We conclude that the Ang II-induced stimulation of NF-kBtranscriptional pathway is involved in upregulating brain WNK-SPAK-NKCC1 cascade and leadsto worsened ischemic stroke outcomes, indicating WNK-SPAK-NKCC1 complex as therapeutictarget for stroke therapy with comorbid HT. Here, SLC12A2 is linked to ischemic stroke.