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

2008
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Metric Options:   Counts1 Year3 Year

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Poster Description

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 %,

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