Insights into the Angiotensin II (Ang II) signalling pathways have been provided by extensive studies using Bartter's/Gitelman's syndromes patients. These syndromes are characterized by activation of the renin-angiotensin-aldosterone system but do not develop hypertension and cardiovascular remodelling, therefore represent a mirror image of hypertension and clinically manifest themselves as the opposite of hypertension. The short and the long-term signalling of Ang II remain an important matter of investigation to shed light on mechanisms responsible for the pathophysiology of hypertension and its long-term complications, such as cardiovascular remodelling and atherogenesis. In particular the long-term signalling of Ang II is involved in the pathophysiology of cardiovascular-renal remodelling, inflammatory and hypertrophic responses in which the relationship between RhoA/Rho kinase pathway and NO system plays a crucial role. This review reports the results of our studies in Bartter's and Gitelman's syndromes to get better insight these processes and the role of Ang II signaling. The information obtained from the studies in Bartter's/Gitelman's patients can, in fact, clarify, confirm or be used to gather more general data on the biochemical mechanisms responsible for the pathophysiology of hypertension and its long-term complications and could contribute to identify additional potential significant targets of therapy.