Smooth muscle specific inactivation of Arhgef1 or G12-G13-LARG, important for rho-kinase signaling, was for instance shown to protect against hypertension development during chronic angiotensin II infusion and DOCA-salt treatment (Wirth et al., 2008; Guilluy et al., 2010) while smooth muscle specific deletion of the NO-activated soluble guanylyl cyclase (Groneberg et al., 2010) or endothelium-specific expression of a dominant negative peroxisome proliferator-activated receptor (PPAR)-γ (Pelham et al., 2013) was found to cause hypertension. The gene discussed is ARHGEF12; the disease is Hypertension.