Activation of Rho kinase by angiotensin II (Ang II) is involved in the pathophysiology of hypertension and remodeling. Rho kinase activation also controls plasminogen activator inhibitor-1 (PAI-1) production which promotes vessel wall fibrosis and contributes to atherogenesis. In Bartter's and Gitelman's syndromes (BS/GS) short term signaling pathway of Ang II which mediated most hemodinamic and endocrine effects of Ang II, is blunted (reduced Gαq gene expression, intracellular IP3 and Ca++ release and PKC activity) (Calo L et al, Kidney Int, 60:882-889, 2001). BS/GS have also signs that Agn II long term signaling pathway, which contributes to determine cardiovascular remodeling and atherogenesis mostly through oxidative stress, is altered (reduced gene expression of p22phox,key subunit of NAD(P)H oxidase for O2- production, and TGFβ, fibrogenic cytokine effector of oxidative stress, reduced susceptibility of LDL to oxidation, increased plasma antioxidant power) (Calo L et al, JASN, 12:587A, 2001). We now evaluate in our cohort of 9 BS/GS patients, Rho kinase gene expression (RT-PCR expressed as densitometric units (d.u.) using β actin for normalization) as well as gene expression of Rac 2, member of the Rho family monomeric G protein, cytosolic subunit of NAD(P)H oxidase and the Ang II effect on p22phox, TGFβ and PAI-1 gene expression, given PAI-1's link to both Rho kinase activity and atherosclerosis and the close relationships between Rho kinase, Ang II, Rac, p22phox and NAD(P)H oxidase. 10 healthy age and sex matched subjects were used as controls (C). In BS/GS Rho kinase gene expression was reduced compared to C (0.47±0.11 d.u. vs 0.7±0.04, p<0.003) as well as Rac 2 (0.59±0.11 vs 0.75±0.07, p<0.03).Ang II icreased p22phox, TGFβ and PAI-1 gene expression only in controls (from 0.43±0.04 to 0.46±0.05, n.s. in BS/GS vs 0.59±0.12 to 0.96±0.12, p<0.001 in C, from 0.76±0.07 to 0.78±0.05 n.s. vs 0.97±0.11 to 1.27±0.22 p<0.001 and from 0.39±0.01 to 0.39±0.02 n.s. vs 0.4±0.02 to 0.63±0.03, p<0.001 respectively. These data and our previous observations, add more light on the cellular mechanisms of BS/GS reduced Ang II short and long term signaling pathways and, since BS/GS represent the mirror image of derangements involved in hypertension, confirm BS/GS as a human model to study interrelated systems involved in the pathophysiology of hypertension and remodeling.