I009 Angiotensinii induced atrial remodelling is worsened in mice overexpressing aldosterone synthase in cardiomyocyte

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The aim of this work was to check the hypothesis that increased cardiac aldosterone level combined with arterial hypertension may be deleterious for the heart. Transgenic mice overexpressing Aldo Synthase (AS) in cardiomyocytes and wild type (WT) littermates were submitted to AngII treatment by osmotic pump (1 mg/kg/day) during 3 and 8 weeks. 1) Same levels of hypertension were observed in all treated groups whatever the genotype. Ventricular remodelling was equivalent in terms of LVH at 3wks and 8 wks in AngII-treated groups (ratio HW/BW +10 % for AS and WT after AngII, p<0.05) and fibrosis (×3 for AngII groups, p<0.05). Eplerenone treatment (50 mg/kg/day) prevented these changes. In contrast, after 3 wks of AngII treatment atrial remodelling was worsened with increased dilatation (0.220±0.003 cm vs 0.200±0.003 cm for WT, p<0.05) and fibrosis (3.13±0.26 % vs 2.64±0.16 % for WT, p<0.05) in AS mice. This phenotype was aggravated in 8 weeks treated mice with an atrial diameter of 0.240±0.004 cm in AS vs 0.220±0.004 cm (p<0.05) in WT mice. Atrial fibrosis was 4.2±0.6 % in AS vs 3.6±0.2 % in WT (p<0.55). We also observed a longer P wave duration in AS mice after AngII than in WT (for 3 wks treatment, 18.78±0.45 ms vs 17.15±0.38 ms for WT, p<0.01 and at 8 wks 22.00±0.42 ms vs 20.98±0.83 ms for WT, p<0.05). 2) This electrical change led us to study the expression of atrial connexin (Cx) 40 and 43. AS mice showed a decrease of about 50 % of C×43 at basal state compared to WT but C×40 levels remained unchanged. AngII treatment decreased about 50 % C×43 and C×40 expression in WT mice. For AS mice, AngII induced an increase of about 50 % of C×40 expression but C×43 expression was not affected. In conclusion, these results suggest that cardiac aldosterone combined with AngII hypertension have deleterious effects on left atria: it increases dilatation and fibrosis and it increases conduction time by regulating expression of C×40 and 43.