Journal of Pharmaceutical Research International

Endothelin-1 (ET-1) is predominantly expressed in endothelial cells to modulate physiological actions, such as vasoconstriction and cell proliferation. It acts as an autocrine and paracrine factor, and has been reported to be found in increased levels in the blood of patients with hyperlipidemia and atherosclerosis. The excessive proliferation and migration of vascular smooth muscle cells (VSMCs) characterize the progression of atherosclerosis. Thus, ET-1 is currently believed to be an important factor for atherosclerosis. Endothelin-1 (1-31) is a relatively recently discovered form of ET and is generated from big ET-1 by chymase, which is predominantly expressed in mast cells. Recently, the elevated concentration of circulating ET-1 (1-31) in patients with acute myocardial infarction has been reported. In this study, we investigated whether ET-1 (1-31) could induce VSMC migration and compared its effect with that of ET-1. ET-1 (1-31) significantly stimulated rat aortic vascular smooth muscle cell (RASMC) migration in a concentration dependent manner. ET-1 (1-31) at 100 nM caused a 1.38-fold increase in RASMC migration whereas ET-1 at the same concentration resulted in a 1.60-fold increase. The ET-1 (1-31)-stimulated RASMC migration was significantly inhibited by BQ123, a specific ET_A receptor antagonist, but not by BQ788, a specific ET_B receptor antagonist. These data suggest that ET-1 (1-31) stimulates the VSMC migration through ET_A receptors but not ET_B receptors. The findings presented in this paper bring us one step closer to understanding the mechanisms involved in atherosclerosis.