Effect of angiotensin II receptor antagonist on left ventricular remodeling

Abstract

Masunori Matsuzaki (Yamaguchi University) (Background) The recently developed concept of a local renin-angiotensin system has raised the possibility of a pathophysiological role of angiotensin II in the development and progression of cardiac hypertrophy, cardiac fibroblast hyperplasia, and collagen synthesis via its growth-promoting effect on cardiac myocyte. Here, we assessed the effects of angiotensin II receptor antagonist (TCV-116, FK-739) on left ventricular (LV) remodeling in the two different types of pressure-overloaded heart models. (Methods and Results) 1) TCV-116 (3mg/kg/day) was administered to abdominal aortic banded rats over 4 weeks, then hemodynamics and morphology were evaluated. TCV-116 induced a significant decrease in LV wall thickness, LV weight and myocyte width. In addition, myocyte length was also decreased in association with a reduction in LV midwall radius. 2) FK-739 (30mg/kg/day) or enalapril (10mg/kg/day) were administered to spontaneously hypertensive rats (SHRs) over 6 weeks. Both drugs decreased LV weight and wall thickness to a similar extent. Furthermore, FK-739 caused a greater decrease in LV collagen content than enalapril. (Conclusion) Angiotensin II receptor antagonist might modulate myoeyte remodeling and also collagen metabolism upon prevention or regression of pressure-overload cardiac hypertrophy.