Antifibrotic effect of adrenomedullin on coronary adventitia in angiotensin II-induced hypertensive rats

Abstract

Objective: The extracellular matrix (ECM) determines the structural integrity of the heart and vasculature, participating in cardiovascular remodeling. We previously reported that adrenomedullin (AM) inhibited cellular proliferation and protein synthesis of cardiac fibroblasts; however, the precise mechanisms of AM actions as an antifibrotic factor remain unknown. The purpose of this study was to examine the biological actions of AM against the profibrotic factor angiotensin II (Ang II) in coronary adventitia. Methods and results: Rats with hypertension induced by Ang II infusion were administered 0.06 μg/kg/min recombinant human AM subcutaneously for 14 days. The AM infusion significantly (ppp−7 mol/L AM exerted an inhibitory effect on TGF-β1-induced α-SMA expression (pConclusion: AM decreased Ang II-induced collagen deposition surrounding the coronary arteries, inhibiting myofibroblast differentiation and expressions of ECM-related genes in rats. The present findings further support the biological action of AM as an antifibrotic factor in vascular remodeling.