u-0126 and lacidipine

Dihydropyridine calcium channel blockers (CCBs) are more effective in reducing carotid intima-media thickness (IMT) than other classes of antihypertensive drugs due to their vascular effects. However, the mechanism remains to be elucidated.. Ox-LDL induced HUVSMCs proliferation in a time- and dose-dependent manner. When pretreated with three CCBs before 50 μg/ml ox-LDL stimulation, 30 μM lacidipine and 3 μM amlodipine exhibited 27% and 18% decrease of pro-proliferative effect induced by ox-LDL, whereas (S-)-amlodipine did not have any anti-proliferative effect. 30 μM lacidipine inhibited about two-thirds of the ox-LDL induced ROS production in HUVSMCs, whereas amlodipine and (S-)-amlodipine did not have influence on ROS production. The MAPKs pathway inhibitors inhibited the ox-LDL induced proliferation of HUVSMCs.. Our study has demonstrated that lipophilic CCBs, such as lacidipine may inhibit ox-LDL induced proliferation and oxidative stress of VSMCs, and that the ROS-MAPKs pathway might be involved in the mechanism.

Topics: Amlodipine; Anthracenes; Butadienes; Calcium Channel Blockers; Cell Proliferation; Cells, Cultured; Dihydropyridines; Dose-Response Relationship, Drug; Humans; Imidazoles; JNK Mitogen-Activated Protein Kinases; Lipoproteins, LDL; MAP Kinase Signaling System; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nitriles; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Pyridines; Reactive Oxygen Species; Time Factors