Towards an integrated approach on RAAS-blockade

The role of the RAAS in cardiovascular and renal disease is much more complicated than initially assumed. Whereas blockade of the system by ACEi or AT-1 blockade has turned out to be one of the most effective therapies in prevention and treatment of cardiovascular and renal disease, still in many patients the response to therapy is insufficient to prevent ongoing cardiovascular and renal damage. This warrants further exploration of the mechanisms underlying progressive target organ damage and the response to RAAS-blockade. The increasing knowledge on both genetic and environmental factors influencing the RAAS and the response to intervention will hopefully improve the individual therapeutic efficacy in the future. This thesis demonstrates the pleiotropic diversity of the system and provides clues to strategies to improve and target individual therapy response. Further exploration of the role of ACE2 and ang 1-7 may allow making better use of the protective properties of the RAAS by the ACE2-ang 1-7 -mas-receptor axis. Manipulation of sodium status can be used as a tool to orchestrate the pleiotropic effects of RAAS-blockade, as during high sodium intake effects on adiponectin become apparent. The other way round, sodium restriction can be used as a tool to circumvent resistance to ACEi in the DD genotype. It is fascinating that after more than a century of research on the RAAS we are still getting better insights in the (patho-) physiology of the system, thus further increasing the window of opportunity for improving the therapeutic efficacy of RAAS-blockade.