Interestingly, in addition to the increased absorption of salt through NCC in the DCT, the CUL3WT/Δ403–459 mice displayed a thickened aortic wall, altered aortic pulse pressure waveform and in vivo responses to pressor agents that together suggested these mice have an increased contractile state in their vasculature, Thus, the novel vascular phenotype in the CUL3WT/Δ403–459 mice, in addition to the hypertension due to salt retention could possibly explain why FHHt due to CUL3 mutations result in a more severe form of the disease in comparison to FHHt due to mutations in WNK1, WNK4, KLHL3. Here, SLC12A3 is linked to hypertensive disorder.