Biochemical and Biophysical Research Communications, Vol.347, No.2, 394-400, 2006
Atorvastatin inhibits angiotensin II-induced T-type Ca2+ channel expression in endothelial cells
Ca2+ channels are involved in the regulation of vascular functions. Angiotensin 11 is implicated in the development of atherosclerosis and vascular remodeling. In this study, we demonstrated that angiotensin 11 preferentially increased the expression of alpha 1G, a T-type Ca2+ channel subunit, via AT, receptors in endothelial cells. Angiotensin II-induced expression of alpha 1G was inhibited by pretreatment with atorvastatin and the MEK1/2 inhibitor, PD98059. The effect of atorvastatin was reversed by mevalonate and farnesyl pyrophosphate which implicates the activation of the small GTP-binding protein, Ras. Our data indicate that angiotensin 11 induces alpha 1G expression in endothelial cells via AT, receptors, Ras and MEK. Angiotensin II-induced migration of endothelial cells in a wound healing model was inhibited by incubation with mibefradil, a T-type Ca2+ channel blocker. Our data indicate that angiotensin II induces T-type Ca2+ channels in endothelial cells, which may play a role in the development of vascular disorders. (c) 2006 Elsevier Inc. All rights reserved.