Hypertension caused by elevated levels of the blood pressure-regulating hormone aldosterone (Ald) leads to oxidative stress and DNA damage in kidneys of rats. In vitro studies showed a protective role of the transcription factor Nrf2 and adverse effects of NF-κB activation. Here we studied the impact of Nrf2 activation and NF- κB inhibition on Ald-mediated damage. Further, the kidneys were studied for markers of epithelial-mesenchymal transition (EMT). Sprague-Dawley rats were infused with either vehicle or Ald during 28 days. Some rats were additionally treated with sulforaphane (Sulf), an Nrf2-activator or with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Ald-treatment led to increased blood pressure, which was lowered by Sulf and PDTC, respectively. Loss of kidney function induced by Ald was ameliorated by either Sulf or PDTC. Additionally, Ald caused higher levels of double strand breaks, which were reduced by Sulf and also by PDTC. Increased levels of apoptosis in cortex of Ald-treated rats were also reduced by both substances. We could not observe any differences in epithelial or mesenchymal markers after 28 days Ald-treatment. In summary, activation of Nrf2 and as well as inhibition of NF-κB protected from Ald-induced hypertension, kidney damage and DNA lesions.