Mineralocorticoid receptors are implicated in the initial steps of the cardiorenal damage induced by ethanol.

BACKGROUND

Oxidative stress is an early mediator of ethanol-induced cardiorenal injury and dysfunction. The enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a key role in the generation of reactive oxygen species (ROS) triggered by ethanol. In certain tissues, the pro-oxidative and pro-inflammatory effects of ethanol occur via activation of mineralocorticoid receptors (MR). We hypothesized that MR blockade would prevent the redox imbalance induced by ethanol during the early stages of cardiac and renal changes.

METHODS

Male Wistar Hannover rats were treated with ethanol for five weeks. The contribution of the MR pathway to the cardiorenal effects of ethanol were evaluated with potassium canrenoate, an antagonist of the MR (MRA).

RESULTS

Blockade of MR prevented the increase in lipoperoxidation and superoxide (O2•-) levels in the left ventricle and renal cortex of ethanol-treated rats. Increased concentrations of hydrogen peroxide (H2O2) were detected in the renal cortex, but not in the left ventricle of ethanol-treated rats, and treatment with the MRA prevented this response. Ethanol augmented cardiac levels of thromboxane (TX)B2, a stable metabolite of TXA2 and the renal concentration of prostaglandin (PG)E2. These responses were abrogated by MR blockade.

CONCLUSION

The MR pathway mediates pro-oxidative effects in the early stages of ethanol-induced cardiorenal dysfunction.