implantation, however, remain unknown.


RESULTS
Pigs (n=24) were implanted with coronary stents and randomly assigned to control, CCB, ARB or CCB + ARB groups. Endothelium-mediated vasodilation at the distal edge was significantly impaired compared to the intact site in the control group (P<0.05), but the difference between two sites in the CCB + ARB group was not significant. The combination produced a synergistic effect at the distal edge compared to the ARB, CCB and control groups (P<0.05). The expression of tumor necrosis factor-alpha and inflammatory cell adhesion were significantly inhibited in the CCB or ARB monotherapy groups compared with the control (P<0.05). The combination of CCB + ARB also improved inflammation.


CONCLUSIONS
Implanted DES exert adverse effects such as endothelial dysfunction and inflammatory reactions. The administration of either a CCB or an ARB reversed this adverse effect. Furthermore, recovery was synergistically enhanced by a CCB combined with an ARB.
Kubota
Naozumi
N
Department of Cardiology, Juntendo University School of Medicine, Tokyo, Japan.
Miyauchi
Katsumi
K
Kasai
Takatoshi
T
Iesaki
Takafumi
T
Kajimoto
Kan
K
Sumiyoshi
Katsuhiko
K
Dohi
Tomotaka
T
Daida
Hiroyuki
H
D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy*; D013552:Swine; D014664:Vasodilation
D057911:Angiotensin Receptor Antagonists; D002121:Calcium Channel Blockers