Modulation of oxidative stress and antioxidants by losartan in heart failure

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Khaper, Neelam
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In patients surviving a myocardial infarction M), the heart undergoes a remodefing process characterized by hypertrophy which can also lead to heart failure. Although hypertrophy is an early response that may temporarily preserve cardiac function, numerous studies have suggested that this long term process of remodefing is also associated with an increase in oxidative stress and cardiac decompensation. The objectives of the present research on rat hearts subsequent to MI therefore, were to: (i) characterize changes in the oxidative stress and enzymatic antioxidants, (superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase) in relation to their rnRNA abundance and protein content; (ii) study changes in nonenzymatic antioxidants at different stages of heart failure in relation to cardiac function in order to have a more comprehensive information about the antioxidant reserve, and (iii) study the effects of RAS inhibition at the AT1 receptor site by losartan on the myocardial enzymatic and non-enzymatic antioxidants (SOD, GSHPx, catalase, vitamins A and E) and oxidative stress (Lipid hydroperoxides, reduced and oxidized glutathione and the redox ratio) in relation to the changes in hemodynamic function during the sequelae of congestive heart failure. It is concluded that inhibition of the RAS at the AT1 receptor site with losartan, in addition to reducing cardiac remodeling and improving hemodynamic function, reduces oxidative stress and improves myocardial endogenous antioxidants subsequent to myocardial infarction. The study suggests a newer role for losartan in the treatment of heart failure. Although changes in the SOD and catalase activities during heart failure correlated with changes in mRNA for these enzymes, the precise mechanism/s for decrease in oxidative, stress and improvement in antioxidant reserve after losartan treatment is/are unclear at this time. (Abstract shortened by UMI.)