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  • Title: Enalapril, irbesartan, and angiotensin-(1-7) prevent atrial tachycardia-induced ionic remodeling.
    Author: Liu E, Xu Z, Li J, Yang S, Yang W, Li G.
    Journal: Int J Cardiol; 2011 Feb 03; 146(3):364-70. PubMed ID: 19732978.
    Abstract:
    BACKGROUND: Atrial fibrillation (AF) is associated with activation of the renin-angiotensin system (RAS) in the atria. Angiotensin-(1-7) [Ang-(1-7)] is a biologically active component of the RAS, it not only counterbalances the actions of angiotensin II (Ang II) but also is a potential inhibitor of angiotensin-converting enzyme (ACE). The purpose of this study was to investigate the effects of the ACE inhibitor enalapril, the angiotensin-receptor blocker (ARB) irbesartan, and Ang-(1-7) on the chronic atrial ionic remodeling. METHODS: Thirty dogs were assigned to sham, paced, paced + enalapril, paced + irbesartan or paced + Ang-(1-7) group, 6 dogs in each group. Rapid atrial pacing at 500 beats per minute was maintained for 14 days, but dogs in sham group were instrumented without pacing. During the pacing, enalapril (2 mg · Kg(-1) · d(-1)) and irbesartan (60 mg · Kg(-1) · d(-1)) were given orally and Ang-(1-7) (6 μg · Kg(-1) · h(-1)) was given intravenously. Whole-cell patch-clamp technique was used to record atrial ionic currents and action potential duration (APD). And RT-PCR was applied to assess atrial mRNA expression of I(TO) Kv4.3 and I(CaL)α1C subunits. RESULTS: Compared with sham, rapid pacing shortened APD90 (P < 0.05) of atrial myocytes, and decreased APD90 rate adaptation (P<0.05). APD90 changes were prevented by irbesartan and Ang-(1-7), but not enalapril. In atria from paced group, the densities and gene expression of I(TO) and I(CaL) were reduced (P < 0.01 vs. sham). Enalapril increased the density and gene expression of I(TO) compared with sham (P < 0.01), Ang-(1-7) prevented the decrease of I(TO) and I(CaL) (P < 0.05 vs. control) and Kv4.3 mRNA expression (P < 0.01 vs. control). Irbesartan had no effect on I(TO) and I(CaL) densities or mRNA expression. CONCLUSIONS: These results suggest that enalapril, irbesartan, and Ang-(1-7) have differing influences on atrial tachycardia-induced atrial ionic remodeling.
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