Spironolactone Improves Hyperthyroxine Induced Atrial Remodeling In Rabbits

Objective:To investigate the effect of spironolactone on hyperthyroxine induced atrial remodeling.Methods:Thirty-three New Zealand rabbits were divided into three groups (n= 11):Control group (C), Hyperthyroxine group (H), Spironolactone group (S). Throxine was given to rabbits in groups H and S by intraperitoneal injection for four weeks, and then spironolactone was given in group S by gavage for two weeks. After the administration, burst stimulation was performed to induce atrial fibrillation (AF). The induction of AF and atrial effective refractory period (AERP) were tested by intracardiac electrophysiology. The real-time PCR, Western blot and immunohistochemistry were performed to detect the protein expression of AF related Ca2+ channel(Cav1.2), K+ channel (Kv1.5, Kv4.3) and gap junction (Cx40, Cx43).Results:Tweenty-four rabbits were survived after the administration,7 in group C,8 in group H and 9 in group S. Spironolactone reduces the induction of AF. No significant differences were found in AERP between group H and group S (AERP200:80.71±4.39ms vs 85.74±7.78ms, P>0.05). Compare to group H, the expression of Cav1.2 protein was significant increase in group S (0.23±0.08 vs 0.49±0.13, P<0.05). The expressions of Kv1.5 mRNA and protein expression in group S were significantly lower than those in H group (mRNA:1.96±0.59 vs 3.76±1.11, P<0.01; WB:2.50 ±0.55 vs 3.46±0.46, P<0.05); and the expression of Kv4.3 protein in group S were significantly decrease, compare to this in group H (5.00±0.88 vs 7.55±1.47, P<0.05). There was significantly decrease in the expression of Cx43 mRNA in group S, compare to this in group H (1.30±0.51 vs 2.27± 0.59, P<0.01); and the expression of Cx40 protein in group H was significantly higher than this in group S (1.44±0.28 vs 0.95±0.26, P <0.05).Conclusion:Spironolactone improves the hyperthyroxine induced atrial remodeling in rabbits, and reduces susceptibility to AF.