Abstract 268: Angiotensin II Up-regulates Serum and Glucocorticoid Inducible Kinase 1 in Remodeled Blood Vessels
Angiotensin II (Ang II) is a potent vasoconstrictor that activates vascular smooth muscle and in excess amounts is an important contributing factor in the development of hypertension. However, the downstream signaling pathways mediating the effects of Ang II in the vasculature is not fully known. The present study examines the regulation of serum- and glucocorticoid inducible kinase (SGK1) a serine/threonine kinase that has been implicated in hyperglycemia- and salt-induced hypertension. We hypothesized that SGK1 is up-regulated in pathologically remodeled blood vessels in the context of Ang II-induced hypertension and by Ang II in vascular smooth muscle cells in vitro. Therefore, we examined SGK1 protein expression in human aortic smooth muscle cells (HASM) stimulated with increasing doses of Ang II (0-100nM) in vitro. Our results demonstrated a dose-dependent increase in SGK1 protein expression. SGK1 expression was increased approximately 10-fold following 60 minutes of stimulation with 100nM Ang II. Next, we examined SGK1 expression in the vasculature in vivo in a mouse model of Ang II-induced hypertension. Based on immunohistochemistry, our data indicated that SGK1 was up-regulated in the medial layer of the aorta in mice infused with 0.7mg/kg/day Ang II, a dose that significantly increases blood pressure. Overall, these results indicate that Ang II up-regulates SGK1 in both smooth muscle cells and blood vessels. Our results also suggest that SGK1 may be responsible for the increase in blood pressure and remodeling of the blood vessels.
- © 2012 by American Heart Association, Inc.