Adrenomedullin is a potent inhibitor of angiotensin II-induced migration of human coronary artery smooth muscle cells

Hypertension
M KohnoJ Yoshikawa

Abstract

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(6) and 10(8) 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 recep...Continue Reading

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Citations

Mar 29, 2002·Microscopy Research and Technique·Mercedes GarayoaLuis M Montuenga
Mar 29, 2002·Microscopy Research and Technique·Ted H Elsasser, Stas Kahl
Feb 20, 2004·Current Hypertension Reports·Katsuyuki AndoToshiro Fujita
Mar 14, 2000·Life Sciences·M Jougasaki, J C Burnett
May 22, 1998·Journal of Cardiovascular Pharmacology·M KohnoJ Yoshikawa
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Jun 6, 2002·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Masakazu KohnoKoji Ohmori
Mar 13, 2003·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Kazutoshi MiyashitaKazuwa Nakao
Oct 26, 2001·Biochemical and Biophysical Research Communications·I MakinoT Kawarabayashi
Sep 14, 2004·Journal of Hypertension·Naohisa HosomiJames A Koziol
Apr 18, 2001·Current Cardiology Reports·J G Lainchbury
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Mar 11, 2005·Endocrine Journal·Tatsuo Shimosawa, Toshiro Fujita
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Dec 10, 1999·Journal of the American Society of Nephrology : JASN·M KohnoJ Yoshikawa
Sep 29, 1998·Metabolism: Clinical and Experimental·M KohnoJ Yoshikawa

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