P487 Isoprenaline induced heart remodelling differentially influences dystrophin and MnSOD expression in Wistar and SHR rats

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Purpose: Progression of heart remodelling and failure may be associated with disturbances of sarcoplasm membrane stability, and changes of redox balance. The lack of dystrophin protein has been revealed during heart failure development but the changes in expression of dystrophin during remodeling progress are not enough investigated, as well as expression of inducible anti-oxidant enzyme MnSOD. The aim of the study was to determine the expression of dystrophin and MnSOD in the dynamic of hypertrophy of the left ventricle.

Methods: In male Wistar and SHR rats 6 months in age, hypertrophy was induced by low doses of isoprenaline (ISO) injections for 7 days. For control we injected 0,9 % NaCl solution at the same period. The samples of left (LV) and right (RV) ventricle tissue were collected in the dynamics of experiment, and morphometric analyze was performed. The expression of dystrophin was determined by Western blotting. The parameters of heart function were investigated using the ultra-small catheter 2F ("Millar Instruments", USA).

Results: In both lines of animals, the progressive hypertrophy of LV was revealed, and following regression of hypertrophy was shown (only partially in SHR). We found that the parameters of heart function in both lines of animals were typical for heart remodeling and these changes were strongly pronounced in SHR. The expression of dystrophin was higher in RV of Wistar rats. The maximal increase in 5th day with following reduction was observed. In SHR, dystrophin expression was significantly lesser, the maximal reduction was found on 30th day. In both lines of rats, MnSOD expression was higher in LV. In the LV of Wistar, the rise and regression of hypertrophy was accompanied with increase and reduction of MnSOD expression. In the RV of Wistar, moderate elevation of MnSOD was kept during 5-14 days, and maximal values were in 30th day. In opposite, in the LV of SHR, MnSOD expression was dramatically reduced in 5-7 days during maximum of hypertrophic response that may reflect significant disturbances of anti-oxidant defence.

Conclusions: The data demonstrate that hypertrophy of LV induced by adrenergic stimulation in rats is accompanied by transient compensatory increase of dystrophin expression, which is less pronounced in SHR. However, the followed prolonged depletion of dystrophin in myocardium, especially in SHR, may be unfavorable for remodelling progression. Anti-oxidant effect of MnSOD protects the heart during one month, but in SHR this mechanism appears to be insufficient at considerable hypertrophy.

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