Abstract
We reported that oxidative stress associated with aging contributes to diminished natriuretic response to dopamine in old (24‐month) Fischer 344 rats. Here, we explored whether 3‐month exercise in old rats reduces oxidative stress and restores natriuretic response to D1 receptor activation. In old rats, 3‐month treadmill exercise decreased oxidative stress marker malondialdehyde in renal proximal tubules (RPTs) compared to sedentary controls. In the exercised animals, western blotting analyses showed an increase in the expression of antioxidant enzymes, hemeoxygenase 1 and superoxide dismutase. Moreover, nuclear expression of transcription factors, NFkB and Nrf2, was higher in exercised compared to sedentary rats. Electrophoretic mobility shift assay (EMSA) showed an increased nuclear NFkB‐DNA binding in exercised rats. Also, exercise improved D1 receptor expression as evidenced by increased receptor protein content and receptor numbers and restored D1 receptor agonist (SKF 38393) induced natriuresis and diuresis compared to controls. These results suggest that long‐term exercise increases antioxidant defenses involving NFkB and Nrf2 in RPTs, which contributes to decrease in oxidative stress and restores D1 receptor function in old rats. We conclude that exercise as an intervention may be beneficial in attenuating age‐related decline in renal function. [NIH/NIA, AG25056 funded the study].
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