Angiotensin-II Actions and AT1-Receptors During Statin Withdrawal.

Signature Grand, Davie, Florida, USA

Background. Acute discontinuation of statins induces vascular dysfunction and increases cardiovascular events. The mechanisms underlying these events are under investigation. Angiotensin II (AII)-signaling is increased after acute statin withdrawal. Objectives. To investigate whether AII-AT1-receptor expression (AT1-R mRNA) and receptor protein (AT1-R) levels mediate the increase in AII signaling observed after statin withdrawal. Methods and Results. In rat aortic vascular smooth muscle cells (VSMC), simvastatin (0.3-3 μM for 24 hours) inhibited in a concentration-dependent manner AII-stimulated phosphorylation of extracellular-signal regulated kinase 1/2 ERK1/2 (-67+5% with 3 μM; P<0.001), decreased AT1-R mRNA (- 34+ 8 % with 3 μM; P<0.01) and AT1-R protein (- 32+6 % with 3 μM; P<0.01). Removal of simvastatin, led to a rebound increase in mRNA-AT1-R (+39+2 %,