Orally Administered Rapamycin Does Not Modify Rat Aortic Vascular Tone

Abstract

Rapamycin (RP; rapamune, sirolimus) is a potent inhibitor of vascular smooth muscle cell proliferation and migration. RP was demonstrated to reduce vascular neointimal formation in different animal models of vascular smooth muscle cell proliferation, and clinical use of RP-eluting stents promotes significant reductions in in-stent restenosis rates. However, high costs still preclude the widespread use of these devices. Oral administration of RP associated to bare metal stent delivery has been advocated as an effective and considerably less expensive alternative for restenosis prevention. It is noteworthy that the presence of RP-eluting stents has been associated with reduced endothelial-dependent vasodilation and coronary spasm. In addition, RP has been demonstrated to prevent vasculogenesis. This study evaluated the effects of RP on endothelium-dependent vascular tone and demonstrated that in vitro incubation with high concentrations of RP did not modify either contraction or relaxation of aortic rings. Similar results were obtained after in vivo administration of the drug. These findings suggest that function of adult, non-proliferative rat endothelial cells involved in vascular tone control is not affected by orally administered RP.