Adrenomedullin Is a Potent Inhibitor of Angiotensin II-Induced Migration of Human Coronary Artery Smooth Muscle Cells

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 29; no. 6; pp. 1309 - 1313
• Main Authors: Kohno, Masakazu, Yokokawa, Koji, Kano, Hiroaki, Yasunari, Kenichi, Minami, Mieko, Hanehira, Takao, Yoshikawa, Junichi
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.06.1997; Hagerstown, MD Lippincott
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Adrenomedullin; Angiotensin II - antagonists & inhibitors; Angiotensin II - pharmacology; Antihypertensive Agents - pharmacology; Biological and medical sciences; Biphenyl Compounds - pharmacology; Cardiology. Vascular system; Cell Movement - drug effects; Cells, Cultured; Coronary heart disease; Coronary Vessels - drug effects; Dose-Response Relationship, Drug; Heart; Humans; Imidazoles - pharmacology; Losartan; Medical sciences; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Peptides - pharmacology; Tetrazoles - pharmacology; Vasodilator Agents - pharmacology; Human; Cell culture; Peptides; Pathogenesis; Migration; Coronary artery; Adrenomedullin; Cardiovascular disease; Smooth muscle; Coronary heart disease; Myocyte; Vascular disease; Atherosclerosis; Angiotensin antagonist; Angiotensin II
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.29.6.1309

The migration of coronary artery medial smooth muscle cells (SMCs) into the intima is proposed to be an important process of intimal thickening in coronary atherosclerotic lesions. In the current study, we examined the possible interaction of adrenomedullin, a novel vasorelaxant peptide, and angiotensin II (Ang II) on human coronary artery SMC migration using Boyden's chamber method. Ang II stimulated SMC migration in a concentration-dependent manner between 10 and 10 mol/L. This stimulation was clearly blocked by the Ang II type 1 receptor antagonist losartan but not by the type 2 receptor antagonist PD 123319. The migration stimulatory effect of Ang II was chemotactic in nature for cultured human coronary artery SMCs but was not chemokinetic. Human adrenomedullin clearly inhibited Ang II-induced migration in a concentration-dependent manner. Human adrenomedullin stimulated cAMP formation in these cells. Inhibition by adrenomedullin of Ang II-induced SMC migration was paralleled by an increase in the cellular level of cAMP. 8-Bromo-cAMP, a cAMP analogue, and forskolin, an activator of adenylate cyclase, inhibited the Ang II-induced SMC migration. These results suggest that Ang II stimulates SMC migration via type 1 receptors in human coronary artery and adrenomedullin inhibits Ang II-induced migration at least partly through a cAMP-dependent mechanism. Taken together with the finding that adrenomedullin is synthesized in and secreted from vascular endothelial cells, this peptide may play a role as a local antimigration factor in certain pathological conditions. (Hypertension. 1997;29:1309-1313.)