Synergistic effects of calcium-channel and angiotensin-receptor blockers on endothelial function and inflammatory responses in a porcine drug-eluting stent model

Circ J. 2010 Aug;74(8):1704-10. doi: 10.1253/circj.cj-09-0743. Epub 2010 Jun 29.


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.

Methods and 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.

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology*
  • Angiotensin Receptor Antagonists / therapeutic use
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channel Blockers / therapeutic use
  • Drug Synergism
  • Drug-Eluting Stents / adverse effects*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Inflammation / drug therapy*
  • Swine
  • Vasodilation


  • Angiotensin Receptor Antagonists
  • Calcium Channel Blockers