Fluvastatin Enhances the Inhibitory Effects of a Selective Angiotensin II Type 1 Receptor Blocker, Valsartan, on Vascular Neointimal Formation

Abstract

Background— The present studies were undertaken to investigate the potential effect of a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) to enhance the inhibitory effect of an angiotensin (Ang) II type 1 (AT1) receptor blocker (ARB) on vascular neointimal formation and to explore the cellular mechanism of cross-talk of the AT1 receptor and statin in vascular smooth muscle cells (VSMCs). Methods and Results— Neointimal formation and the proliferation of VSMCs induced by cuff placement around the femoral artery were significantly inhibited by treatment with an ARB, valsartan, at a dose of 0.1 mg · kg−1 · d−1 and with fluvastatin at a dose of 1 mg · kg−1 · d−1, which did not influence mean arterial blood pressure or plasma cholesterol level, whereas valsartan or fluvastatin alone at these doses did not affect neointimal formation or the proliferation of VSMCs. Pretreatment with fluvastatin (≈5 μmol/L) for 24 hours significantly inhibited Ang II (1 μmol/L)–mediated DNA synthesis and c-fos promot...