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

Abstract

Background: The rate of stent thrombosis is increased in association with drug-eluting stents (DES) due to delayed endothelialization and prolonged infammation. Clinical studies have shown that either an angiotensin-receptor blocker (ARB) or a calcium-channel blocker (CCB) can improve endothelial dysfunction and inhibit infammatory 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 signifcantly 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 signifcant. 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-o- and infammatory cell adhesion were signifcantly inhibited in the CCB or ARB monotherapy groups compared with the control (P<0.05). The combination of CCB+ARB also improved infammation.&Conclusions: Implanted DES exert adverse effects such as endothelial dysfunction and infammatory reactions. The administration of either a CCB or an ARB reversed this adverse effect. Furthermore, recovery was synergisti-cally enhanced by a CCB combined with an ARB.