Endothelin Receptor Blockade and In-Stent Restenosis

The aim of the present study was to test whether oral dosing of an endothelin (ET) receptor antagonist was able to reduce restenosis in the model of stent-induced restenosis. After pigs underwent coronary artery catheterization they were randomly allocated either to controls or to treatment with the ET receptor antagonist BSF 208075. Thirty-seven pigs underwent percutaneous transluminal coronary angioplasty plus stent implantation; seven animals died of ventricular fibrillation due to procedure-related myocardial ischaemia. From the 30 surviving animals coronary arteries were sampled after 6 weeks of oral treatment with 10 mg/kg/day BSF 208075 or vehicle and histologically evaluated. Stent implantation had no effect on total coronary artery diameter, and media thickness was virtually identical in the two groups. However, neointimal thickness in the group treated with the ET receptor antagonist was significantly reduced, resulting in a significantly larger total coronary artery lumen in the treated group. As in the setting of stent implantation neither 'recoil' nor scar-related vascular remodelling can occur, this result allows the conclusion of a significant antiproliferative effect of ET receptor antagonism in pig coronary arteries.