On the contrary Ocaranza et al. [78] showed that by inhibiting the RhoA/Rho-kinase pathway with fasudil, gene expression and enzymatic ACE activity and plasma levels of Ang II were reduced ( Figure 2 ) and whereas aortic gene expression and ACE2 activity were importantly increased. Simultaneously, plasma levels of Ang-(1-9) (Figure 2 ), mRNA eNOS levels increased and the aortic overexpression of the remodeling promotion proteins TGF-β1, PAI-1, and MCP-1 as well as the increased aortic NADPH oxidase activity and O 2− production were reduced, as a consequence of direct RhoA/Rho-kinase inhibition [100] . This novel effect of RhoA/Rho-kinase inhibition on ACE2 gene expression, enzymatic activity, and Ang-(1-9) levels might additionally contribute to its benefits in hypertension, atherosclerosis, and in cardiovascular and renal pathologic remodeling. This is the first observation concerning a pharmacologic ACE2 and Ang-(1-9) levels activator, both in normotensive and in hypertensive animals, one of the most interesting findings of that study (Figure 2 ). Additionally, in experimental hypertension, direct RhoA/Rho-kinase inhibition also normalizes overexpression of genes that promote vascular remodeling. Interestingly, the observed changes in ACE/ACE2 and in Ang-(1-9) levels were present only during fasudil treatment both in sham and in the DOCA hypertensive rats [78] . Thus, vascular remodeling could be more dependent on the tissue ACE2/Ang-(1-9) axis than on Ang-(1-7) levels in normotensive as well as in hypertensive rats.