Abstract 10067: Olmesartan Inhibits GTP-Binding Protein Alpha q-Induced Atrial Remodeling in Transgenic Mice.
Introduction: The inhibitory effects of angiotensin II type 1 receptor blockers (ARBs) on the development of atrial fibrillation (AF) are still controversial. We previously demonstrated that a transgenic mouse with transient cardiac expression of activated G protein αq (Gαq-TG; a model of chronic heart failure) develops atrial electrical and structural remodeling, leading to atrial fibrillation (AF). In this study, we examined whether olmesartan, an ARB, can restore atrial electrical and structural remodeling in Gαq-TG mice.
Method and Results: Olmesartan (1 mg/kg/day) or vehicle was orally administered in 20 Gαq-TG mice from 6 weeks to 32 weeks of age. At the age of 32 weeks, systemic blood pressure (SBP) was measured from tail artery using the tail cuff method. Ventricular function was also investigated by two-dimensionally-directed M-mode echocardiography. Surface electrocardiogram (ECG) was measured to examine cardiac electrophysiological remodeling. The degree of fibrosis was also investigated on left atrial sections stained with Masson's trichrome. Mean SBP in olmesartan-treated Gαq-TG mice was similar to that in vehicle-treated Gαq-TG mice. Olmesartan improved ventricular dysfunction, determined by reduction of LV fractional shortening (44.2 ± 2.5 vs. 25.4 ± 1.7 %, p<0.001) in Gαq-TG mice. All of the ECG parameters measured were prolonged in the Gαq-TG mice compared with wild-type (WT) mice. In olmesartan-treated Gαq-TG mice, although the QRS complex were still prolonged, the P interval, PR interval, and collected QT interval did not differ from those in WT mice. In Langendorff-perfused hearts, the incidence of AF induced by rapid atrial pacing was greater in Gαq-TG hearts than in olmesartan-treated Gαq-TG hearts (P < 0.05). Dilatation of the left atrium with thrombus formation was observed in 6 of 10 Gαq-TG hearts but not in any olmesartan-treated Gαq-TG hearts. Moreover, the degree of extensive interstitial fibrosis in the left atrium was greater in Gαq-TG hearts than that in olmesartan-treated Gαq-TG hearts (P < 0.05). These findings demonstrated that olmesartan inhibited atrial electrical and structural remodeling in Gαq-TG mice and suggest that olmesartan would be useful for the treatment of AF induced by Gαq induced-CHF.
- © 2010 by American Heart Association, Inc.